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Background: There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer., Methods: This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991)., Results: Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5-21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications., Conclusions: Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period.

Aim: To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC)., Methods: We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed., Results: Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 ( P = 0.001), complete circumference involvement ( P < 0.0001), stenosis at diagnosis ( P = 0.024), and endoscopic complete response ( P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis ( P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement ( P = 0.023), stenosis at diagnosis ( P < 0.0001), and occurrence of post-RT stenosis or TEF ( P < 0.001) in univariate analysis, while stenosis at diagnosis ( P = 0.004) and occurrence of post-RT stenosis or TEF ( P = 0.023) were significant in multivariate analysis., Conclusion: Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.

Purpose: The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC)., Materials and Methods: We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions., Results: The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy 10 vs. 56.3 Gy 10 ). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT., Conclusion: Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival., Competing Interests: relevant to this article was not reported.

In patients with head and neck cancer treated with radiation therapy, the choice of which neck levels require elective radiation can dramatically influence the risk of regional failure and may contribute to cancer mortality and overall survival. Retrospective evaluation of elective nodal coverage in previously treated patients with head and neck cancer is a time intensive and, in most cases, subjective process. In order to objectively assess the extent of lymph node irradiation in large cohorts of patients, automated objective methods to assess elective lymph node treatment are crucial. In this work, we demonstrate a novel approach using a convolutional neural network (CNN) to autosegment, retrospectively label, and classify the extent of elective neck irradiation in previously treated patients. Initially, 100 patients with head and neck cancer were contoured to identify all elective neck level targets as per standard guidelines1, including levels IA, IB, II, III, IV, V, VIIA on both left and right necks. These patients were used to train a CNN neck level model (NLM) which was validated on a further 10 patients clinically. After training, the resultant NLM was applied retrospectively to all patients in the RADCURE dataset2. Overlap between the autosegmented NLM model contours with existing elective neck CTV targets was assessed using the proportion of voxel overlap of the individual neck structures with the elective CTV which was clinically defined. Primary tumor laterality as assessed in the clinical database was used to normalize right and left neck targets to ipsilateral and contralateral relative to the primary tumor. Neck levels were assumed to be 'treated' if >70% of the auto-segmented volume was overlapped with the clinical elective CTV target in the respective neck. Summary statistics were calculated by disease site, tumor volume, staging information, and clinical variables to evaluate patterns of CTV coverage and associations with tumor or patient factors. A total of 1,748 patients within the RADCURE dataset were included in the analysis as they had the primary tumor laterality defined clinically. After NLM application, comprehensive neck irradiation (IA-VIIA) occurred in 33%, 55%, 31%, 16%, 14%, and 12% of patients with oropharynx, nasopharynx, hypopharynx, larynx, oral cavity, and paranasal/nasal primary disease sites, respectively. Within primary disease sites, the proportion of the entire elective neck (IA-VII) which was included in the elective target volume varied substantially within sites but also showed expected differences in elective neck treatment (Figure) with nasopharynx representing the most comprehensive approach and nasal and salivary glands the least comprehensive approaches. Important patterns of elective treatment were visible with variations in specific levels of treatment related to primary site evident in the objective classifications of levels IA, II, and the retropharyngeal (VIIA) nodes. (Table). Specifically, coverage of level IA was rare, but more common in patients with lip/oral cavity or paranasal/nasal primary site. In patients with oropharyngeal primary disease, contralateral level II overlap showed approximately 12% of oropharynx patients were treated with ipsilateral intent only consistent with our previous reports from our institution.3 Retropharyngeal lymph node coverage was highest in the patients with nasopharyngeal disease, but identified a critical variation in contouring whereby a subset of patients did not have a formal elective VIIA target and instead relied on the overlap of primary site CTVs to ensure coverage of these regions. [Display omitted] Automatic assessment of elective neck coverage using a neck level auto-segmentation model shows substantial (but anticipated) variation in elective neck coverage based on disease site. Objective methods to interrogate target volumes and the resultant plan information will allow more detailed analysis and understanding of patterns of failure following radiation therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The recent advancement to RadCalc version 7.1.4 marks a significant milestone as an independent dose verification tool tailored to encompass both mechanical and dosimetric intricacies of MR-linacs. Although previous assessments successfully validated the software's efficacy on a 0.35 T MR-linac using v7.1.4, its validation for a 1.5 T MR-linac was restricted to v6.3. This discrepancy prompted an investigation into the software's performance on a 1.5 T MR-linac due to the absence of a specific MR-linac beam-modeling protocol within RadCalc. This study's novelty lies in the rigorous evaluation of calculation accuracy utilizing diverse beam-modeling techniques for the 1.5 T MR-linac. Results of this comprehensive analysis, showcasing RadCalc's calculated doses and their alignment with expected measurements, robustly affirm its credibility and accuracy in dose calculations, particularly within the complex setting of the 1.5 T magnetic field. The purpose of this study is to evaluate RadCalc, an independent dose verification software, for patient-specific quality assurance (PSQA) in online adaptive planning with a magnetic resonance linear accelerator (MR-linac) of a 1.5 T. Version 7.1.4 of RadCalc to introduce the capability to establish a beam model that incorporates MR field characteristics. A total of six models were established, with one using manufacturer-provided data and the others differing in percentage depth dose (PDD) data sources. Overall, two models utilized PDD data from the treatment planning system (TPS), and three used commissioned PDD data from gantry angles of 0° and 270°. Simple tests on a virtual water phantom assessed dose-calculation accuracy, revealing percentage differences ranging from −0.5% to −20.6%. Excluding models with significant differences, clinical tests on 575 adaptive plans (prostate, liver, and breast) showed percentage differences of −0.51%, 1.12%, and 4.10%, respectively. The doses calculated using RadCalc demonstrated similar trends to those of the PSQA-based measurements. The newly released version of RadCalc enables beam modeling that considers the characteristics of the 1.5 T magnetic field. The accuracy of the software in calculating doses at 1.5 T magnetic fields has been verified, thereby making it a reliable and effective tool for PSQA in adaptive plans. