Prognostic factors in hepatocellular carcinoma patients with bone metastases.

PURPOSE: To identify the prognostic factors that could influence survival and to compare prognoses of the patients with the number of the risk factors that might assist in the adequate management of hepatocellular carcinoma (HCC) patients with bone metastases that showed a heterogeneous range of survival. MATERIALS AND METHODS: A total of 41 patients, treated with radiotherapy (RT) for bone metastases from HCC from 2014 to 2017, were enrolled retrospectively. Survival was determined by the Kaplan-Meier method from the start of the RT for metastatic bone lesions. Pre-RT clinical features were evaluated and their influences on survival were analyzed. The significant factors were considered to compare survivals according to the number of prognostic factors. RESULTS: Median follow-up was 6.0 months (range, 0.5 to 47.0 months). The median overall survival was 6.5 months, and the 1-year and 2-year survival rates were 35.5% and 13.5%, respectively. Multivariate analysis revealed that the Child-Pugh class A group, alpha-fetoprotein increased more than 30 ng/mL, and HCC size of more than 5 cm were associated with worse overall survival. The median survivals in HCC with none, 1, 2, and 3 of the aforementioned risk factors were 19.5, 9.0, 2.5, and 1.0 months, respectively (p < 0.05). CONCLUSION: Our results show that the overall survivals were significantly different according to the number of the risk factors among HCC patients with bone metastases who showed various lengths of survival.

Maximum diameter versus volumetric assessment for the response evaluation of vestibular schwannomas receiving stereotactic radiotherapy.

PURPOSE: To explore the feasibility of maximum diameter as a response assessment method for vestibular schwannomas (VS) after stereotactic radiosurgery or fractionated stereotactic radiotherapy (RT), we analyzed the concordance of RT responses between maximum diameters and volumetric measurements. Materials and. METHODS: Forty-two patients receiving curative stereotactic radiosurgery or fractionated stereotactic RT for VS were analyzed retrospectively. Twelve patients were excluded: 4 did not receive follow-up magnetic resonance imaging (MRI) scans and 8 had initial MRI scans with a slice thickness >3 mm. The maximum diameter, tumor volume (TV), and enhanced tumor volume (ETV) were measured in each MRI study. The percent change after RT was evaluated according to the measurement methods and their concordances were calculated with the Pearson correlation. The response classifications were determined by the assessment modalities, and their agreement was analyzed with Cohen kappa statistics. RESULTS: Median follow-up was 31.0 months (range, 3.5 to 86.5 months), and 90 follow-up MRI studies were analyzed. The percent change of maximum diameter correlated strongly with TV and ETV (r(p) = 0.85, 0.63, p = 0.000, respectively). Concordance of responses between the Response Evaluation Criteria in Solid Tumors (RECIST) using the maximum diameters and either TV or ETV were moderate (kappa = 0.58; 95% confidence interval, 0.32-0.85) or fair (kappa = 0.32; 95% confidence interval, 0.05-0.59), respectively. Conclusions: The percent changes in maximum diameter and the responses in RECIST were significantly concordant with those in the volumetric measurements. Therefore, the maximum diameters can be used for the response evaluation of VS following stereotactic RT.

Effect of rectal enema on intrafraction prostate movement during image-guided radiotherapy.

INTRODUCTION: Rectal volume and movement are major factors that influence prostate location. The aim of this study was to assess the effect of a rectal enema on intrafraction prostate motion. METHODS: The data from 12 patients with localised prostate cancer were analysed. Each patient underwent image-guided radiotherapy (RT), receiving a total dose of 70 Gy in 28 fractions. Rectal enemas were administered to all of the patients before each RT fraction. The location of the prostate was determined by implanting three fiducial markers under the guidance of transrectal ultrasound. Each patient underwent preparation for IGRT twice before an RT fraction and in the middle of the fraction. The intrafraction displacement of the prostate was calculated by comparing fiducial marker locations before and in the middle of an RT fraction. RESULTS: The rectal enemas were well tolerated by patients. The mean intrafraction prostate movement in 336 RT fractions was 1.11 ± 0.77 mm (range 0.08-7.20 mm). Intrafraction motions of 1, 2 and 3 mm were observed in 56.0%, 89.0% and 97.6% of all RT fractions, respectively. The intrafraction movements on supero-inferior and anteroposterior axes were larger than on the right-to-left axes (P < 0.05). The CTV-to-PTV margin necessary to allow for movement, calculated using the van Herk formula (2.5Σ + 0.7σ), was 1.50 mm. CONCLUSIONS: A daily rectal enema before each RT fraction was tolerable and yielded little intrafraction prostate displacement. We think the use of rectal enemas is a feasible method to reduce prostate movement during RT.

