Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation.

Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer.

Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adenocarcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telomerase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracellular adenosine triphosphate and high-mobility group box protein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpression augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade.

Subarachnoid Hemorrhage Related to a Ruptured Anterior Spinal Artery Aneurysm Associated with Bilateral Vertebral Artery Occlusion.

Objective: We report a rare case of a ruptured anterior spinal artery (ASA) aneurysm caused by bilateral vertebral artery (VA) occlusion. Case Presentations: A 78-year-old man suddenly developed severe headache and slight hemiparesis, and was admitted to our hospital. Computed tomography (CT) revealed subarachnoid hemorrhage, mainly in the posterior fossa. On emergency angiography, the right VA terminated at the origin of the posterior inferior cerebellar artery (PICA), and anastomoses between the PICA and the anterior inferior cerebellar artery (AICA) were observed, in addition to a saccular 3-mm aneurysm with bleb originating from the PICA-AICA anastomosis. Left vertebral arteriography demonstrated that the left VA was occluded segmentally at the V4 level and revealed a tortuous arterial network filling the distal VA. Based on the location of the bleeding, the right VA aneurysm was considered to have ruptured. After balloon test occlusion of the right VA, parent artery occlusion was performed without complications. The patient had no neurological changes immediately after surgery, but several hours later, he stopped breathing. Retrospective analysis revealed an ASA aneurysm, which was determined to be the bleeding source. Although conservative treatment was performed, he died the fourth day after onset without neurological improvement. Conclusion: In cases of subarachnoid hemorrhage associated with bilateral VA occlusion, an aneurysm formed by hemodynamic stress may be the source of hemorrhage. It is important to suspect aneurysms in the extracranial collaterals, such as the ASA, and intracranial collaterals such as the PICA-AICA anastomosis.

[A Case of Gastric Small Cell Carcinoma with Rapid Regrowth after Surgery].

The patient was a 59-year-old man with type 2 advanced gastric cancer in the antrum. Abdominal computed tomography revealed the primary tumor with regional lymph node metastasis. Distal gastrectomy and D2 lymph node dissection were performed. Histopathological findings indicated gastric small cell carcinoma. Lymph node metastasis was observed microscopically in the #6 lymph nodes. Peritoneal lavage cytology was positive. The pathologic stage of the disease was pT2(MP), med, INF b, ly2, v2, pPM0, pDM0, pN2(6/33: #5, #6), M1, P0, CY1, H0, stage Ⅳ, R1(cy+). After surgery, he received chemotherapy with capecitabine plus oxaliplatin. However, after 1 course of therapy the disease had progressed, and the patient was diagnosed with peritoneal metastasis. Chemotherapy of CDDP plus CPT-11 was initiated, and after 5 courses the patient died.

Perfusion Computed Tomography Parameters Are Useful for Differentiating Glioblastoma, Lymphoma, and Metastasis.

BACKGROUND: Perfusion computed tomography (PCT) reflects blood flow and capillary condition, which is valuable in assessing brain tumors. We evaluated PCT parameters at the tumor (t) and peritumoral (p) region to differentiate malignant brain tumors. METHODS: We performed PCT in 39 patients with supratentorial malignant brain tumors (22 glioblastomas, 6 lymphomas, 11 metastases). Regions of interests were placed manually at tumor, peritumoral region, and contralateral normal-appearing white matter. Cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability surface (PS) were measured. These parameters were divided by those of contralateral normal-appearing white matter to normalize at tumor (relative [r]CBVt, rCBFt, rMTTt, rPSt) and peritumoral regions (rCBVp, rCBFp, rMTTp, rPSp). The parameters were evaluated with Mann-Whitney U test and receiver operating characteristics analyses. Stepwise analyses also were performed to select useful PCT parameters for differentiating these tumors. RESULTS: The rCBFt and rCBVt of glioblastoma (GBM) were greater than those of primary central nervous system lymphoma (PCNSL) (P = 0.0005, 0.0002) and brain metastasis (METS) (P = 0.0044, 0.0028). The rMTTp of METS was greater than that of GBM and PCNSL (P = 0.0001, 0.0007). The combination of rCBVt and rPSt could differentiate GBM from other tumors with sensitivity and specificity of 81.8% and 94.1%. The combination of rCBFp and rMTTp could differentiate METS from other tumors with sensitivity and specificity of 90.9% and 82.1%. CONCLUSIONS: Our study introduces and supports the usefulness of PCT parameters for differentiation among GBM, PCNSL, and METS. rCBVt and rPSt may be the best predictors of GBM. rCBFp and rMTTp may be the best predictors of METS.

