Treatment selection for patients with polycythemia vera (PV) is based on patient age and history of thrombosis. The standard treatment is low-dose aspirin and phlebotomy, with cytoreductive therapy added for high-risk PV. Clinical trials in patients with PV have shown that ropeginterferon alfa-2b (ropeg-IFN) treatment is safe, efficacious, and reduces JAK2 V617F allele burden. As PV mainly affects individuals aged 60 years and older, incidence estimates have been increasing. Here we report 3 cases of elderly patients treated with ropeg-IFN who experienced no serious adverse events. All 3 patients achieved and maintained complete hematologic response with reduced JAK2 V617F allele burden. Ropeg-IFN is an effective and safe therapy for elderly patients with PV that also improves quality of life.

Ropeginterferon alfa-2b (ropeg-IFN), a treatment that allows for prolonged dosing intervals through site-specific PEGylation, has been approved for the treatment of polycythemia vera (PV) in patients for whom existing therapies are insufficient or unsuitable. In this case report, we describe a woman in her thirties who was treated with ropeg-IFN. Blood tests showed increased levels of all three blood cell lineages, and PV was diagnosed following bone marrow examination. The patient was enrolled in a clinical study in which she received ropeg-IFN because phlebotomy could not be performed due to difficulty with securing peripheral vascular access. Complete hematologic response (CHR) was achieved 12 weeks after the start of administration, and molecular response (MR) with a JAK2 V617F allele burden of <1% was achieved after approximately 156 weeks of continuous administration of ropeg-IFN. Alopecia (grade 1) occurred as an adverse event, but resolved after ropeg-IFN dose reduction. The patient maintained CHR and MR for 2 years following treatment discontinuation. We also discuss the potential benefit of ropeg-IFN in low-risk PV patients who were not previously considered candidates for aggressive cytoreductive therapy.

We report two cases of polycythemia vera (PV) treated with ropeginterferon alfa-2b (ropeg-IFN) in which hematologic control was maintained without therapy after treatment discontinuation. The patients achieved complete response (CR) at 14 and 22 weeks after treatment initiation, respectively. After discontinuation of ropeg-IFN, Patient 1 has maintained hematocrit (Ht) <45% for 3 years and 3 months, while patient 2 has maintained CR for 1 year and 5 months. Clinical trials have demonstrated that ropeg-IFN reduces the JAK2 V617F allele burden, which is recognized as an independent risk factor for disease progression and thrombosis, apart from traditional factors such as age and prior cardiovascular events. To improve the prognosis of PV, it is essential to accumulate clinical evidence on trends in JAK2 V617F allele burden and the conditions required to maintain hematologic control after discontinuation of ropeg-IFN therapy in real-world settings.

A 19-year-old male patient with abdominal pain and diarrhea was presented to our hospital. He was diagnosed with advanced colorectal cancer based on imaging. Lynch syndrome was suspected, considering his family history. After a laparoscopic subtotal colectomy, genetic testing confirmed a pathogenic variant in the MLH1 gene, leading to a definitive diagnosis of Lynch syndrome. The onset of colorectal cancer is extremely rare in the teenage years. Herein, we discuss the potential involvement of genetic anticipation, emphasize the importance of early surveillance in individuals at risk, and consider the use of multidisciplinary collaboration in providing comprehensive physical and psychological support.

Tyrosine kinase inhibitors (TKIs) have markedly improved the prognosis of chronic myeloid leukemia (CML). In Japan, in addition to the four established first-line TKIs, asciminib is now approved as an initial therapy, expanding the treatment options. Nevertheless, more than 10% of patients treated with asciminib over 48 weeks, and approximately 20-30% of those receiving other TKIs over five years, require second-line therapy because of resistance or intolerance. As first-line choices diversify, selecting the optimal second-line regimen has become increasingly complex. For intolerance, switching should be guided by the adverse-event profile with attention to potential cross-intolerance. For resistance, assessment of BCR::ABL1 mutations is essential, and second-line agents should be chosen according to the initial TKI and mutation sensitivity. This article summarizes the criteria and timing for switching to second-line therapy and key considerations for selecting and managing second-line TKIs, and briefly reviews the evidence for asciminib and ponatinib in second-line and later settings.