Interfraction prostate movement in bone alignment after rectal enema for radiotherapy.

PURPOSE: To assess the effect of a rectal enema on interfraction prostate movement in bone alignment (BA) for prostate radiotherapy (RT), we analyzed the spatial difference in prostates in a bone-matched setup. MATERIALS AND METHODS: We performed BA retrospectively with data from prostate cancer patients who underwent image-guided RT (IGRT). The prostate was identified with implanted fiducial markers. The setup for the IGRT was conducted with the matching of three fiducial markers on RT planning computed tomography images and those on two oblique kV x-ray images. Offline BA was performed at the same position. The coordinates of a virtual prostate in BA and a real prostate were obtained by use of the ExaxTrac/NovalisBody system, and the distance between them was calculated as the spatial difference. Interfraction prostate displacement was drawn from the comparison of the spatial differences. RESULTS: A total of 15 patients with localized prostate cancer treated with curative hypofractionated IGRT were enrolled. A total of 420 fractions were analyzed. The mean of the interfraction prostate displacements after BA was 3.12±2.00 mm (range, 0.20-10.53 mm). The directional difference was profound in the anterior-posterior and supero-inferior directions (2.14±1.73 mm and 1.97±1.44 mm, respectively) compared with the right-left direction (0.26±0.22 mm, p<0.05). The required margin around the clinical target volume was 4.97 mm with the formula of van Herk et al. CONCLUSIONS: The interfraction prostate displacement was less frequent when a rectal enema was performed before the procedure. A rectal enema can be used to reduce interfraction prostate displacement and resulting clinical target volume-to-planning target volume margin.

DNA ligase4 as a prognostic marker in nasopharyngeal cancer patients treated with radiotherapy.

BACKGROUND: The capability for DNA double-strand breaks (DSBs) repair is crucial for inherent radiosensitivity of tumor and normal cells. We have investigated the clinicopathologic significance of DNA repair gene expression in nasopharyngeal (NP) carcinoma. MATERIALS AND METHODS: A total of 65 NP cancer patients who received radiotherapy were included. The immunopositivity to Ku 70, DNA-PKcs, MRN, RAD50, XRCC4, and LIG4 were examined in all tumor tissues. RESULTS: The patients comprised 42 males and 23 females, with a median age of 56 years (range, 18-84). The expression levels of RAD50 (0,+1,+2,+3) were 27.7%, 32.3%, 21.5%, and 18.5%. LIG4 (±) were 43.1% and 56.9% respectively. The 5-year OS rate of patients with LIG4 (±) were 90% and 67.9%, respectively (p=0.035). The 5-year TTP rate of patients with LIG4 (±) were 75.9%, 55.5%, respectively (P=0.039). CONCLUSIONS: Our results suggest the possibility of predicting the radiosensitivity of NP cancer by performing immunohistochemical analysis of LIG4.

Epidermal growth factor receptor is related to poor survival in glioblastomas: single-institution experience.

PURPOSE: There are conflicting results surrounding the prognostic significance of epidermal growth factor receptor (EGFR) status in glioblastoma (GBM) patients. Accordingly, we attempted to assess the influence of EGFR expression on the survival of GBM patients receiving postoperative radiotherapy. MATERIALS AND METHODS: Thirty three GBM patients who had received surgery and postoperative radiotherapy at our institute, between March 1997 and February 2006, were included. The evaluation of EGFR expression with immunohistochemistry was available for 30 patients. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. RESULTS: EGFR was expressed in 23 patients (76.7%), and not expressed in seven (23.3%). Survival in EGFR expressing GBM patients was significantly less than that in non-expressing patients (median survival: 12.5 versus 17.5 months, p=0.013). Patients who received more than 60 Gy showed improved survival over those who received up to 60 Gy (median survival: 17.0 versus 9.0 months, p=0.000). Negative EGFR expression and a higher radiation dose were significantly correlated with improved survival on multivariate analysis. Survival rates showed no differences according to age, sex, and surgical extent. CONCLUSION: The expression of EGFR demonstrated a significantly deleterious effect on the survival of GBM patients. Therefore, approaches targeting EGFR should be considered in potential treatment methods for GBM patients, in addition to current management strategies.

Treatment outcomes between concurrent chemoradiotherapy and combination of surgery, radiotherapy, and/or chemotherapy in stage III and IV maxillary sinus cancer: multi-institutional retrospective analysis.