[A Case of Long-Term Disease-Free Survival of a Gastric Cancer Patient with Peritoneal Dissemination and Transverse Colon Invasion].

A 71-year-old man visited our hospital because ofepigastralgia and anorexia. Upper gastrointestinal endoscopy revealed type 1 gastric cancer. Contrast-enhanced abdominal CT revealed gastric wall thickening in the midgastric region and direct invasion ofthe transverse colon. CT findings also revealed a suspicion ofdissemination on the omentum and para-aortic lymph node swelling. We diagnosed gastric cancer with transverse colon invasion. Therefore, we performed distal gastrectomy with transverse colectomy and D2+No.16b1 lymph node dissection after obtaining patient consent. We observed direct tumor invasion into the transverse colon and seeding nodules on the omentum. Liver metastasis was not seen, and ascitic cytology was negative. He was discharged 16 days postoperatively, without any complications. Histopathological analysis revealed poorly differentiated adenocarcinoma and gastrocolic fistula. Postoperatively, S-1 was administered for 4 years as adjuvant chemotherapy. There has been no recurrence for 9 years after surgery.

[A Case of Intussusception Caused by Colon Cancer in A 25-Year-Old Woman].

A 25-year-old woman presented to our hospital with left flank pain and diarrhea. Contrast-enhanced abdominal computed tomography(CT)showed a target sign in the descending colon. She was diagnosed with intussusception of the colon. Colonoscopy revealed a tumor at the splenic flexure. We performed surgery and found an invaginated transverse colon at the splenic flexure. Reduction was unsuccessful with Hutchinson's maneuver, and we performed partial resection of the invaginated colon. Histopathological diagnosis was adenocarcinoma, tub1, SM2. Adult intussusception is uncommon, especially in young adults. It is usually caused by a polyp or tumor. We report a case of intussusception caused by colon cancer in a young female patient, and review the literature.

[A Case of Long-Term Survival with Multidisciplinary Therapy for a Patient with Multiple Metastases from Rectal Cancer].

Combined modality therapy is sufficient to treat advanced rectal cancer with multiple metastases. Her, we report a case of long-term survival in a patient with multiple metastases from rectal cancer. A5 8-year-old man had previously undergone low anterior resection for advanced rectal cancer. Multiple liver and lung metastases were identified prior to operation; therefore, we initiated chemotherapy(FOLFOX). Partial resection of metastatic lesions and radiofrequency ablation(RFA)were also administered, but newly developed liver, lung, and adrenal gland metastases were identified. We changed the chemotherapy regimen and administered topical therapies(partial resection, RFA, hepatic arterial infusion chemotherapy, radiotherapy)for each chemotherapy-refractory metastatic lesion. Although the patient is in a tumor-bearing state, he is still alive 10 years after his first operation. This combined modality therapy is an option for patients with chemotherapy-refractory metastases from rectal cancer.

[A Case of Goblet Cell Carcinoid of the Appendix Treated by Laparoscopic Ileocecal Resection after Diagnosis by Colonoscopic Examination for Positive Occult Blood].

A79 -year-old woman underwent colonoscopic examination for positive occult blood. Aneoplastic lesion was seen in the orifice of the vermiform appendix. She was referred to our hospital and underwent colonoscopic examination again. The biopsy revealed poorly differentiated adenocarcinoma or mixed adenoneuroendocrine carcinoma(MANEC), and she was diagnosed with carcinoma of the appendix. She was treated by laparoscopic ileocecal resection with lymph node dissection (D3). Histopathological examination revealed goblet cell carcinoid(GCC)of the appendix with serosal invasion. No metastasis was detected in the dissected lymph nodes. This patient has been followed-up for 6 months after surgery and no recurrences have been detected.