A 52‒year‒old female with gastric cancer revealed by a medical examination. The patient was diagnosed with T4b(pancreas)N2M0, CY0P0, cStage ⅣA, and after 3 courses of docetaxel+oxaliplatin+S‒1(DOS)therapy as preoperative chemotherapy, laparoscopic distal gastrectomy with D2 lymph node dissection and Roux‒en‒Y reconstruction were performed. Pathological histological examination showed ypT3(SS)N2M1(CY+), Stage Ⅳ, HER2(-), and S‒1+oxaliplatin(SOX)therapy was initiated as first‒line treatment. Tumor markers elevated and CT scan showed ascites after 5 courses and the treatment was consequently changed to paclitaxel+ramucirumab(PTX+Ram)therapy as second‒line treatment. CT scan showed para‒aortic lymph node enlarged and increased ascites after 2 courses, MSI‒High was identified at the same time and the treatment was consequently changed to pembrolizumab(Pem)monotherapy(200 mg/body, q21 days)as third‒line treatment. CT scan showed partial response(PR)after 3 courses, and subsequently resulted in a complete response(CR). After 36 courses of Pem monotherapy, the chemotherapy was terminated at the patient's request. Four years after the initial onset, the patient is currently alive without recurrence. No serious adverse events have occurred since the start of Pem monotherapy.

A 70-year-old man with prostate cancer (cT3aN0M0), with a prostate-specific antigen (PSA) level of 38.9 ng/mL, and a Gleason score of 4+4 = 8, was treated with maximum androgen blockade for 1 year, resulting in a PSA reduction to 0.1 ng/mL. He subsequently underwent robot-assisted laparoscopic radical prostatectomy (RARP). Pathological examination revealed pT3bN1with negative surgical margins. Postoperatively, without additional treatment, PSA levels were 0.007 ng/mL and 0.019 ng/mL at 2 and 5 months, respectively. Six months after surgery, the patient developed left hydronephrosis with upper ureteral urine leakage but no signs of ureteral cancer. However, PSA slightly increased to 0.055 ng/mL, whereas carcinoembryonic antigen (CEA) levels increased to 19.2 ng/mL. Despite this, gastro-colonoscopy failed to detect any evidence of cancer. Nine months after surgery, multiple lung tumors, a solitary hepatic tumor, intraperitoneal lymphatic swellings, and port site masses were identified. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan did not reveal any other malignancies. At that time point, PSA increased to 0.185 ng/mL, while neuron-specific enolase and pro-gastrin-releasing peptides levels were within normal limits. Subsequent gastro-colonoscopy did not detect any malignancies. Ten months after surgery, bilateral orchiectomy and docetaxel chemotherapy were initiated for recurrent prostate cancer with aggressive variants but without neuroendocrine differentiation. Immunohistochemistry (IHC) of a biopsy sample from the port site mass suggested enteric adenocarcinoma distinct from the prostatic tissue observed in the original RARP specimen. The metastases progressed, and CEA levels continued to rise despite three cycles of docetaxel chemotherapy. Genomic testing identified KRAS and other mutations, confirming the tumor's compatibility with enteric adenocarcinoma. Fourteen months after surgery, chemotherapy for colon cancer was initiated. Unfortunately, the patient succumbed to respiratory failure 19 months after surgery. In cases of unusual recurrence patterns, as observed in this case, IHC and genomic testing of the recurrent mass can be crucial for accurate diagnosis.

Genetic medicine related to hereditary cancer syndromes has undergone significant changes in recent years. We have summarized the establishment of a genetic medicine treatment system for breast cancer at our institution. From April 2020 to October 2024, there were 11 cases(1.6% of all breast cancer cases)with pathogenic variants in the BRCA1/2 genes. Among all breast cancer patients, there was 1 case of Li-Fraumeni syndrome suspected and the other case of NF1 diagnosed. From January 2020 to October 2024, the comprehensive cancer genome profiling was performed in 23 breast cancer cases, with germline findings identified in CDH1 in 1 case. Genetic testing for asymptomatic relatives and clients with identified germline findings has been established, and Clinical Genomics for outpatients was opened in October 2024. We strive to provide personalized genetic medicine focusing on preventive care for clients and asymptomatic relatives.

We report the case of an 80-year-old man who presented with acute abdominal pain and was emergently hospitalized. Contrast-enhanced computed tomography revealed a tumor in the ascending colon with free intraperitoneal air and ascites, without evidence of distant metastasis. A diagnosis of acute generalized peritonitis due to perforation of an ascending colon tumor was made, and the patient underwent emergency surgery consisting of primary closure of the perforation and creation of a diverting ileostomy. Postoperative colonoscopy identified a tumor in the ascending colon. Histopathological examination of biopsy specimens confirmed adenocarcinoma with HER2 positivity, RAS mutation, and microsatellite instability- high(MSI-high). The clinical stage was cT4bN1bM0(duodenum), Stage Ⅲc. Pembrolizumab therapy was initiated 1 month after surgery. Progressive tumor regression was observed during treatment, and after 14 courses, colonoscopy demonstrated marked tumor shrinkage with persistent severe luminal stenosis. After 17 courses in total, laparoscopic right hemicolectomy and ileostomy closure were performed. Histopathological examination of the resected specimen showed no residual carcinoma. The histological response was classified as Grade 3 corresponding to a pathological complete response(pCR). No adjuvant chemotherapy was administered. At 5 months after the operation, the patient is alive without any recurrence. This case suggests the potential efficacy of pembrolizumab for MSI-high locally advanced colorectal cancer.