PURPOSE: The incidence of maxillary sinus cancer (MSC) is extremely rare, representing less than 1% of all cancers. Because of its rarity, the management of locally advanced MSC is a challenging issue. The objective of the present study was to retrospectively compare the efficacy of 2 traditional treatment strategies, concurrent chemoradiotherapy (CCRT) versus combination of surgery and radiotherapy and/or chemotherapy (SRCT) in MSC. PATIENTS AND METHODS: From 1989 to 2010, 65 patients with histologically confirmed stage III or IVA/IVB were retrospectively analyzed. RESULTS: The median age of our subjects was 60 years (range 36 to 81). The present study involved 18 women (27.7%) and 47 men (72.3%). Of the 65 patients, 52 (80.0%) had squamous cell carcinoma. The TNM stage was stage III, as determined by the American Joint Committee on Cancer, 6th edition, in 27 patients (41.5%). Stage IVA or IVB was observed in 38 patients (58.5%). Of the 65 patients, 41 underwent treatment. Of these 41 patients, 26 and 15 patients underwent SRCT and CCRT, respectively. During the 75.6 months (range 6.4 to 249.4) of median follow-up, the median progression-free survival duration was 45.1 months (95% confidence interval 0.0 to 142.7). The 5-year overall survival rate was 64.8%. However, the patients who had undergone surgery had better progression-free survival (hazard ratio 2.363, 95% confidence interval 1.098 to 5.085, P = .028) and overall survival (hazard ratio 4.989, 95% confidence interval 1.646 to 15.118, P = .004). The SRCT group had a better progression-free survival (P = .043) and overall survival (P = .029) duration than did the CCRT group. CONCLUSION: SRCT might be superior to CCRT for locally advanced MSC. Additional studies comparing the treatment outcomes of CCRT with SRCT are warranted.

Interleukin-24 is correlated with differentiation and lymph node numbers in rectal cancer.

AIM: To assess the significance of interleukin (IL)-24 and vascular endothelial growth factor (VEGF) expression in lymph-node-positive rectal cancer. METHODS: Between 1998 and 2005, 90 rectal adenocarcinoma patients with lymph node involvement were enrolled. All patients received radical surgery and postoperative pelvic chemoradiotherapy of 50.4-54.0 Gy. Chemotherapy of 5-fluorouracil and leucovorin or levamisole was given intravenously during the first and last week of radiotherapy, and then monthly for about 6 mo. Expression of IL-24 and VEGF was evaluated by immunohistochemical staining of surgical specimens, and their relations with patient characteristics and survival were analyzed. The median follow-up of surviving patients was 73 mo (range: 52-122 mo). RESULTS: IL-24 expression was found in 81 out of 90 patients; 31 showed weak intensity and 50 showed strong intensity. VEGF expression was found in 64 out of 90 patients. Negative and weak intensities of IL-24 expression were classified as negative expression for analysis. IL-24 expression was significantly reduced in poorly differentiated tumors in comparison with well or moderately differentiated tumors (P = 0.004), N2b to earlier N stages (P = 0.016), and stage IIIc to stage IIIa or IIIb (P = 0.028). The number of involved lymph nodes was also significantly reduced in IL-24-positive patients in comparison with IL-24-negative ones.There was no correlation between VEGF expression and patient characteristics. Expression of IL-24 and VEGF was not correlated with survival, but N stage and stages were significantly correlated with survival. CONCLUSION: IL-24 expression was significantly correlated with histological differentiation, and inversely correlated with the degree of lymph node involvement in stage III rectal cancer.

Influence of intravenous contrast agent on dose calculations of intensity modulated radiation therapy plans for head and neck cancer.

BACKGROUND AND PURPOSE: To evaluate the effect of an intravenous contrast agent (CA) on dose calculations and its clinical significance in intensity modulated radiation therapy (IMRT) plans for head and neck cancer. MATERIALS AND METHODS: Fifteen patients with head and neck cancer and involved neck nodes were enrolled. Each patient took two sets of computerized tomography (CT) in the same position before and after intravenous CA injections. Target volumes and organs at risk (OAR) were contoured on the enhanced CT, and then an IMRT plan of nine equiangular beams with a 6 MV X-ray was created. After the fusion of non-enhanced and enhanced CTs, the contours and the IMRT plan created from the enhanced CT were copied and placed to the non-enhanced CT. Doses were calculated again from the non-enhanced CT by the same IMRT plan. The radiation doses calculated from the two sets of CTs were compared with regard to planning target volumes (PTV) and the three OARs, both parotid glands and the spinal cord, by Wilcoxon's signed rank test. RESULTS: The doses (maximum, mean, and the dose of 95% of PTV received (D95%)) of PTV70 and PTV59.4 calculated from the enhanced CTs were lower than those from the non-enhanced CTs (p < 0.05), but the dose differences were less than 1% compared to the doses calculated from the enhanced CTs. The doses of PTV50.4, parotid glands, and spinal cord were not significantly different between the non-enhanced and enhanced CTs. CONCLUSIONS: The difference between the doses calculated from the CTs with and without CA enhancement was tolerably small, therefore using intravenous CA could be recommended for the planning CT of head and neck IMRT.