Preoperative histological grading of meningiomas using apparent diffusion coefficient at 3T MRI.

PURPOSE: We assessed whether a high b-value DWI at b=4000s/mm(2) would discriminate the histopathological differentiation of the tumor grade of meningiomas, and also focused on the relationship between radiologic features and the tumor grade. MATERIALS AND METHODS: We acquired DWI at 3T with b=1000 and b=4000s/mm(2) in 77 patients (42, 31 and 4 patients were WHO grades I (G1), II (G2), and III (G3), respectively). The apparent diffusion coefficient (ADC) was measured by placing multiple regions of interest (ROIs) on ADC maps. The ADC values of each tumor were determined preoperatively from several ROIs, and expressed as the minimum (ADCMIN), mean (ADCMEAN), and maximum absolute values (ADCMAX). We evaluated the relationship between ADCs and histological findings, and assessed the radiologic features such as tumor location, tumor size, presence/absence of peritumoral edema, shape of the tumor, presence/absence of bone destruction or hyperplasia, status of contrast enhancement, presence/absence of calcification and cyst. RESULTS: ADCs of the meningiomas were inversely correlated with the histological grade of meningiomas. According to results of the discriminant analysis, the apparent log likelihood value was greatest for ADCMIN at b=4000. Furthermore, only the ADCMIN value at b=4000 was significantly correlated with the histological grade of meningiomas when we performed a multiple logistic regression analysis to identify the significant independent factors such as shape of tumor, presence/absence of bone destruction, status of contrast enhancement, presence/absence of cyst and ADCMIN at b=4000. CONCLUSION: A meningioma with a low ADCMIN at a high b-value might imply a high-grade meningioma.

[Efficacy of chemotherapy combined with bevacizumab for unresectable advanced or recurrent colorectal cancer].

Systemic treatment for metastatic or advanced colorectal cancer(mCRC)has remarkably progressed during recent years. All previously untreated mCRC patients at our institution between November, 2007 and June, 2010 were retrospectively evaluated. Of 72 patients, 39 were treated with chemotherapy alone, and 33 were treated with chemotherapy plus bevacizumab(BV). The median progression-free survival(mPFS)was 329 days in the group given chemotherapy plus BV, compared with 209 days in the group given chemotherapy alone(p=0. 0189). In sub-group analysis of those treated with chemotherapy plus BV, mPFS between 70 y/o

Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment.

BACKGROUND: The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. MATERIALS AND METHODS: Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6-65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan-Meier survival curves (log-rank test). RESULTS: It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. DISCUSSION AND CONCLUSION: High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab.

Lymphomas and glioblastomas: differences in the apparent diffusion coefficient evaluated with high b-value diffusion-weighted magnetic resonance imaging at 3T.

BACKGROUND AND PURPOSE: As the usefulness of the apparent diffusion coefficient (ADC) obtained from diffusion-weighted images (DWI) for the differential diagnosis between glioblastoma and primary central nervous system lymphoma is controversial, we assessed whether high b-value DWI at b 4000 s/mm(2) could discriminate between glioblastoma and lymphoma. We also compared the power of high- and standard b-value (b-4000, b-1000) imaging on a 3-Tesla (3T) magnetic resonance (MR) instrument. MATERIALS AND METHODS: This study was approved by our Institutional Review Board. We acquired DWI at 3T with b = 1000 and b = 4000 s/mm(2) in 10 patients with lymphoma and 14 patients with glioblastoma. The ADC was measured by placing multiple regions of interest (ROI) on ADC maps of the site of enhanced lesions on contrast-enhanced T1-weighted MR images. We avoided hemorrhagic and cystic lesions by using T1-, T2-, FLAIR-, and T2* MR images. The ADC values of each tumor were determined preoperatively from several ROI and expressed as the minimum-, mean-, and maximum ADC value (ADC(MIN), ADC(MEAN), ADC(MAX)). We evaluated the relationship between ADCs and histological information including tumor cellularity. RESULTS: All ADC values were statistically associated with tumor cellularity. ADC(MIN) at b-4000 was associated with tumor cellularity more significantly than ADC(MIN) at b-1000. All ADC values were lower for lymphoma than glioblastoma and the statistical difference was larger at b = 4000- than b = 1000 s/mm(2). According to the results of discriminant analysis, the log likelihood was greatest for ADC(MIN) at b = 4000. At a cut-off value of ADC(MIN) = 0.500 × 10(-3)mm(2)/s at b-4000 it was possible to differentiate between lymphoma and glioblastoma (sensitivity 90.9%, specificity 91.7%). CONCLUSIONS: Calculating the ADC value is useful for distinguishing lymphoma from glioblastoma. The lowest degree of overlapping and a better inverse correspondence with tumor cellularity were obtained with ADC(MIN) at b-4000 s/mm(2) at 3T MRI.

