Who should receive single-fraction palliative radiotherapy for gastric cancer bleeding?: An exploratory analysis of a multicenter prospective observational study (JROSG 17-3).

Purpose: Although the Palliative Prognostic Index (PPI) has been used to predict survival in various cancers, to our knowledge, no study has examined its applicability in gastric cancer. This study aimed to determine the baseline PPI cutoff value for recommending single-fraction radiotherapy in patients with bleeding gastric cancer. Materials and methods: This was a secondary analysis of the Japanese Radiation Oncology Study Group (JROSG) 17-3, a multicenter prospective study of palliative radiotherapy for bleeding gastric cancer. Discrimination was evaluated using a time-dependent receiver operating characteristic curve, and the optimal cutoff value was determined using the Youden index. A calibration plot was used to assess the agreement between predicted and observed survival. Results: We enrolled 55 patients in JROSG 17-3. The respective median survival times were 6.7, 2.8, and 1.0 months (p = 0.021) for patients with baseline PPI scores of ≤ 2, 2 < PPI ≤ 4, and PPI > 4. The areas under the curve for predicting death within 2, 3, 4, and 5 months were 0.813, 0.787, 0.775, and 0.721, respectively. The negative predictive value was highest when survival < 2 months was predicted and the Youden index was highest when the cutoff PPI value was 2. The calibration curve showed a reasonable agreement between the predicted and observed survival. Conclusion: Baseline PPI is useful for estimating short-term prognosis in patients treated with palliative radiotherapy for gastric cancer bleeding. A cutoff PPI value of 2 for estimating survival ≤ 2 months should be used to recommend single-fraction radiotherapy.

Treatment response after palliative radiotherapy for bleeding gastric cancer: a multicenter prospective observational study (JROSG 17-3).

BACKGROUND: Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. METHODS: Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) bleeding response rate at 4 weeks. Response entailed all of the following criteria: (i) hemoglobin levels ≥ 8.0 g/dL; (ii) 7 consecutive days without blood transfusion anytime between enrollment and blood sampling; and (iii) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or re-irradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. RESULTS: We enrolled 55 patients from 15 institutions. The ITT response rates were 47%, 53%, and 49% at 2, 4, and 8 weeks, respectively. The per-protocol response rates were 56%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Neither response nor BED (α/ß = 10) predicted overall survival. Multivariable Fine-Gray model showed that BED was not a significant predictor of response. Univariable Cox model showed that BED was not significantly associated with re-bleeding. Grades 1, 2, 3, and, ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSIONS: The per-protocol response rate increased to 90% during the 8-week follow-up. The frequent occurrence of death starting shortly after enrollment lowered the ITT response rate. BED was not associated with survival, bleeding response, or re-bleeding.

Traffic of infused bone marrow cells after genetically-labeled syngeneic bone marrow transplantation following lethal irradiation in mice.

UNLABELLED: Bone marrow (BM) cells are considered the source of stem cells for various organs. However, how quickly BM cells can penetrate and constitute lymphoid organs remains elusive. In the present study, we addressed this issue in a model using genetically-labeled syngeneic BM transplantation (BMT). METHODS: Donor BM cells were obtained from "green mice", transgenic mice with enhanced GFP. Lethally irradiated C57BL/6 mice were infused with 1 x 10(6) BM cells from the green mice through the tail vein. BM chimerism was analyzed by FACS and the presence of donor BM cells in thoracoabdominal organs was assessed by fluorescence microscopy. The commitment of BM cells was examined by immunohistochemical staining using epithelium-, macrophage-, B and T-lymphocyte, and endothelium-specific antibodies. RESULTS: BM chimerism reached 40+/- 18.5%, 82.6 +/- 23.4%, and 72 +/- 18% (mean +/- SD) at 1, 4, and 12 wks after BMT, respectively. GFP-positive cells were detected in all organs in the course of chimeric formation. Most GFP-positive cells were T and B lymphocytes in lymphoid systems including spleen, thymus, mesenteric lymph nodes and microvilli, and some were positive for macrophage and endothelial cell markers. CONCLUSIONS: Our results indicate that BM-derived cells migrate rapidly into various thoracoabdominal organs after BMT, and that lymphoid tissues are predominantly replaced with infused BM in lethally-irradiated mice. This confirmed the previous finding by others and suggests high interest of this model for further studies to characterize kinetics and roles of infused cells.

Participation of bone marrow cells in biliary fibrosis after bile duct ligation.

BACKGROUND AND AIM: Bone marrow derived cells are involved in the process of hepatic fibrosis secondary to chronic injury. However, it is not yet known how quickly this event occurs in acute fibrosis models. The purpose of this study was to determine the role of bone marrow cells in rapid fibrosis following bile duct ligation in mice using green fluorescent protein (GFP) expressing bone marrow cells. METHOD: After whole body irradiation, 1 x 10(6) donor whole bone marrow cells from green fluorescent protein(+/-) mice were transplanted into C57BL/6 recipients via the tail vein. Four weeks after bone marrow transplantation, chimeric mice were subjected to common bile duct ligation, and livers of these animals were histologically examined after bile duct ligation using anti-fibroblast specific protein (FSP)-1 antibody and anti-alpha-smooth muscle actin (alpha-SMA) antibody. RESULTS: Periductal fibrosis consisting of fibroblast specific protein-positive cells was demonstrated histologically as early as day 7. Most of the fibrotic cells were green fluorescent protein-negative, however, a significant number of cells were green fluorescent protein-positive and some were also anti-FSP or alpha-SMA-positive. CONCLUSION: Differentiation of bone marrow derived cells into activated fibroblast and myofibroblast-like phenotypes occurs in the very early course of periductal fibrosis following bile duct ligation, suggesting a new strategy for prevention of biliary fibrosis by inhibiting migration of bone marrow cells to liver.