A Technique to Deliver Conformal External Beam Radiation for Squamous Carcinoma of the Penile Glans and Urethra.

This study presents an approach to external beam radiation therapy for treating penile cancer using a small water bath. This modified technique involves the use of an acrylic, cuboid-shaped water bath with dimensions 6 × 6 × 8 cm3. The water bath is filled with readily available saline solution maintained at room temperature. The patient is positioned in the prone position, and the penis is placed within the water bath. The isocenter is set at the center of the water bath, and bilateral beams are positioned at 89.1° and 270.9°. The proposed technique was evaluated based on dose calculations, demonstrating a clinical target volume dose with a Dmax of 103.5% and a Dmin of 100.0% of the prescribed dose. Additionally, the method showed a low organs-at-risk dose, with a Dmean of only 1% for the testicles. The treatment zone inside the water bath also showed a uniform dose distribution. This technique not only offers high treatment efficiency and more accurate dose distribution to the targeted area but also provides additional benefits, including reduced toxicity to organs at risk and increased device utilization efficiency. In conclusion, the proposed modified external beam radiation therapy method presents a promising alternative for patients with penile cancer, enhancing treatment precision and safety.

Clinical Value of EZH2 in Hepatocellular Carcinoma and Its Potential for Target Therapy.

Background and objectives: EZH2 is overexpressed in hepatocellular carcinoma (HCC) and is correlated with poor prognosis. However, its clinical significance and molecular mechanism have not been studied in HCC. In this study, clinical and prognostic values of EZH2 was studied using Total Cancer Genome Atlas (TCGA) data and then, these data were confirmed in Huh1 and HepG2 cell lines. Materials and Methods: We used the TCGA database from cBioPortal. In addition, we analyzed EZH2 mRNA levels in HCC cell lines and its correlation with STAT3 and EZH2. Results: According to TCGA, EZH2 had a prognostic value in various cancers, especially in HCC. Furthermore, EZH2 in HCC was correlated with N stage (p = 0.045) and alpha-fetoprotein (AFP) > 20 ng/mL (p < 0.01). However, a negative association between EZH2 and age (p = 0.027) was found. The overall survival result of HCC was significantly poorer in patients with high EZH2 expression. In addition, the recurrence rate was also significantly higher in patients with high expression of EZH2 than those with low expression (χ2 = 16.10, p < 0.001). EZH2 expression was negatively correlated with STAT3 expression among EZH2-associated genes (R = -0.163, p = 0.002). EZH2 expression level was down-regulated to 50% or less compared to the control group treated negative siRNA. MTT assays showed that EZH2-siRNA affected on the viability of HCC cell line significantly. Conclusions: In conclusion, the overexpression of EZH2 was an independent biomarker for poor outcomes of HCC. However, more in vivo studies are required to identify the downstream target genes in HCC to improve our understanding of the biological role of EZH2 in HCC.

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy.

BACKGROUND: It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy. METHODS: We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups. RESULTS: After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045-0.966) and 0.460 (95% CI, 0.220-0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018). CONCLUSIONS: IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.

Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients.

PURPOSE: To report the early clinical outcomes of combining intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) in comparison with IMRT alone in treating oropharynx cancer (OPC) patients. MATERIALS AND METHODS: The medical records of 148 OPC patients who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center, were retrospectively reviewed. During the 5.5 weeks' RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity-score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. RESULTS: With the median follow-up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, the IMRT/IMPT combination group experienced grade ≥ 3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p < 0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p = 0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p = 0.021); and AQA in 47.4% and 21.1% (p = 0.016), respectively. In multivariate logistic regression, grade ≥ 3 mucositis was significantly less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.027 and 0.024, respectively). AQA score ≥ 3 was also less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.085 and 0.018, respectively). CONCLUSIONS: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.

Development of a Tongue Immobilization Device Using a 3D Printer for Intensity Modulated Radiation Therapy of Nasopharyngeal Cancer Patients.

PURPOSE: This study aimed to reduce radiation doses to the tongue, a patient-specific semi-customized tongue immobilization device (SCTID) was developed using a 3D printer for helical tomotherapy (HT) of nasopharyngeal cancer (NPCa). Dosimetric characteristics and setup stability of the SCTID were compared with those of a standard mouthpiece (SMP). MATERIALS AND METHODS: For displacement and robust immobilization of the tongue, the SCTID consists of four parts: upper and lower tooth stoppers, tongue guider, tongue-tip position guide bar, and connectors. With the SCTID and SMP, two sets of planning computed tomography and HT plans were obtained for 10 NPCa patients. Dosimetric and geometric characteristics were compared. Position reproducibility of the tongue with SCTID was evaluated by comparing with planned dose and adaptive accumulated dose of the tongue and base of the tongue based on daily setup mega-voltage computed tomography. RESULTS: Using the SCTID, the tongue was effectively displaced from the planning target volume compared to the SMP. The median mucosa of the tongue (M-tongue) dose was significantly reduced (20.7 Gy vs. 27.8 Gy). The volumes of the M-tongue receiving a dose of 15 Gy, 30 Gy, and 45 Gy and the volumes of the mucosa of oral cavity and oropharynx (M-OC/OP) receiving a dose of 45 Gy and 60 Gy were significantly lower than using the SMP. No significant differences was observed between the planned dose and the accumulated adaptive dose in any dosimetric characteristics of the tongue and base of tongue. CONCLUSION: SCTID can not only reduce the dose to the M-tongue and M-OC/OP dramatically, when compared to SMP, but also provide excellent reproducibility and easy visual verification.