Role of perfusion-weighted imaging at 3T in the histopathological differentiation between astrocytic and oligodendroglial tumors.

OBJECTIVE: The differentiation of oligodendroglial tumors from astrocytic tumors is important clinically, because oligodendroglial tumors are more chemosensitive than astrocytic tumors. This study was designed to clarify the usefulness of 3T MR perfusion imaging (PWI) in the histopathological differentiation between astrocytic and oligodendroglial tumors. This is because there is a growing interest in the diagnostic performance of 3T MR imaging, which has the advantages of a higher signal-to-noise ratio (SNR) and greater spatial and temporal resolution. MATERIALS AND METHODS: This study retrospectively included 24 consecutive patients with supratentorial, WHO grade II and III astrocytic and oligodendroglial tumors (7 astrocytic, 10 oligoastrocytic, and 7 oligodendroglial tumors) that were newly diagnosed and resected between November 2006 and December 2009 at Hiroshima University Hospital. These patients underwent dynamic susceptibility contrast-enhanced (DSC) PWI relative cerebral blood volume (rCBV) measurements before treatment. Astrocytic tumors were designated as the astrocytic group, and oligoastrocytic and oligodendroglial tumors as the oligodendroglial group. The regions of interest with the maximum rCBV values within the tumors were normalized relative to the contra-lateral white matter (rCBVmax). RESULTS: The average rCBVmax of astrocytic tumors (2.01±0.68) was significantly lower than that of the oligoastrocytic (4.60±1.05) and oligodendroglial tumors (6.17±0.867) (P<0.0001). A cut-off value of 3.0 allowed to differentiate the oligodendroglial group from the astrocytic group at 100% sensitivity and 87.5% specificity. CONCLUSION: The rCBVmax values obtained from 3T MR PWI may be useful as an adjunct to the postoperative histopathological diagnosis of glioma patients.

Magnetic resonance spectroscopic detection of lactate is predictive of a poor prognosis in patients with diffuse intrinsic pontine glioma.

Diffuse brainstem glioma has a poor prognosis, and there are few long-term survivors. We looked for clinical, conventional magnetic resonance (MR), and MR spectroscopic (MRS) findings predictive of the prognosis of patients with brainstem glioma. Our institutional review board approved this retrospective study of 23 patients with diffuse intrinsic pontine or diffuse medullary brainstem glioma treated during the period 2000-2009. To evaluate prognostic values, we performed a Kaplan-Meier survival analysis (log-rank test) that incorporated the patients' age and sex, symptom duration, the presence or absence of cranial nerve palsy, long tract sign, ataxia, and cysts, the chemotherapeutic regimen, Gd enhancement, longitudinal and cerebellar extension, basilar artery encasement, and MRS parameters. Of the 23 diffuse brainstem gliomas, 19 were located at the pons (ratio of male to female patients, 1.1:1). The mean age of the 23 patients was 15.9 years (range, 4-50 years); 16 were aged <20 years. The duration of overall survival was 19.7 months; in patients with diffuse intrinsic pontine glioma, it was 16.6 months, and in patients aged <20 years, it was 11.8 months. Clinical and conventional MR findings at presentation were not predictive of the prognosis in children with diffuse intrinsic pontine glioma. In addition, a patient age <20 years and the detection of lactate by MRS were poor prognostic factors. The MRS detection of lactate is a prognostic factor in patients with diffuse intrinsic pontine glioma. Additional studies of larger patient populations using other imaging modalities are needed.

Cerebral angiography using gadolinium as an alternative contrast medium in a patient with severe allergy to iodinated contrast medium.

