Tomoyasu Kumano

Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication

The Rad17‐replication factor C (Rad17‐RFC) and Rad9‐Rad1‐Hus1 complexes are thought to function in the early phase of cell‐cycle checkpoint control as sensors for genome damage and genome replication errors. However, genetic analysis of the functions of these complexes in vertebrates is complicated by the lethality of these gene disruptions in embryonic mouse cells. We disrupted the Rad17 and Rad9 loci by gene targeting in the chicken B lymphocyte line DT40. Rad17−/− and Rad9−/− DT40 cells are viable, and are highly sensitive to UV irradiation, alkylating agents, and DNA replication inhibitors, such as hydroxyurea. We further found that Rad17−/− and Rad9−/− but not ATM−/− cells are defective in S‐phase DNA damage checkpoint controls and in the cellular response to stalled DNA replication. These results indicate a critical role for chicken Rad17 and Rad9 in the cellular response to stalled DNA replication and DNA damage.

Feeding artery of laryngeal and hypopharyngeal cancers: role of the superior thyroid artery in superselective intraarterial chemotherapy.

The purpose of this study was to elucidate the role of the superior thyroid artery in intra-arterial infusion chemotherapy for laryngeal and hypopharyngeal cancers. Thirty-nine patients with laryngeal cancer and 29 patients with hypopharyngeal cancer underwent intra-arterial infusion chemotherapy. We performed a retrospective analysis of the feeding arteries confirmed by computed tomography during selective arteriography and compared the results with the extent of the tumors. In 14 of 39 laryngeal and 15 of 29 hypopharyngeal cancers, the tumor did not cross the midline (group 1). In the remaining 25 and 14 cancers, respectively, the tumor crossed the midline or located in the center (group 2). For 13 of 14 laryngeal and 7 of 15 hypopharyngeal cancers in group 1 and for 6 of 25 laryngeal cancers in group 2, the entire tumor was contrast enhanced by the ipsilateral superior thyroid and/or superior laryngeal artery. For 12 of 25 laryngeal and 1 of 14 hypopharyngeal cancers in group 2, the entire tumor was contrast enhanced by the bilateral superior thyroid artery. For the other patients, infusion via the other arterial branches such as the inferior thyroid and the lingual arteries were needed to achieve contrast enhancement of the entire tumor. Superselective intra-arterial chemotherapy for laryngeal cancer from the superior thyroid artery is appropriate, whereas that for hypopharyngeal cancer is less sufficient. To accomplish contrast enhancement of the entire tumor, additional intra-arterial infusion from other arteries such as the inferior thyroid artery is often necessary.

Basaloid squamous cell carcinoma in the nasal cavity treated with proton beam therapy concurrent with cisplatin: a case report.

IntroductionBasaloid squamous cell carcinoma is a rare and aggressive variant of squamous cell carcinoma. Basaloid squamous cell carcinoma is mostly seen in the upper aerodigestive tract and has a propensity for lymph node spread and systemic metastases. Various treatment modalities have been reported, including surgical excision supplemented with radiotherapy/adjuvant chemotherapy. To the best of our knowledge, treatment of nasal basaloid squamous cell carcinoma with proton beam therapy and cisplatin has not been described in the literature.Case presentationWe report the case of a 56-year-old Japanese man with locally invasive basaloid squamous cell carcinoma in his right nasal cavity with invasion of the orbit, paranasal sinus, and buccal subcutaneous tissue. He underwent proton beam therapy concurrent with cisplatin. Acute and late side effects did not exceed grade 3. At 24-month follow up, he remains in complete remission.ConclusionProton beam therapy concurrent with cisplatin may be one choice for locally invasive basaloid squamous cell carcinoma.

