CT-based CTVHR for cervical brachytherapy

Our purpose was to develop recommendations for contouring the computed tomography (CT)-based high-risk clinical target volume (CTVHR) for 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. A 15-member Japanese Radiation Oncology Study Group (JROSG) committee with expertise in gynecological radiation oncology initiated guideline development for CT-based CTVHR (based on a comprehensive literature review as well as clinical experience) in July 2014. Extensive discussions occurred during four face-to-face meetings and frequent email communication until a consensus was reached. The CT-based CTVHR boundaries were defined by each anatomical plane (cranial–caudal, lateral, or anterior–posterior) with or without tumor progression beyond the uterine cervix at diagnosis. Since the availability of magnetic resonance imaging (MRI) with applicator insertion for 3D planning is currently limited, T2-weighted MRI obtained at diagnosis and just before brachytherapy without applicator insertion was used as a reference for accurately estimating the tumor size and topography. Furthermore, utilizing information from clinical examinations performed both at diagnosis and brachytherapy is strongly recommended. In conclusion, these recommendations will serve as a brachytherapy protocol to be used at institutions with limited availability of MRI for 3D treatment planning

QOL after RT or OP for uterine cervix cancer

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important

Insufficiency Fractures after Pelvic Radiotherapy for Uterine Cervical Cancer: An Analysis of Subjects in a Prospective Multi-institutional Trial, and Cooperative Study of Japan Radiation Oncology Group (JAROG) and Japanese Radiation Oncology Study Group (JROSG)

Purpose/Objective(s): To investigate the pelvic insufficiency fractures (IF) post definitive pelvic radiotherapy for early stage uterine cervicalcancer, we analyzed the subject in a prospective multi-institutional study (JAROG0401/ JROSG04-2).\nMaterials/Methods: Between September 2004 and July 2007, 59 eligible patients, all Japanese, were enrolled. Median age was 73 years (range:37-84 years). The eligible patients had squamous cell carcinoma of the uterine cervix, and FIGO stages were Ib1: 35, IIa: 12, IIb: 12, and no pelvic/paraaortic lymphadenopathy. Protocol treatment consisted of whole pelvic external beam radiotherapy of 50 Gy/25 fractions and high-dose-rate intracavitary brachytherapy of 24 Gy/4 fractions (at point A) without chemotherapy. After radiotherapy, the patients were evaluated by both pelvic CT and pelvic MRI at 3, 6, 12, 18, and 24 months. Diagnosis of the IF was made when the patients had both CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. CT findings of IF were defined as fracture lines or sclerotic linear changes in the bones, and MRI findings of IF were defined as the signal intensity changes in the bones, both on T1 and T2 weighted images. The patients also evaluated by CTCAE (Common Terminology Criteria for Adverse Events)-v.3.0 every 3months from 3 until 30 months.\nResults: Median follow-up was 24 months (range: 3-30 months). The 2-year pelvic IF cumulative occurrence rate was 36% (21pts). On CTCAE-v3.0, G1, G2 and G3 were seen in 12 pts (20%), 6 pts (10%), and 3 pts (5%), respectively. Sixteen patients had multiple fractures, so the IF were identified at 44 sites. The pelvic IF were frequently seen at the ileo-cecal joints (32 sites: 72%),and at the pubes (9 sites: 20%). Nine patients complained of pelvic or back pains. All patients\u27 pains were palliated by non-narcotic analgesic drugs.No patients needed surgical intervention. The higher age (>70y) was thought to be a risk factor of pelvic IF (p=0.03, log-rank test).\nConclusions: Older cervical cancer patients received pelvic radiotherapy may have some risks to develop pelvic IF. However, less than a half of the patients with IF complained of pains, and the pains caused by IF were treated effectively by non-narcotic analgesic drugs.52nd ASTRO Annual meetin

Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease

Abstract Steatotic liver disease (SLD) is a burgeoning health problem predominantly associated with excessive alcohol consumption, which causes alcohol-related liver disease (ALD), and high caloric intake, which results in metabolic dysfunction-associated SLD (MASLD). The pathogenesis of ALD and MASLD, which can progress from steatohepatitis to more severe conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma, is complicated by several factors. Recently, extracellular ATP and adenosine (Ado), as damage-associated molecular patterns, were reported to promote inflammation and liver fibrosis, contributing to SLD pathogenesis. Here, we explored the in vivo dynamics of hepatic extracellular ATP and Ado during the progression of steatohepatitis using a genetically encoded GPCR-activation-based sensor (GRAB) in zebrafish models. We established hepatocyte-specific GRABATP and GRABAdo in zebrafish and investigated the changes in in vivo hepatic extracellular ATP and Ado levels under ALD or MASLD conditions. Disease-specific changes in hepatocyte extracellular ATP and Ado levels were observed, clearly indicating a correlation between hepatocyte extracellular ATP/Ado dynamics and disease progression. Furthermore, clodronate, a vesicular nucleotide transporter inhibitor, alleviated the MASLD phenotype by reducing the hepatic extracellular ATP and Ado content. These findings provide deep insights into extracellular ATP/Ado dynamics in disease progression, suggesting therapeutic potential for ALD and MASLD