Relationship between changes in quality of life and genitourinary toxicity grade after brachytherapy with I-125 alone for localised prostate cancer.

Background: The relationship between the grading of toxicities based on toxicity criteria and longitudinal changes in quality of life (QOL) scores after permanent prostate brachytherapy (PPB) for localized prostate cancer remains unclear. This study aimed to evaluate these relationships. Materials and methods: We assessed 107 patients treated with PPB using Iodine-125 alone from May 2007 to April 2010. Disease-specific QOL scores before PPB and at 1, 3, 6, 12, and 24 months after PPB were retrospectively evaluated with the Expanded Prostate Cancer Index Composite (EPIC), focusing on urinary domains. Toxicities were graded using the Radiation therapy oncology group and the European organization for research and treatment of cancer toxicity criteria. Results: The median follow-up duration was 116 (range 18-148) months. Thirty-four patients (31.8%) developed grade ≥ 2 acute genitourinary (GU) toxicities; six (5.6%) developed grade ≥ 2 late GU toxicities. The general urinary domain score dropped significantly at 1 month (77.1 ± 14.1) post-PPB compared to the baseline score (92.2 ± 8.2), and then gradually returned to the baseline level by 12 months (93.7 ± 8.3) post-PPB. Reductions in the general urinary domain scores, including its subscale scores at 1, 3, and 6-months post-PPB were significantly greater among patients with grade ≥ 2 GU toxicity than among those with grade 0-1 GU toxicity. Changes in urinary domain scores demonstrated a close relationship with acute GU toxicity grades after PPB. Conclusions: Longitudinal assessments of the EPIC QOL scores provided additional information regarding time-course changes in GU toxicities after PPB.

Metabolic characterization of aggressive breast cancer cells exhibiting invasive phenotype: impact of non-cytotoxic doses of 2-DG on diminishing invasiveness.

BACKGROUND: Metabolic reprogramming is being recognized as a fundamental hallmark of cancer, and efforts to identify drugs that can target cancer metabolism are underway. In this study, we used human breast cancer (BC) cell lines and established their invading phenotype (INV) collected from transwell inserts to compare metabolome differences and evaluate prognostic significance of the metabolome in aggressive BC invasiveness. METHODS: The invasiveness of seven human BC cell lines were compared using the transwell invasion assay. Among these, INV was collected from SUM149, which exhibited the highest invasiveness. Levels of metabolites in INV were compared with those of whole cultured SUM149 cells (WCC) using CE-TOFMS. The impact of glycolysis in INV was determined by glucose uptake assay using fluorescent derivative of glucose (2-NBDG), and significance of glycolysis, or tricarboxylic acid cycle (TCA) and electron transport chain (ETC) in the invasive process were further determined in aggressive BC cell lines, SUM149, MDA-MB-231, HCC1937, using invasion assays in the presence or absence of inhibitors of glycolysis, TCA cycle or ETC. RESULTS: SUM149 INV sub-population exhibited a persistent hyperinvasive phenotype. INV were hyper-glycolytic with increased glucose (2-NBDG) uptake; diminished glucose-6-phosphate (G6P) levels but elevated pyruvate and lactate, along with higher expression of phosphorylated-pyruvate dehydrogenase (pPDH) compared to WCC. Notably, inhibiting of glycolysis with lower doses of 2-DG (1 mM), non-cytotoxic to MDA-MB-231 and HCC1937, was effective in diminishing invasiveness of aggressive BC cell lines. In contrast, 3-Nitropropionic acid (3-NA), an inhibitor of succinate dehydrogenase, the enzyme that oxidizes succinate to fumarate in TCA cycle, and functions as complex II of ETC, had no significant effect on their invasiveness, although levels of TCA metabolites or detection of mitochondrial membrane potential with JC-1 staining, indicated that INV cells originally had functional TCA cycles and membrane potential. CONCLUSIONS: Hyper-glycolytic phenotype of invading cells caters to rapid energy production required for invasion while TCA cycle/ETC cater to cellular energy needs for sustenance in aggressive BC. Lower, non-cytotoxic doses of 2-DG can hamper invasion and can potentially be used as an adjuvant with other anti-cancer therapies without the usual side-effects associated with cytotoxic doses.