The patient is a woman in her 70s. She came to our hospital because of constipation and abdominal pain. An abdominal CT scan showed a sigmoid colon mass and air in the surrounding mesentery, and an ileostomy was constructed based on the diagnosis of intramesenteric perforation of sigmoid colon cancer. Tumor biopsy by colonoscopy revealed a diagnosis of signet-ring-cell carcinoma. After 6 courses of mFOLFOX6 neoadjuvant chemotherapy, the patient underwent laparoscopic sigmoid colon resection and closure of the ileostomy. The final pathological diagnosis was pT4aN2aM0, pStage Ⅲc, RM1, microsatellite instability-high(MSI-H). Six courses of pembrolizumab chemotherapy were administered as adjuvant chemotherapy. Tumor markers have normalized and there are no signs of recurrence. MSI-H colorectal cancer is reported to account for about 10% of all colorectal cancers and signet-ring-cell carcinoma for only 1%. We report this case because it is a rare combination of both and a valuable case of successful multidisciplinary treatment.

To evaluate the impact of a rapid testing workflow for obtaining BRCA genomic test results prior to surgery and multidisciplinary collaboration on surgical treatment selection.

Skin metastasis of colorectal cancer is a rare condition. Herein, we report a case of skin metastasis of MSI-high sigmoid colon cancer to the buttocks. A 41-year-old male who was referred to our hospital for anemia, elevated inflammatory response, weight loss, and hematochezia during his general health examination. Computed tomography(CT)revealed a thickening of the sigmoid colon wall, fistula formation between other parts of the sigmoid colon, and enlarged mesenteric lymph nodes. The patient was suspected of having skin metastasis due to a mass being found in the upper abdominal subcutaneous region and the skin of the buttock. The buttock and abdominal wall tumors were subjected to pathological examination, which revealed adenocarcinoma. The patient was diagnosed with sigmoid colon cancer with skin metastases. The patient developed an intestinal obstruction during the examination and underwent a transverse colostomy. Subsequently, pembrolizumab was initiated as the first-line treatment because of the presence of MSI-high and RAS gene mutations (G12S mutation). CT taken after the fifth course of treatment indicated that the tumor had shrunk.

The patient was a woman in her 60s. She presented to our hospital following a positive fecal occult blood test. Colonoscopy revealed multiple advanced cancers in the transverse and sigmoid colon. A subtotal colectomy was performed, followed by adjuvant chemotherapy with the CAPOX regimen. Ten months after surgery, distant metastases to the lungs and mediastinal lymph nodes were observed. Comprehensive genomic profiling(CGP)revealed a mutation in the MLH1 gene. Next-generation sequencing of DNA derived from peripheral blood leukocytes identified a heterozygous pathogenic variant in the MLH1 gene, resulting in a diagnosis of Lynch syndrome. Treatment with immune checkpoint inhibitors(ipilimumab plus nivolumab)was initiated. After confirming a reduction in the size of the metastatic lesions, maintenance therapy with nivolumab monotherapy was continued. As of 4 years and 3 months post-surgery, tumor shrinkage has been sustained, with no evidence of new malignancies, recurrence, or metastasis. Given the presence of multiple colorectal cancers, a history of gynecologic malignancy, and a family history of gastrointestinal cancers, this case illustrates the importance of early consideration of hereditary tumors and highlights the clinical utility of genomic medicine.

Between January 2020 and November 2024, we retrospectively analyzed the results of mismatch repair protein immunohistochemistry(MMR-IHC)/microsatellite instability(MSI)test, RAS, and BRAF genetic tests in 48 consecutive patients under 50 years of age who underwent primary tumor resection of colorectal cancer. Of these, 35 patients underwent MMR-IHC/ MSI testing, revealing 32 proficient MMR(pMMR)/non-MSI-high and 3 deficient MMR(dMMR)/MSI-high, 2 of whom were diagnosed as having Lynch syndrome. RAS/BRAF testing was performed in 28 patients, identifying 6 with KRAS variants, while no BRAFV600E or KRASG12C were found. The frequencies of dMMR and Lynch syndrome in patients under 50 years old was comparable to our previous report in which testing was conducted as part of research. Our results suggest that in patients under 50 years old(, 1)the utility of BRAF testing as an adjunctive diagnostic tool for Lynch syndrome is limited, and (2)BRAFV600E or KRASG12C was not detected;however, a larger accumulation of cases is necessary.