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is gaining attention as a poor prognostic factor for various types of malignancies. This study evaluated the prevalence and prognostic significance of sarcopenia and its association with survival in hepatocellular carcinoma (HCC) patients who underwent radiotherapy (RT) to the primary site. Materials and Methods: Between January 2009 and November 2016, 156 patients with HCC that underwent RT to the liver were retrospectively studied. Sarcopenia was defined as an L3 skeletal muscle index of <49 cm2/m2 for men and <41 cm2/m2 for women as proposed by Korean-specific cut-off value. Sarcopenia was identified pre- and post-RT (within 3 months from the end of RT). Results: Pre-RT sarcopenia occurred in 99 (63.5%) patients and was significantly associated with higher levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II), lower percentage of overweight/obesity (body-mass index), higher percentage of previous systemic chemotherapy, and lower total RT dose. At a median follow-up of 9.3 months, median overall survival (OS) was significantly lower in patients with pre-RT sarcopenia than in those without (7.1 vs. 15.3 months, p < 0.001). In multivariate analysis [reporting hazard ratio (HR): 95% confidence interval (CI)], albumin-bilirubin score (2.35: 1.33–4.17; p = 0.003), total dose (0.44: 0.27–0.71; p = 0.001), and pre-RT sarcopenia (2.38: 1.53–3.70; p < 0.001) were independent OS prognostic factors. Among patients without pre-RT sarcopenia, 20 newly developed sarcopenia after RT and showed significantly lower OS compared to those without sarcopenia after RT (n = 35) (median 14.1 vs. 17.5 months, p = 0.018). Multivariate logistic regression analysis [reporting odds ratio (OR)] demonstrated older age (310.190; p = 0.007), Child-Pugh classification B or C (15.239; p = 0.047), higher alpha-fetoprotein (128.486; p = 0.008), higher PIVKA-II (118.536; p = 0.027), and larger planning target volume (51.310; p = 0.026) as significant factors for newly developed post-RT sarcopenia. Conclusion: Newly developed sarcopenia after RT, as well as pre-RT sarcopenia, were associated with poor survival for HCC patients who underwent RT to the liver. This result suggests the possibility that early intervention such as nutritional support and exercise therapies before and during RT could prevent muscle wasting and may be effective in improving the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Salvage treatment including surgery and radiotherapy (RT) for recurrent or progressive meningioma is not an easy task, especially for the skull base location. And yet, criteria for adjuvant radiotherapy after initial surgery are not clearly defined for WHO grade I/II meningioma. We determined prognostic factors for recurrence and evaluated the benefit of risk group-adapted adjuvant RT for WHO grade I/II meningioma in the skull base. Methods: We reviewed 272 patients who underwent surgery and were pathologically confirmed with WHO grade I or II skull base meningioma between January 2000 and July 2017. Subgroup analyses were performed for WHO grade I (259 patients) and WHO grade II (13 patients) meningiomas to evaluate the benefit of RT in each subgroup. Results: Patients with WHO grade II meningiomas tended to present more neurologic symptoms and to receive RT more frequently. In prognostic factor analysis, tumor size (p = 0.039), surgical extent (p < 0.001), and RT (p = 0.005) were associated with recurrence-free survival (RFS). In subgroup analysis of WHO grade I, RFS was significantly better in RT group after matching other variables. The risk stratification was performed using three risk factors (petroclival location, tumor size, Simpson grade) in WHO grade I patients, and significantly different RFS was observed according to the risk group in non-RT patients. Conclusions: Tumor size, Simpson grade, and adjuvant RT were prognostic factors. The risk group-adapted approach can facilitate the selection of patients who may benefit from adjuvant RT for WHO grade I/II skull base meningiomas. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiation therapy (CCRT) followed by hepatic arterial infusional chemotherapy (HAIC) was reported to be effective for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. However, transarterial chemoembolization (TACE) is not preferred in this setting. The aim of this study was to assess the factors affecting survival after CCRT, including additional TACE during repeated HAIC.Methods: Thirty-eight patients who underwent CCRT as the initial treatment for Barcelona Clinic Liver Cancer stage C HCC with vascular invasion between 2009 and 2016 were reviewed retrospectively. During CCRT, 5-fluorouracil (5-FU) was infused via chemoport during the first and last five days of five weeks of external beam radiation therapy. After CCRT, repeated HAIC with cisplatin and 5-FU was performed monthly. Nineteen patients (50%) underwent additional TACE between repeated HAICs. Factors related to overall survival and progression free survival (PFS) were analyzed.Results: The mean age of patients was 55 years (male:female, 33:5). Underlying liver diseases were hepatitis B, hepatitis C and non-B/C in 29, 1 and 8 patients, respectively. The median radiation dose was 4500 cGy. The objective response (OR) rate at one months after CCRT was 36.8%. The median PFS was 7.4 (range, 1.8 - 32.1) months. The median overall survival was 11.6 (range 2.8-65.7) months. Achieving an OR after CCRT (hazard ratio [HR], 0.028; P < 0.001), additional TACE (HR, 0.134, P < 0.001), and further rounds of HAIC (HR, 0.742, P = 0.001) were independent significant factors related to overall survival. The overall survival duration of patients with an OR after CCRT (median 44.2 vs. 6.6 months, P < 0.001) and additional TACE (median 19.8 vs. 9.1 months, P = 0.001) were significantly greater than those without an OR after CCRT or additional TACE.Conclusion: Patients who achieved an OR after CCRT, underwent additional TACE, and were subjected to repeated rounds of HAIC following CCRT showed better survival after CCRT for advanced stage of HCC with vascular invasion. A further prospective study is needed to confirm the positive effect of additional TACE after CCRT. [ABSTRACT FROM AUTHOR]