A Simple Assessment of the Eating and Swallowing Functions in Elderly Patients with Pneumonia.

It is important to assess the eating and swallowing functions of elderly people because they often develop aspiration pneumonia due to dysphagia. The most reliable modalities for assessing the eating and swallowing functions are videofluoroscopic examinations and videoendoscopic evaluations; however, these diagnostic modalities often cannot be performed in elderly people. Therefore, we established the Assessment of Swallowing Ability for Pneumonia (ASAP), which is an assessment of eating and swallowing functions in elderly patients with pneumonia that can be conducted by all health care professionals, and examined the usefulness thereof. The subjects included 130 patients with pneumonia (58 males, 72 females, average age: 82.2 ± 13.0) who had been admitted to the internal medicine department at our hospital between January 2016 and June 2016. The coefficient of correlation between ASAP and the Mann Assessment of Swallowing Ability (MASA) was 0.97, indicating a strong correlation, and the area under the curves (AUC) between the ASAP and the degrees of severity were 0.98, 0.95, and 0.94, respectively. We suggest that ASAP can be useful as a modality for assessing the eating and swallowing functions in elderly patients with pneumonia.

Predictors of Adverse Gastrointestinal Events After Stereotactic Body Radiation Therapy for Liver Tumors.

BACKGROUND/AIM: To identify predictors of adverse gastrointestinal (GI) events related to stereotactic body radiation therapy (SBRT) for liver tumors. PATIENTS AND METHODS: We retrospectively analyzed 56 patients who underwent SBRT for liver tumors at our institution between 2016 and 2021. The α/ß ratio of the GI tract (stomach, duodenum, and large intestine) was assumed to be 3 Gy in the Linear-Quadratic model (LQ model). The dose to the GI tract, that is, the biologically effective dose 3 (BED3) was converted to a 2 Gy equivalent dose (Gy2/3=2 Gy equivalent dose, α/ß=3). Using this 2 Gy equivalent dose, predictors of adverse GI events of Grade 2 or higher were investigated. RESULTS: The median observation period was 10 months (0-40 months) and median age was 77 years (range=29-93 years). Forty-three of the 56 patients had hepatocellular carcinoma and the other 13 had metastatic liver tumors. Tumors were irradiated with 30-54 Gy/5-18 fractions of planning target volume D95% prescription (80% isodose). Eight of the 56 patients had Grade 2 or higher adverse GI events. By univariate analysis, GI D1cc, Dmax, V20, V25, V30, and V35 were all significant predictors of Grade 2 or higher adverse GI events. Among these, gastrointestinal V35 was the most significant predictor of Grade 2 or higher adverse GI events. CONCLUSION: For SBRT of liver tumors, GI V35 was the best predictor of Grade 2 or higher adverse GI events.

A long-term survival case of bladder cancer with distant metastases: abscopal effect of brain metastases after stereotactic radiotherapy with immune checkpoint blockade therapy to lung metastases.

Brain metastases from bladder cancer are rare, with a poor prognosis. There is no standard treatment for bladder cancer with brain metastases; thus, palliative therapy is generally provided. We report a case of abscopal effect in a single brain metastasis from bladder cancer in a patient treated with focal stereotactic radiotherapy (total dose = 52 Gy, administered in eight fractions) with immune checkpoint blockade therapy for lung metastases, who achieved long-term disease-free survival (> 4 years). To our knowledge, although there have been some reports on abscopal effects in bladder cancer, there are no previous reports on patients with brain metastases. To date, the brain metastasis, which showed an "abscopal effect," continues to maintain complete regression.

Combining Carbon-Ion Irradiation and PARP Inhibitor, Olaparib Efficiently Kills BRCA1-Mutated Triple-Negative Breast Cancer Cells.

