OBJECTIVE: We report on a case of locally advanced hepatocellular carcinoma (HCC) accompanied by an inferior vena cava tumor thrombus (IVCTT), treated successfully with proton-beam therapy (PBT).
METHODS: A 63-year-old male presented with a primary, single HCC with IVCTT, without metastasis to the intrahepatic region, lymph nodes, or distant organs. The clinical staging was identified as T4N0M0 Stage IIIB. The patient\'s liver function was classified as Child-Pugh class A (score: 6), with a modified albumin-bilirubin (mALBI) grade of 2a. The patient had liver cirrhosis due to non-alcoholic steatohepatitis. Magnetic resonance imaging revealed a nodular tumor measuring 13.2×8.9×9.8 cm across segments 1, 6, 7, and 8, along with IVCTT. The patient received PBT, with a total dose of 72.6 Gy (relative biological effectiveness) delivered in 22 fractions. Throughout the PBT treatment, the patient experienced no acute toxicities and completed the therapy as planned. Twelve months following PBT, the patient was alive without evidence of local recurrence, lymph node involvement, or distant organ metastasis. The only late toxicity observed was a mild worsening of the mALBI grade.
CONCLUSIONS: We observed a favorable local response with manageable toxicities in a patient with locally advanced HCC and IVCTT treated with PBT. While this is a single case report, our findings suggest that PBT could be considered a viable treatment option for HCC with IVCTT.

BACKGROUND: Ocular surface disorder after ocular radiation therapy, even though commonly reported, is often overlooked. Any delay in diagnosis may lead to complications that threaten vision. The presented case highlights the clinical outcome of a severe post-radiation disorder of the ocular surface, the importance of intensive therapy, and the limitations of further surgical interventions.
METHODS: A 34-year-old woman was referred for a second opinion due to a years-long history of pain and redness in her right eye (OD) after proton beam therapy for recurrent iris melanoma. The patient then developed post-radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted, including phacoemulsification with IOL implantation and trabeculectomy with mitomycin C. Due to refractory glaucoma, Baerveldt glaucoma drainage was then necessary. Given the worsening clinical presentation of post-radiation ocular surface disorder with progressing band keratopathy, the possibility of penetrating keratoplasty (PKP) was discussed.
CONCLUSIONS: The continuous worsening of clinical symptoms of the disorder of the ocular surface after proton beam radiotherapy can be the result of a post-radiation syndrome. Gradual expansion of ischemia, vasculitis, and inflammatory mediators compresses the retinal tissue, leading to recurrent macular edema as well as to secondary glaucoma and corneal decompensation. Band keratopathy is occasionally noted and seems to result from severe post-radiation disorder of the ocular surface. However, PKP would typically be indicated in cases of corneal perforation, uncontrolled infectious keratitis, or for improving vision in the presence of corneal opacification, none of which applied to our patient. Furthermore, post-radiation keratopathy implies compromised corneal stromal lymphogenesis and angiogenesis, both of which are now considered essential conditions for allograft rejection. Moreover, a previously performed Baerveldt glaucoma drainage surgery can affect the survival rate of the endothelial cells of the recipient cornea. Therefore, a penetrating or endothelial keratoplasty should be viewed as a high-risk procedure. In this instance, the rigorous treatment of the severe ocular surface disorder was crucial. We managed our patient\'s complex situation by following the latest guidelines set by the Tear Film & Ocular Surface Society and aimed to alleviate the symptoms as effectively as possible. In conclusion, careful decision-making regarding surgical treatment options should be considered, taking into account the complexities and potential risks involved.
Eine 34-jährige Frau wurde wegen Schmerzen und Rötungen am rechten Auge seit Jahren überwiesen. Ihre Krankengeschichte ergab eine Exzision eines Irismelanoms im Alter von 29 Jahren. Aufgrund eines Rezidivs wurde daraufhin eine Protonenstrahlentherapie durchgeführt. Infolgedessen entwickelte die Patientin nach der Strahlentherapie eine Retinopathie mit Makulaödem, sekundärem Glaukom, Katarakt sowie einer schweren Störung der Augenoberfläche mit Hornhautdekompensation und einer Bandkeratopathie. Es wurden mehrere chirurgische Eingriffe unternommen, darunter die Phakoemulsifikation mit IOL-Implantation und die Trabekulektomie mit Mitomycin C. Aufgrund des refraktären Glaukoms war schließlich auch eine Baerveldt-Implantation erforderlich. Trotz vielfältiger therapeutischer Ansätzen zur Befeuchtung zeigte sich keine Verbesserung des Problems der Augenoberfläche. Aufgrund der Verschlechterung der klinischen Präsentation der Augenoberflächenstörung wurde die Möglichkeit einer perforierenden Keratoplastik in Betracht gezogen. Es bleibt jedoch fraglich, ob solche Patienten von einer perforierenden Keratoplastik profitieren würden, da die resultierende Lymph- und Hämangiogenese des Hornhautstromas wesentliche Risikofaktoren für die Abstoßung von Fremdgewebe darstellen.