Early clinical outcomes of helical tomotherapy/intensity-modulated proton therapy combination in nasopharynx cancer.

This study aimed to evaluate the feasibility of combining helical tomotherapy (HT) and intensity-modulated proton therapy (IMPT) in treating patients with nasopharynx cancer (NPC). From January 2016 to March 2018, 98 patients received definitive radiation therapy (RT) with concurrent chemotherapy (CCRT). Using simultaneous integrated boost and adaptive re-plan, 3 different dose levels were prescribed: 68.4 Gy in 30 parts to gross tumor volume (GTV), 60 Gy in 30 parts to high-risk clinical target volume (CTV), and 36 Gy in 18 parts to low-risk CTV. In all patients, the initial 18 fractions were delivered by HT, and, after rival plan evaluation on the adaptive re-plan, the later 12 fractions were delivered either by HT in 63 patients (64.3%, HT only) or IMPT in 35 patients (35.7%, HT/IMPT combination), respectively. Propensity-score matching was conducted to control differences in patient characteristics. In all patients, grade ≥ 2 mucositis (69.8% vs 45.7%, P = .019) and grade ≥ 2 analgesic usage (54% vs 37.1%, P = .110) were found to be less frequent in HT/IMPT group. In matched patients, grade ≥ 2 mucositis were still less frequent numerically in HT/IMPT group (62.9% vs 45.7%, P = .150). In univariate analysis, stage IV disease and larger GTV volume were associated with increased grade ≥ 2 mucositis. There was no significant factor in multivariate analysis. With the median 14 month follow-up, locoregional and distant failures occurred in 9 (9.2%) and 12 (12.2%) patients without difference by RT modality. In conclusion, comparable early oncologic outcomes with more favorable acute toxicity profiles were achievable by HT/IMPT combination in treating NPC patients.

Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer.

PURPOSE: This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer. MATERIALS AND METHODS: Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course. RESULTS: The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED10) (≥ 79.2 Gy10 vs. < 79.2 Gy10; hazard ratio [HR], 0.431), smaller CTV (≤ 80 cm3 vs. > 80 cm3; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS. CONCLUSION: The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED10, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

Clinical significance of the lymph node ratio in N1 breast cancer.

PURPOSE: The purpose of this study was to evaluate the prognostic value of the lymph node ratio (LNR), which was defined as the proportion of involved nodes of all dissected nodes, in pN1 breast cancer. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of patients with pN1 breast cancer (N = 144) treated at Keimyung University Dongsan Medical Center, Daegu, Korea between 2001 and 2010. The median age was 46 years (range, 27 to 66 years). The LNR was 0.01-0.15 (low LNR) in 130 patients and >0.15 (high LNR) in 14 patients. Sixty-five patients (45.1%) had T1 tumors, 74 (51.4%) had T2 tumors, and 5 (3.5%) had T3 tumors. Eighty-eight patients (61.1%) underwent total mastectomy and 56 (38.9%) underwent partial mastectomy. Fifty-nine patients (41.0%) underwent radiotherapy and 12 (8.3%) underwent regional radiotherapy. The median follow-up period was 65 months. RESULTS: The 5- and 10-year disease-free survival (DFS) rates were 92.7% and 82.4%, respectively. Univariate analyses revealed that high LNR (p = 0.004), total mastectomy (p = 0.006), no local radiotherapy (p = 0.036), and stage T2 or T3 (p = 0.010) were associated with worse DFS. In multivariable analysis, only high LNR (p = 0.015) was associated with worse DFS. CONCLUSION: High LNR is an independent prognostic factor in pN1 breast cancer and could be an indication for adjuvant radiotherapy in these patients.

Is Prophylactic Irradiation to Para-aortic Lymph Nodes in Locally Advanced Cervical Cancer Necessary?