Oncotype DX is performed to predict prognosis and the added benefit of chemotherapy in hormone receptor-positive, HER2-negative breast cancer, with the goal of individualizing chemotherapy decisions. Here, we report 2 cases of early- stage hormone receptor-positive, HER2-negative breast cancer with lymph node metastases in which the oncotype DX test was performed but yielded inconclusive results. Case 1:A 53-year-old woman was diagnosed with left breast cancer following bloody nipple discharge. She underwent total mastectomy and axillary lymph node dissection. Two positive lymph nodes were identified;however, it was difficult to assess the invasive component of the primary tumor. When oncotype DX was performed, it was deemed inconclusive due to insufficient tumor tissue. Case 2:A 46-year-old woman was diagnosed with right breast cancer during routine follow-up at our department. She underwent total mastectomy and axillary lymph node dissection. Although the primary tumor was widely spread within the breast, assessment of the invasive component was challenging. Three lymph node metastases were identified. Oncotype DX was performed but was judged inconclusive due to insufficient tumor tissue.

BRCA pathogenic sequence variants(PSVs)are believed to enhance local immune responses through the generation of tumor neoantigens, leading to increased tumor-infiltrating lymphocytes(TILs).

Blast crisis (BC) in chronic myelocytic leukemia (CML) typically presents with increased blasts in the bone marrow, showing either myeloid or B-lymphoid phenotypes. We report a rare case of CML-BC with a T/myeloid mixed phenotype localized to the lymph nodes. An 80-year-old woman presented with right axillary lymphadenopathy. PET-CT revealed multiple enlarged lymph nodes. Axillary node biopsy showed proliferation of medium-sized atypical lymphoid-like cells expressing both T-cell and myeloid markers. Both bone marrow and peripheral blood showed no abnormalities. The BCR::ABL1 translocation was detected in both bone marrow and lymph node tissue. Fluorescence in situ hybridization showed positive staining for BCR/ABL1 gene rearrangement. Based on these findings, blast crisis of CML with a T/myeloid mixed phenotype was diagnosed. Following dasatinib therapy, the enlarged nodes regressed. Despite the patient's advanced age, no significant adverse events have been observed during the course of treatment.

KRAS mutations are a major genetic alteration found in approximately 40% of unresectable advanced or recurrent colorectal cancer. KRAS has long been considered an"undruggable"target due to its structural characteristics, but in recent years, inhibitors targeting the KRAS G12C mutant protein have been developed, enabling molecular targeted therapy. Sotorasib is the first KRAS G12C inhibitor to be clinically implemented. Following its approval for non-small cell lung cancer, it has also been approved for chemorefractory metastatic colorectal cancer. In colorectal cancer, combination therapy with a KRAS inhibitor and an anti-EGFR antibody is necessary to suppress the activation of EGFR induced by KRAS inhibition. Currently, it is recommended to confirm the presence of KRAS mutations, including G12C, before initiating first-line therapy. Since sotorasib can be administered based on these results, it is expected to broaden treatment options for colorectal cancer patients harboring the KRAS G12C mutation.

Diffuse intrinsic pontine glioma (DIPG) remains one of the most devastating pediatric central nervous system tumors, with a median survival of approximately 11 months despite decades of research. The identification of histone H3 K27M mutations marked a pivotal moment, leading to major advancements in understanding the molecular and epigenetic characteristics of these tumors. This discovery enabled molecular classification and provided a basis for the development of novel therapeutic strategies. In recent years, clinical trials have investigated molecular targeted agents and epigenetic modulators. Immunotherapeutic approaches, such as CAR-T cell therapy, have shown promising early results, whereas innovative drug delivery techniques, including convection-enhanced delivery and focused ultrasound, aim to overcome the challenges of the blood-brain barrier. Two major international registries, the International DIPG/DMG Registry (IDIPGR) and the European Society for Paediatric Oncology (SIOPE) DIPG/DMG Registry, play crucial roles in collecting comprehensive clinical data across multiple countries. The DIPG-2023 registry study was launched in Japan to collect prospective clinical, radiological, and molecular data systematically and to provide a high-quality external control cohort for future intervention trials. These collaborative efforts highlight a new era of DIPG/DMG research, offering cautious optimism for therapeutic progress in this historically refractory disease.

Recent advances in molecular profiling have transformed pediatric brain tumors management. The use of targeted agents is guided by actionable alterations including the BRAF V600E mutation, NTRK fusions, NF1 pathway activation, and H3 K27M mutation. Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.