Background & Aims This nationwide, multicenter study investigated treatment outcomes as well as the optimal radiotherapeutic strategy in patients with hepatocellular carcinoma ( HCC) and portal vein tumour thrombosis ( PVTT). Methods We retrospectively reviewed the records of 985 patients who received radiotherapy ( RT) for PVTT. The median equivalent RT dose was 48.75 Gy. Combined treatment, defined as liver-directed treatments performed within a month of RT, was administered to 657 patients (66.7%). The PVTT and primary tumour were irradiated in 413 patients (41.9%), and PVTT only was targeted in 572 patients (58.1%). Results The response rate of the PVTT was 51.8%, and RT responders had a significantly longer survival than non-responders (15.2 vs. 6.9 months). Equivalent RT dose and combined treatment predicted response of PVTT. The median overall survival ( OS) was 10.2 months. Multivariate analysis revealed the equivalent RT dose ˃45 Gy and combined treatment as significant positive factors for OS. In the propensity score matching analysis, the combined treatment group had better OS than the no combined treatment group, whereas the OS of the PVTT + primary tumour group did not differ significantly from that of the PVTT only group. Conclusion The equivalent RT dose ˃45 Gy, given in combination with other treatments, provided better PVTT control and OS. The optimal RT volume is suggested for either PVTT + primary or PVTT only. Taken together, multimodal treatment with equivalent RT dose higher than 45 Gy is recommended for patients with HCC and PVTT. [ABSTRACT FROM AUTHOR]