BACKGROUND: Atezolizumab/bevacizumab combination therapy became the first-line therapy for advanced hepatocellular carcinoma (HCC). Gastroesophageal varices should be monitored and managed before treatment. The progression of portal hypertension during bevacizumab-containing therapy is unclear.
METHODS: A case of new development of esophageal varices, ascites, and hepatic hydrothorax during atezolizumab/bevacizumab therapy at National Taiwan University Hospital was reported, and relevant literature was reviewed.
RESULTS: We presented an 83-year-old male with resolved hepatitis B without cirrhosis. He had BCLC stage C HCC and received tri-weekly atezolizumab/bevacizumab therapy for 34 cycles with sustained partial response. Progressive ascites, esophageal varices, and hepatic hydrothorax developed, though his portal vein was patent and the tumor was under control. Five similar cases of HCC (BCLC B/C: n = 3/2) had been reported previously. Among them, three had cirrhosis with pre-existing small esophageal varices before treatment. After the administration of 1-15 cycles of atezolizumab/bevacizumab therapy, one patient had a progression of varices, and the other four developed variceal bleeding. The association between atezolizumab/bevacizumab and portal hypertension was possible, which might relate to the VEGF pathway and immune-related adverse events with progressive hepatic fibrosis.
CONCLUSIONS: Atezolizumab/bevacizumab treatment might exacerbate portal hypertension. Careful monitoring and management should be considered during treatment.

The development of effective treatment strategies for unresectable retroperitoneal sarcoma is desirable. Herein, we suggest that definitive proton therapy (PT) could be a promising treatment option, regardless of the large size of the tumor. A 52-year-old man presented with a discomfort of the lower abdomen. Computed tomography revealed a retroperitoneal tumor, measuring over 20 cm in the largest dimensions, which was surrounded by the gastrointestinal (GI) tract. Biopsy revealed dedifferentiated liposarcoma. Neoadjuvant chemotherapy was ineffective, and the tumor was ultimately deemed unresectable. The patient opted to receive PT instead of continuation of chemotherapy. Spot scanning PT (SSPT) at a total dose of 60.8 Gy (relative biological effectiveness) in 16 fractions was employed. SSPT administered a dose to the tumor while successfully sparing the surrounding GI tract. He did not receive any maintenance systemic therapy after PT. The tumor gradually shrunk over more than 7 years, with no evidence of recurrence outside the irradiation field. The initial measurable tumor volume of 2925 cc decreased to 214 cc at the final follow-up, seven and a half years after PT. The patient is alive without any severe complications.

We report our early clinical experience with image-guided, pencil beam scanning proton beam therapy (PBS-PBT) for residual and recurrent craniopharyngioma.
Between September 2019 and January 2023, 19 consecutive patients with residual or recurrent craniopharyngioma, suitable for radiotherapy and treated with image-guided PBS-PBT were analyzed. We documented detailed dosimetric data, acute toxicities, early outcomes, and imaging response on follow-up magnetic resonance imaging scans.
A total of 19 patients (11 males and 8 females) with residual or recurrent craniopharyngioma were treated during the study period. The median age of the cohort was 14 years (range, 3-33 years). The histology of most lesions was the adamantinomatous subtype (95%). The most common clinical presentation (before PBT) and most common endocrine deficit was visual disturbance (79%) and hypocortisolism (74%), respectively. Of the 19 patients, 13 had recurrent craniopharyngioma, and 5 had undergone radiotherapy previously. Five patients (26%) had undergone surgery ≥3 times before proton therapy. The median dose delivered was 54 GyE. The most common acute toxicity was grade 1 alopecia (63%). No patient experienced grade ≥3 acute toxicity. With a median follow-up of 18 months (range, 3-40 months), 12 patients showed shrinkage of the residual tumor and/or cyst, and 4 showed a dramatic cyst reduction at 3-9 months of follow-up. Two patients experienced a reduction in both solid and cystic components, with the remaining experiencing a reduction in the cystic component only. The remaining 8 patients had stable disease on magnetic resonance imaging, with 100% disease control and overall survival. Visual function remained stable after treatment.
Our preliminary experience with modern PBS-PBT and image guidance for craniopharyngioma is encouraging. Proton therapy in our cohort was well tolerated, resulting in limited toxicity and promising early outcomes.