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine.

AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m(2) on d 1 to 5 and cisplatin 60 mg/m(2) on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m(2) daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival.

Impact of intensity-modulated radiation therapy as a boost treatment on the lung-dose distributions for non-small-cell lung cancer.

PURPOSE: To investigate the feasibility of intensity-modulated radiotherapy (IMRT) as a method of boost radiotherapy after the initial irradiation by the conventional anterior/posterior opposed beams for centrally located non-small-cell lung cancer through the evaluation of dose distributions according to the various boost methods. METHODS AND MATERIALS: Seven patients with T3 or T4 lung cancer and mediastinal node enlargement who previously received radiotherapy were studied. All patients underwent virtual simulation retrospectively with the previous treatment planning computed tomograms. Initial radiotherapy plans were designed to deliver 40 Gy to the primary tumor and involved nodal regions with the conventional anterior/posterior opposed beams. Two radiation dose levels, 24 and 30 Gy, were used for the boost radiotherapy plans, and four different boost methods (a three-dimensional conformal radiotherapy [3DCRT], five-, seven-, and nine-beam IMRT) were applied to each dose level. The goals of the boost plans were to deliver the prescribed radiation dose to 95% of the planning target volume (PTV) and minimize the volumes of the normal lungs and spinal cord irradiated above their tolerance doses. Dose distributions in the PTVs and lungs, according to the four types of boost plans, were compared in the boost and sum plans, respectively. RESULTS: The percentage of lung volumes irradiated >20 Gy (V20) was reduced significantly in the IMRT boost plans compared with the 3DCRT boost plans at the 24- and 30-Gy dose levels (p = 0.007 and 0.0315 respectively). Mean lung doses according to the boost methods were not different in the 24- and 30-Gy boost plans. The conformity indexes (CI) of the IMRT boost plans were lower than those of the 3DCRT plans in the 24- and 30-Gy plans (p = 0.001 in both). For the sum plans, there was no difference of the dose distributions in the PTVs and lungs according to the boost methods. CONCLUSIONS: In the boost plans the V20s and CIs were reduced significantly by the IMRT plans, but in the sum plans the effects of IMRT on the dose distributions in the tumor and lungs, like CI and V20, were offset. Therefore, to keep the beneficial effect of IMRT in radiotherapy for lung cancer, it would be better to use IMRT as a whole treatment plan rather than as a boost treatment.

Stem cells expressing homing receptors could be expanded from cryopreserved and unselected cord blood.

We assessed the cytokine combinations that are best for ex vivo expansion of cord blood (CB) and the increment for cell numbers of nucleated cells, as well as stem cells expressing homing receptors, by an ex vivo expansion of cryopreserved and unselected CB. Frozen leukocyte concentrates (LC) from CB were thawed and cultured at a concentration of 1 x 10(5)/mL in media supplemented with a combination of SCF (20 ng/mL)+TPO (50 ng/mL)+FL (50 ng/mL)+/-IL-6 (20 ng/mL)+/-G-CSF (20 ng/mL). After culturing for 14 days, the expansion folds of cell numbers were as follows: TNC 22.3+/-7.8 approximately 26.3+/-4.9, CFU-GM 4.7+/-5.1 approximately 11.7+/-2.6, CD34+CD38- cell 214.0+/-251.9 approximately 464.1+/-566.1, CD34+CXCR4+ cell 4384.5+/-1664.7 approximately 7087.2+/-4669.3, CD34+VLA4+ cell 1444.3+/-1264.0 approximately 2074.9+/-1537.0, CD34+VLA5+ cell 86.2+/-50.9 approximately 113.2+/-57.1. These results revealed that the number of stem cells expressing homing receptors could be increased by an ex vivo expansion of cryopreserved and unselected CB using 3 cytokines (SCF, TPO, FL) only. Further in vivo studies regarding the engraftment after expansion of the nucleated cells, as well as the stem cells expressing homing receptors will be required.