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Background and Aims Optimal response criteria and assessment timing were investigated through radiologic-pathologic correlation in hepatocellular carcinoma (HCC) treated with localized chemoradiotherapy (CRT). Methods We reviewed 19 consecutive HCC patients who underwent surgical resection after radiotherapy and concurrent hepatic arterial infusion chemotherapy. Patients who received transarterial chemoembolization before RT or surgery were excluded from evaluation. Tumor diameters and total and enhancing tumor volumes were measured from CT images obtained 1, 3, 6, and 9 months after CRT. Percent changes calculated using size (RECIST and WHO) and enhancement criteria (mRECIST and EASL) were correlated with percent changes in total and enhancing tumor volumes, and with percent viable tumor in surgical specimens. Results Median time between CRT and resection was 4.1 months (range, 1.5-15.4 months). CR and PR rates were 0 and 68% by RECIST, 0 and 63% by WHO, 53% and 37% by mRECIST, and 53% and 42% by EASL. Pathologic CR (pCR) rate was 52.6%. Radiologic criteria showed strong correlation with tumor volumes at 1 and 3 months after CRT; at 6 months, however, size and enhancement criteria showed strong correlation only with total and enhancing tumor volumes, respectively. Enhancement criteria were better predictors of pathologic response at all times including preoperative evaluation (RECIST: R2 = 0.303, P = 0.015 and WHO: R2 = 0.366, P = 0.006 vs. mRECIST: R2 = 0.760, P < 0.0001 and EASL: R2 = 0.768, P < 0.0001). Time interval >6 months before resection showed significant correlation with pCR ( P = 0.013). Conclusions We recommend using enhancement criteria in assessing tumor viability, especially if the tumor was to be resected <6 months after CRT. [ABSTRACT FROM AUTHOR]

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm 2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. [ABSTRACT FROM AUTHOR]