Chemotherapy is the standard therapy for unresectable intrahepatic cholangiocarcinoma(ICC), but chemotherapy is not efficacious. Proton beam therapy(PBT)has been covered by Japanese health insurance for ICC since 2022, and the number of cases is expected to increase. In some cases, irradiation is difficult due to the close proximity of the gastrointestinal tract to the tumor. We report our management of a patient with ICC close to the gastrointestinal tract. The patient was a 69-year- old woman with a history of distal gastrectomy and Billroth-Ⅰ reconstruction for gastric cancer. A CT scan showed a tumor in liver S3; a biopsy revealed ICC. Because the tumor was in contact with the gastroduodenal anastomosis, we placed an absorbable spacer and performed PBT. After the treatment, the tumor shrank slightly. Although the liver is anatomically adjacent to the digestive tract, the placement of absorbable spacers facilitates performing PBT without adverse events, and is thus considered a useful treatment.

This Viewpoint present the case for revisiting the proscription of proton beam therapy in trials of patients with de novo, nonmetastatic head and neck cancer.

Solitary fibrous tumor (SFT) of the central nervous system is a rare fibroblastic tumor of mesenchymal origin. SFTs in the saddle area are much less common. In January 2022, a 43-year-old female patient was admitted with SFT 3 months following partial resection of a microscopic transsphenoidal saddle area tumor at a different hospital. Magnetic resonance imaging indicated that the unresected part of the tumor was significantly enhanced on T1 enhancement, which strongly indicated a recurrence. Subsequently, the patient underwent transnasal endoscopic saddle area tumor resection at our hospital and the tumor was successfully removed. By using postoperative pathology examination, immunohistochemical analysis of Bcl-2, cluster of differentiation 99, STAT6 and vimentin, and a fusion gene test performed by high-throughput sequencing technology, the SFT was definitively diagnosed. Following 3 months of follow-up, the patient was found to have tumor recurrence in the cavernous sinus and absence of tumor growth in the pituitary fossa. Therefore, the patient received proton therapy and tumor growth was controlled effectively.

We report two cases of pacemaker malfunction occurring during proton beam therapy (PBT) for localized prostate cancer treatment. The first case involved mode changes in the pacemaker, while the second exhibited prolongation of the RR interval. Remarkably, both cases did not manifest significant clinical changes. Our findings indicate that careful consideration should be given to passive PBT in patients with localized prostate cancer who have pacemakers, like the considerations in patients with thoracic and abdominal cancers. Moreover, our report highlights the importance of recognizing potential cardiac implantable electronic devices malfunction in various PBT scenarios.

Hearing loss (HL) is one of the most common complications of the treatment in head and neck oncology. Most cases of HL are due to the ototoxicity of platinum-based chemotherapy (PBC) - resulting usually in a symmetric bilateral sensorineural hearing loss (SNHL) - or radiotherapy. Radiation-induced SNHL is progressive, permanent, and dose-dependent. Total dose and follow-up time are important factors affecting incidence rates. However, the hearing consequences of proton radiation therapy (PRT), a radiation-type therapy especially used in pediatric malignancies of the central nervous system (CNS), remains unclear and poorly documented. We report here a case of a four-year-old patient with unilateral auditory neuropathy spectrum disorder (ANSD) related to PRT. This case highlights the need for appropriate auditory monitoring in patients undergoing PRT for CNS or head and neck malignancies.