Accuracy of Dose Delivery in Multiple Breath-Hold Segmented Volumetric Modulated Arc Therapy: A Static Phantom Study

Purpose. Accuracy of dose delivery in multiple breath-hold segmented volumetric modulated arc therapy (VMAT) was evaluated in comparison to noninterrupted VMAT using a static phantom. Material and Methods. Five VMAT plans were evaluated. A Synergy linear accelerator (Elekta AB, Stockholm, Sweden) was employed. A VMAT delivery sequence was divided into multiple segments according to each of the predefined breath-hold periods (10, 15, 20, 30, and 40 seconds). The segmented VMAT delivery was compared to noninterrupted VMAT delivery in terms of the isocenter dose and pass rates of a dose difference of 1% with a dose threshold of 10% of the maximum dose on a central coronal plane using a two-dimensional dosimeter, MatriXX Evolution (IBA Dosimetry, Schwarzenbruck, Germany). Results. Means of the isocenter dose differences were 0.5%, 0.2%, 0.2%, 0.0%, and 0.0% for the beam-on-times between interrupts of 10, 15, 20, 30, and 40 seconds, respectively. Means of the pass rates were 85%, 99.9%, 100%, 100%, and 100% in the same order as the above. Conclusion. Our static phantom study indicated that the multiple breath-hold segmented VMAT maintains stable and accurate dose delivery when the beam-on-time between interrupts is 15 seconds or greater.

Respiratory-Gated Proton Beam Therapy for Hepatocellular Carcinoma Adjacent to the Gastrointestinal Tract without Fiducial Markers

The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has been reported, but insertion of fiducial markers in the liver is usually required. We evaluated the efficacy and toxicity of respiratory-gated PBT without fiducial markers for HCC located within 2 cm of the gastrointestinal tract. From March 2011 to December 2015 at our institution, 40 patients were evaluated (median age, 72 years; range, 38–87 years). All patients underwent PBT at a dose of 60 to 80 cobalt gray equivalents (CGE) in 20 to 38 fractions. The median follow-up period was 19.9 months (range, 1.2–72.3 months). The median tumor size was 36.5 mm (range, 11–124 mm). Kaplan–Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 76%, 60%, and 94%, respectively. One patient (2.5%) developed a grade 3 gastric ulcer and one (2.5%) developed grade 3 ascites retention; none of the remaining patients developed grade >3 toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.0.). This study indicates that PBT without fiducial markers achieves good local control without severe treatment-related toxicity of the gastrointestinal tract for HCC located within 2 cm of the gastrointestinal tract.

Pathology and images of radiation-induced hepatitis: a review article

Recent advances in highly conformal radiotherapies greatly extend the indications for radiotherapy of liver tumors. However, because of poor tolerance to hepatic radiation, estimation of the intensity of irradiation of the liver is important, particularly for a cirrhotic liver. Knowledge of radiation-induced hepatitis is important for understanding how to optimize hepatic radiation therapy. Pathological changes of the irradiated liver, which include perivenular fibrosis, sinusoidal obstruction, and damage to Kupffer cells and hepatocytes, can be visualized using clinical imaging techniques. This review article discusses and illustrates the pathological and radiological changes of hepatic tumors and the surrounding parenchyma of the irradiated liver.

Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas

We evaluated the effectiveness and toxicity of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) >5 cm without fiducial markers using four-dimensional CT (4D-CT) planning. The subjects were 29 patients treated at our hospital between March 2011 and March 2015. The median total dose was 76 Cobalt Gray Equivalents (CGE) in 20 fractions (range; 66–80.5 CGE in 10–32 fractions). Therapy was delivered with end-expiratory phase gating. An internal target volume (ITV) margin was added through the analysis of respiratory movement with 4D-CT. Patient age ranged from 38 to 87 years (median, 71 years). Twenty-four patients were Child–Pugh class A and five patients were class B. Tumor size ranged from 5.0 to 13.9 cm (median, 6.9 cm). The follow-up period ranged from 2 to 72 months (median; 27 months). All patients completed PBT according to the treatment protocol without grade 4 (CTCAE v4.03 (draft v5.0)) or higher adverse effects. The two-year local tumor control (LTC), progression-free survival (PFS), and overall survival (OS) rates were 95%, 22%, and 61%, respectively. The LTC was not inferior to that of previous reports using fiducial markers. Respiratory-gated PBT with 4D-CT planning without fiducial markers is a less invasive and equally effective treatment for large HCCs as PBT with fiducial markers.