Background/Aim: Little is known about the patterns of treatment failure following definitive chemoradiotherapy (CCRT), especially in esophageal squamous cell carcinoma (SCC). We evaluated definitive CCRT failure patterns and determined the predictive factors for treatment response in esophageal SCC. Methods: We evaluated 136 consecutive patients with esophageal SCC treated with definitive CCRT. We evaluated the factors associated with complete remission (CR) after CCRT and analyzed the pattern of treatment failure of recurred patients and incomplete remission patients. The failures were categorized as either within (locoregional failure) or outside the radiation field (out-field failure). Results: Fifty-seven patients achieved CR after CCRT. Consolidation chemotherapy was significantly associated with CR. Only 4 (7.0%) patients had CR after CCRT in patients with M1a node (Celiac or subclavian lymph nodes involvement by 6th AJCC). During follow-up, 74 patients (54.4%) experienced locoregional failure, 26 (19.1%) out-field failure, and 35 (25.7%) no failure. Esophageal obstruction prior to CCRT, residual tumor according to the first follow-up endoscopy, and poor follow-up computed tomography responses were significantly associated with locoregional failure. Conclusion: Approximately 70% of treatment failures were local failures. Future therapeutic strategies need to focus on improving local control to increase treatment outcomes of CCRT. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions was prescribed as planning target volume (PTV) 1 at dose level 1. The dose escalation was 0.2 Gy per fraction and up to 2.5 Gy, with 62.5 Gy at level 3. Concurrent intra-arterial 5-fluorouracil was administered during the first and fifth weeks of radiotherapy (RT). Toxicities were graded using the Common Toxicity Criteria for Adverse Events, version 4.0. Results: Seventeen patients with HCC were analyzed: four at dose level 1, 6 at level 2, and 7 at level 3. The mean irradiated dose administered to the uninvolved liver at each dose level was 21.3, 21.6, and 18.2 Gy, respectively. There was no grade ≥3 gastrointestinal toxicity; two patients experienced grade 3 hyperbilirubinemia. All patients had Child-Pugh class A disease, but 3 patients developed class B disease after iA-CCRT. During a median follow-up of 13 months, the median progression-free survival (PFS) and overall survival (OS) were 10 and 22 months, respectively. Patients treated at dose level 3 showed improved PFS and OS. Conclusions: Radiation dose escalation of iA-CCRT did not cause any significant toxicities in patients with advanced HCC. Further large-scale studies with long-term follow-up are needed to determine the efficacy and feasibility of higher doses of iA-CCRT. [ABSTRACT FROM AUTHOR]

A response by Jung Ho Im and colleagues to a letter to the editor about their article "Is Radiotherapy the Best Option for Treating Hepatocellular Carcinoma With PVTT" in the 2017 issue is presented.

Background: The current standard treatment for resectable pancreatic cancer is surgical resection followed by adjuvant chemotherapy. Local recurrence rates are high even after curative resection; thus, the long-term outcome of locally advanced pancreatic cancer remains poor. Intraoperative radiotherapy (IORT) uses a low-energy x-ray source to deliver a single fraction of high-dose radiation to the tumor bed during a surgical procedure, while effectively sparing the surrounding normal tissues. IORT has the potential to improve the efficacy of radiation therapy for pancreatic cancer.Methods/design: This prospective, one-armed, phase II study will investigate the role of IORT in improving local control in patients with resectable pancreatic adenocarcinoma. The patients will receive surgery and IORT of 10 Gy prescribed at a 5-mm depth of the tumor bed, followed by adjuvant gemcitabine chemotherapy according to the current standard of care. The aim is to enroll 42 patients.Discussion: The primary endpoint of this trial is to evaluate the feasibility of IORT and the local recurrence rate after one year. The secondary endpoints include the acute and late toxicities, and disease-free survival and overall survival rates.Trial Registration: The trial was prospectively registered at Clinicaltrials.gov NCT03273374 on September 6, 2017. [ABSTRACT FROM AUTHOR]