PURPOSE: This study evaluated the efficacy of extended field irradiation (EFI) in patients with locally advanced cervical cancer without para-aortic nodal involvement. MATERIALS AND METHODS: A total of 203 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stage, IB2-IIIB) treated with radiotherapy at Keimyung University Dongsan Medical Center from 1996 to 2010 were retrospectively analyzed. The median patient age was 59 years (range, 29 to 83 years). None of the patients had para-aortic node metastases. Of the 203 patients, 88 underwent EFI and 115 underwent irradiation of the pelvis only. Concurrent chemoradiotherapy (CCRT) was administered to 133 patients. EFI field was used for treatment of 26 patients who received radiotherapy alone and 62 who received CCRT. RESULTS: The median follow-up period was 60 months. The 2- and 5-year overall survival (OS) rates were 87.8% and 73.5%, respectively, and the 2- and 5-year disease-free survival rates were 81.7% and 75.0%, respectively, however, no survival differences were observed between the two treatment field groups. EFI tended to increase OS in the radiotherapy alone group, but not in the CCRT group. CONCLUSION: These findings suggest that EFI does not have a significant effect in patients with locally advanced cervical cancer, especially in patients receiving CCRT. Conduct of additional studies will be required in order to confirm these findings.

Postoperative radiotherapy for endometrial cancer.

PURPOSE: To investigate the prognostic factors and effectiveness of postoperative radiotherapy alone for endometrial carcinoma. MATERIALS AND METHODS: Sixty four patients with stage I-III endometrial cancer (EC) treated with postoperative radiotherapy alone between January 1989 and December 2008 at the Keimyung University Dongsan Medical Center were chosen for the present study. Typically, total hysterectomy, salpingo-oophorectomy and lymphadenectomy were performed on the patient's pelvis. Total dose from 50.4 Gy to 63 Gy was irradiated at pelvis or extended field. Thirteen patients were treated with Co-60 or Ir-192 intracavitary radiotherapy. Follow-up periods were from 7 to 270 months, with a median of 56 months. RESULTS: Five year overall survival (OS) rate was 58.7%, respectively. Five year disease-free survival (DFS) rate was 59.2%, respectively. In univariate analysis for OS and DFS, stage, menopausal age, type of operation, serosal invasion, and lymph node involvement were found to be statistically significant. Histologic type was marginally significant. In multivariate analysis for OS and DFS, stage, types of operation, histologic type were also found to be statistically significant. Treatment failure occurred in 14 patients. The main pattern of failure was found to be distant metastasis. Time to distant metastasis was from 3 to 86 months (median, 12 months). There were no grade 3 or 4 complications. CONCLUSION: Stage, types of operation, and histologic type could be the predictive prognostic factors in patients. We contemplated postoperative radiation as effective and safe treatment method for EC. Additional treatment would be needed to reduce distant metastasis.

Interval between Surgery and Radiation Therapy Is an Important Prognostic Factor in Treatment of Rectal Cancer.

PURPOSE: The purpose of this study is to evaluate survival and prognostic factors for rectal cancer, including interval between surgery and radiation therapy after surgery, radiation therapy, and chemotherapy. MATERIALS AND METHODS: We conducted a retrospective study of 153 patients with rectal cancer who were treated with surgery, radiotherapy with/without chemotherapy at Keimyung University Dongsan Medical Center from January, 1988 to December, 2005. The study included 89 males and 64 females, with a median age of 56 years (range, 23 to 81 years). Tumor, node and metastasis (TNM) was I in 23 patients, II in 39, and III in 91. Radiation therapy was performed on pelvic fields using a median dose of 54 Gy five days per week, 1.8 Gy once per day. Ninety two patients were treated with radiotherapy, 43 with concurrent chemo-radiation therapy and 18 with sequential therapy after surgery. The median follow-up period was 52 months (range, 4 to 272 months). The interval between surgery and radiation was 1-25 weeks (median, 5 weeks). RESULTS: Two-year and five-year overall survival rate was 64.7% and 46.4%, respectively. Two-year and five-year disease-free-survival (DFS) rate was 58.6% and 43.1%, respectively. Median DFS was 39 months. Loco-regional failure was evident in 10.5% of patients, 8.4% had distant metastasis, and 9.2% had both. In multivariate analysis, TNM stage and interval between surgery and radiation therapy (≤5 weeks vs. >5 weeks; 95% confidence interval, 1.276 to 2.877; hazard ratio, 1.916; p=0.002) were significant prognostic factors of DFS. CONCLUSION: Survival rates for rectal cancer after surgery, chemotherapy, and radiation therapy were similar to those reported in previous studies. Starting radiation therapy as soon as possible after surgery, especially within the first five weeks after surgery, is suggested.

Effect of the urease accessory genes on activation of the Helicobacter pylori urease apoprotein.

The roles that accessory gene products play in activating the Helicobacter pylori urease apoprotein were examined. The activity of the urease apoprotein increased in the following order when it was expressed with the accessory genes: ureG