We report cerebral digital subtraction angiography (DSA) using Gadolinium in a patient allergic to iodinated contrast media. A 77-year-old woman was admitted to our hospital for surgical resection of a brain tumor. Although a DSA was requested as a preoperative examination, the patient had a history of allergic reaction to non-ionic iodinated contrast medium. Therefore, DSA was performed using Gadolinium. The DSA showed no tumor stain and normal venous drainage. The patient underwent surgical resection of the tumor and was discharged with no new neurological deficit. DSA using Gadolinium was useful in a patient with an anaphylactic reaction to iodinated contrast media.

Expression of phosphoprotein enriched in astrocytes 15 kDa (PEA-15) in astrocytic tumors: a novel approach of correlating malignancy grade and prognosis.

Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional protein that was first identified in brain astrocytes and that has subsequently been shown to be expressed in different tissues. Despite its many important roles, the clinical significance of PEA-15 expression levels in astrocytic tumors has yet to be properly defined. We studied the PEA-15 expression pattern of 65 patients [diagnosed according to World Health Organization (WHO) criteria] with diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV). PEA-15 expression levels were immunohistochemically measured and categorized as no, low, or high expression. All tumors expressed PEA-15 in our study. Twenty-three (35.4%) and 42 (64.6%) tumors expressed low and high PEA-15 levels, respectively. In grade II astrocytoma (diffuse astrocytoma) and grade III astrocytoma (anaplastic astrocytoma), 100% and 88.9% of patients expressed high PEA-15 levels, respectively, while a smaller number (50%) of patients with grade IV astrocytoma (glioblastoma) expressed high PEA-15 levels. PEA-15 expression level was inversely associated with WHO grade (P = 0.0006). Next, we evaluated prognosis and PEA-15 expression levels in 43 patients with high-grade astrocytomas based on the following parameters: age, gender, WHO grade, surgical resection extent, MIB-1 labeling index (LI), and PEA-15 expression level. Multivariable analyses revealed that high PEA-15 expression level displayed a significant correlation with longer overall survival (OS) in high-grade astrocytomas (P = 0.0024). Patients with total resection survived significantly longer (P = 0.0044) than those with lower resection extent, while patients with MIB-1 labeling index ≤25% indicated significant (P = 0.0434) correlation with OS as well. In conclusion, PEA-15 expression level was inversely associated with WHO grade and may serve as an important prognostic factor for high-grade astrocytomas.

Glioblastoma treated with postoperative radio-chemotherapy: prognostic value of apparent diffusion coefficient at MR imaging.

PURPOSE: To retrospectively evaluate whether the mean, minimum, and maximum apparent diffusion coefficient (ADC) of glioblastomas obtained from pretreatment MR images is of prognostic value in patients with glioblastoma. MATERIALS AND METHODS: The institutional review board approved our study and waived the requirement for informed patient consent. Between February 1998 and January 2006, 33 patients (24 males, 9 females; age range 10-76 years) with supratentorial glioblastoma underwent pretreatment magnetic resonance (MR) imaging. The values of the mean, minimum, and maximum ADC (ADC(mean), ADC(MIN), and ADC(MAX), respectively) of each tumor were preoperatively determined from several regions of interest defined in the tumors. After surgical intervention, all patients underwent irradiation and chemotherapy performed according to our hospital protocol. The patient age, symptom duration, Karnofsky performance scale score, extent of surgery, and ADC were assessed using factor analysis of overall survival. Prognostic factors were evaluated using Kaplan-Meier survival curves, the log-rank test, and multiple regression analysis with the Cox proportional hazards model. RESULTS: Likelihood ratio tests confirmed that ADC(MIN) was the strongest among the three prognostic factors. Total surgical removal was the most important predictive factor for overall survival (P<0.01). ADC(MIN) was also statistically correlated with overall survival (P<0.05) and could be used to classify patients into different prognostic groups. Interestingly, ADC(MIN) was also the strongest prognostic factor (P<0.01) in the group of patients in whom total tumor removal was not possible. CONCLUSION: The ADC(MIN) value obtained from pretreatment MR images is a useful clinical prognostic biomarker in patients with glioblastoma.