Background: To investigate the prognostic value of pre-treatment neutrophil/lymphocyte ratio (NLR) in patients treated with definitive radiotherapy (RT) for head and neck cancer. Methods: We retrospectively analyzed 621 patients who received definitive RT for nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer. An NLR cut-off value of 2.7 was identified using a receiver operating characteristic curve analysis, with overall survival (OS) as an endpoint. Results: The 5-year progression-free survival (PFS) and OS for all patients were 62.3% and 72.1%, respectively. The patients with a high NLR (68%) had a significantly lower 5-year PFS and OS than their counterparts with a low NLR (32%) (PFS: 39.2% vs. 75.8%, p < 0.001; OS: 50.9% vs. 83.8%, p < 0.001). In a subgroup analysis according to primary site, a high NLR also correlated with a lower PFS and OS, except in oropharyngeal cancer, where a high NLR only exhibited a trend towards lower survival. In a multivariate analysis, a high NLR remained an independent prognostic factor for PFS and OS. Conclusion: Head and neck cancer tends to be more aggressive in patients with a high NLR, leading to a poorer outcome after RT. The optimal therapeutic approaches for these patients should be reevaluated, given the unfavorable prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Recently, cells deficient in O6-methylguanine–DNA methyltransferase (MGMT) were found to show increased sensitivity to temozolomide (TMZ). We evaluated whether hypermethylation of MGMT was associated with survival in patients with glioblastoma multiforme (GBM). Methods and Materials: We retrospectively analyzed 93 patients with histologically confirmed GBM who received involved-field radiotherapy with TMZ from 2001 to 2008. The median age was 58 years (range, 24–78 years). Surgical resection was total in 39 patients (42%), subtotal in 30 patients (32%), and partial in 17 patients (18%); only a biopsy was performed in 7 patients (8%). Postoperative radiotherapy began within 3 weeks of surgery in 87% of the patients. Radiotherapy doses ranged from 50 to 74 Gy (median, 70 Gy). MGMT gene methylation was determined in 78 patients; MGMT was unmethylated in 43 patients (55%) and methylated in 35 patients (45%). The median follow-up period was 22 months (range, 3–88 months) for all patients. Results: The median overall survival (OS) was 22 months, and progression-free survival (PFS) was 11 months. MGMT gene methylation was an independently significant prognostic factor for both OS (p = 0.002) and PFS (p = 0.008) in multivariate analysis. The median OS was 29 months for the methylated group and 20 months for the unmethylated group. In 35 patients with methylated MGMT genes, the 2-year and 5-year OS rates were 54% and 31%, respectively. Six patients with combined prognostic factors of methylated MGMT genes, age ≤50 years, and total/subtotal resections are all alive 38 to 77 months after operation, whereas the median OS in 8 patients with unmethylated MGMT genes, age >50 years, and less than subtotal resection was 13.2 months. Conclusion: We confirmed that MGMT gene methylation is a potent prognostic factor in patients with GBM. Our results suggest that early postoperative radiotherapy and a high total/subtotal resection rate might further improve the outcome. [Copyright &y& Elsevier]

Purpose: The purpose of this study was to analyze tumor heterogeneity based on tumor extent and suggest reappraisal of the system of the International Federation of Gynecology and Obstetrics (FIGO) for Stage III carcinoma of the uterine cervix from a radiotherapeutic viewpoint. Methods and Materials: Between 1986 and 2004, 407 patients with FIGO Stage III (FIGO Stage IIIa in 19 and IIIb in 388) were treated with external beam radiotherapy (RT) and high–dose rate brachytherapy. All patients were reviewed with respect to tumor extent. Patterns of failure and survival parameters were analyzed by use of the χ2 test and Kaplan-Meier method. Results: The complete response rate was 79.6%, and the 5-year overall survival rates for Stage IIIa and Stage IIIb carcinoma of the cervix were 82.1% and 54.8%, respectively. To determine which parameters of tumor extent had an influence on prognosis for Stage IIIb patients, pelvic wall (PW) extension and hydronephrosis (HD) retained significance on multivariate analysis. Stage IIIb patients were divided into three subgroups according to PW extension and HD: low risk (unilateral PW extension without HD), intermediate risk (HD without PW extension or bilateral PW extension without HD), and high risk (unilateral or bilateral PW extension with HD). The high-risk group had a remarkably low complete response rate, high locoregional failure rate, and low 5-year survival rate compared with the intermediate- and low-risk groups. Conclusions: FIGO Stage III carcinoma of the cervix covers considerably heterogeneous subgroups according to tumor extent. Before initiation of treatment, we suggest that physicians determine a tailored treatment policy based on tumor heterogeneity for each Stage III patient. [Copyright &y& Elsevier]