Background: Triple-negative breast cancer (TNBC) exhibits poor prognosis due to the lack of targets for hormonal or antibody-based therapies, thereby leading to limited success in the treatment of this cancer subtype. Poly (ADP-ribose) polymerase 1 (PARP1) is a critical factor for DNA repair, and using PARP inhibitor (PARPi) is one of the promising treatments for BRCA-mutated (BRCA mut) tumors where homologous recombination repair is impaired due to BRCA1 mutation. Carbon ion (C-ion) radiotherapy effectively induces DNA damages in cancer cells. Thus, the combination of C-ion radiation with PARPi would be an attractive treatment for BRCA mut TNBC, wherein DNA repair systems can be severely impaired on account of the BRCA mutation. Till date, the effectiveness of C-ion radiation with PARPi in BRCA mut TNBC cell killing remains unknown. Purpose: Triple-negative breast cancer cell lines carrying either wild type BRCA1, BRCA wt, (MDA-MB-231), or the BRCA1 mutation (HCC1937) were used, and the effectiveness of PARPi, olaparib, combined with C-ion beam or the conventional radiation, or X-ray, on TNBC cell killing were investigated. Methods: First, effective concentrations of olaparib for BRCA mut (HCC1937) cell killing were identified. Using these concentrations of olaparib, we then investigated their radio-sensitizing effects by examining the surviving fraction of MDA-MB-231 and HCC1937 upon X-ray or C-ion irradiation. In addition, the number of γH2AX (DSB marker) positive cells as well as their expression levels were determined by immunohistochemistry, and results were compared between X-ray irradiated or C-ion irradiated cells. Furthermore, PARP activities in these cells were also observed by performing immunohistochemistry staining for poly (ADP-ribose) polymer (marker for PARP activity), and their expression differences were determined. Results: Treatment of cells with 25 nM olaparib enhanced radio-sensitivity of X-ray irradiated HCC1937, whereas lower dose (5 nM) olaparib showed drastic effects on increasing radio-sensitivity of C-ion irradiated HCC1937. Similar effect was not observed in MDA-MB-231, not possessing the BRCA1 mutation. Results of immunohistochemistry showed that X-ray or C-ion irradiation induced similar number of γH2AX-positive HCC1937 cells, but these induction levels were higher in C-ion irradiated HCC1937 with increased PARP activity compared to that of X-ray irradiated HCC1937. Elevated induction of DSB in C-ion irradiated HCC937 may fully activate DSB repair pathways leading to downstream activation of PARP, subsequently enhancing the effectiveness of PARPi, olaparib, with lower doses of olaparib exerting noticeable effects in cell killing of C-ion irradiated HCC1937. Conclusions: From this study, we demonstrate that C-ion irradiation can exert significant DSB in BRCA mut TNBC, HCC1937, with high PARP activation. Thus, PARPi, olaparib, would be a promising candidate as a radio-sensitizer for BRCA mut TNBC treatment, especially for C-ion radiotherapy.

Abscopal complete regression of hepatocellular carcinoma with multiple pleural metastases.

Hepatocellular carcinoma (HCC) with extrahepatic metastasis is rare, and its prognosis is extremely poor. There is no standard treatment for HCC with extrahepatic metastasis. We report a case of abscopal effect in HCC with multiple pleural metastases in a patient who was treated with focal radiotherapy to extrahepatic metastasis, and achieved long-term survival. We performed radiotherapy only to the tumor in inferior vena cava and the proximal pleural tumor. The regimen comprised a total dose of 30 Gy administered in ten fractions to these tumors, followed by 12 Gy administered in four fractions (a total of 42 Gy in 14 fractions) as boost irradiation to the remaining tumor, and a complete regression was achieved. There have been some case reports on abscopal effects in HCC, but no reports on patients with multiple pleural metastases. To our knowledge, this is the first case report on the abscopal effect of focal radiotherapy resulting in complete regression of distant multiple pleural metastases.