References
fever, toxicities, Cancer, Tumor, toxicity, thrombocytopenia, rash, bullous formationGrade, hepatitis, peripheral neuromotor syndrome, diarrhea, anemia, neurotoxicity, nephritis, cholestasis, colitis, pneumonitis, neutropenia, respiratory insufficiency, myocarditis, immune-mediated AE, immune-mediated neurotoxicity, diarrhea/colitis, Sjogren’s syndrome
ENDOCRINOPATHIES, ONCOLOGY, CANCER, TUMOR, ADVERSE EVENT, THROMBOCYTOPENIA, IMMUNE-MEDIATED MYOCARDITIS, HEPATITIS, GUILLAIN-BARRÉ, ANEMIA, MYASTHENIA GRAVIS, NEPHRITIS, ADVERSE EVENT, CHOLESTASIS, COLITIS, PNEUMONITIS, DISEASE PROGRESSION, METASTASIS, NEUTROPENIA, EVENT, RESPIRATORY INSUFFICIENCY, MYOCARDITIS, VIRAL HEPATITIS
Representative images of the patients who received the treatment. (Design of the present study. C-ion RT = carbon-ion radiotherapy; DLT = dose-limiting toxicity; CT = computed tomography; MRI = magnetic resonance imaging.The clinical characteristics of the three patients.ECOG PS = Eastern Cooperative Oncology Group performance status; FIGO = the International Federation of Gynecology and Obstetrics; TNM = Tumor, node, and metastasis; UICC = Union for International Cancer Control; NOS = not otherwise specified.Adverse events (possibly, probably, or definitely) attributed to the treatment.GGT = gamma-glutamyl transpeptidase. * This patient was diagnosed with Sjogren’s syndrome.The dose-limiting toxicities of the present study.Grade ≥ 3 neutropenia complicated by fever ≥ 38.3 °CGrade 4 neutropenia (≥7 days)Grade ≥ 3 thrombocytopenia with significant bleedingGrade 4 thrombocytopenia (regardless of duration)Grade 4 anemia (regardless of duration)Any Grade 4 non-immune-mediated AEAny Grade 4 immune-mediated AE, excluding endocrinopathiesAny Grade 3 non-immune mediated AE that does not resolve to ≤Grade 1 or baseline within 30 days with optimal medical managementAny Grade 3 immune-mediated AE—excluding diarrhea/colitis, pneumonitis, hepatitis, rash, neurotoxicity, myocarditis, myositis/polymyositis, endocrinopathies, and nephritis—that does not resolve to ≤Grade 1 or baseline within 30 days after onset of the event despite optimal medical management including systemic corticosteroidsGrade 3 diarrhea or colitis that does not resolve to ≤Grade 1 within 14 days [both immune- and non-immune-mediated indicated here; the same is the case if not specified in the remaining bullet points below]Grade 3 non-infectious pneumonitisGrade 2 non-infectious pneumonitis that does not resolve to ≤Grade 1 within 3 days of the initiation of maximal supportive careAST or ALT ≥ 3 × ULN with a concurrent increase in TBL ≥ 2 × ULN without evidence of cholestasis or alternative explanations (e.g., viral hepatitis, disease progression in the liver, i.e., “Hy’s Law”)ALT or AST > 8 × ULN or TBL > 5 × ULNGrade 3 immune-mediated rash that does not resolve to ≤Grade 1 or baseline within 30 daysGrade 2 rash covering > 30% BSA that does not resolve to ≤Grade 1 or baseline within 30 daysAny grade of immune-mediated rash with bullous formationGrade 3 immune-mediated neurotoxicity (excluding Guillain-Barre and myasthenia gravis) that does not resolve to ≤Grade 1 within 30 daysGrade 2 or 3 immune-mediated peripheral neuromotor syndrome (such as Guillain-Barre and myasthenia gravis) that does not resolve to ≤Grade 1 within 30 days or that exhibits signs of respiratory insufficiency or autonomic instabilityGrade 3 immune-mediated myocarditisAny symptomatic immune-mediated myocarditis that does not become asymptomatic within 3 days of initiating optimal medical management, including systemic corticosteroidsGrade 2 or 3 immune-mediated myositis/polymyositis that does not resolve to Grade ≤ 1 within 30 days of initiating optimal medical management, including systemic corticosteroids, or that exhibits signs of respiratory insufficiency regardless of optimal medical managementImmune-mediated increase in creatinine >3 × ULN, or >3 × baseline for patients with a baseline creatinine elevated above ULNAE = adverse event; AST = aspartate aminotransferase; ALT = alanine aminotransferase; UNL = upper limit of normal; TBL = total bilirubin; BSA = Body surface area.