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Purpose: To analyze patterns of failure according to treatment modalities and evaluate the adequacy of an institution's current volume of postoperative radiotherapy (PORT) for World Health Organization (WHO) grade II or III meningiomas., Patients and Methods: Data of 98 patients treated by either surgery and PORT (PORT group, n = 53) or surgery alone (surgery group, n = 45) between March 2000 and December 2013 were reviewed. Clinical target volume of PORT was delineated as a 1.5-2-cm expansion from the tumor bed. Local failure (LF) was defined as recurrence within a 2-cm margin from the tumor bed. Failures other than LF were defined as out-field failure (OFF). Median total dose of PORT was 59.4 (range 45.0-69.0) Gy., Results: The PORT group had larger proportions of grade III meningiomas (18/53, 34.0%) than the surgery group (8/46, 15.6%) (p = 0.037). After a median 73.4-month follow-up, 29 patients experienced LF and 5 developed OFF. The actuarial 5-year local control (LC) rates were 86.7% and 59.3% in the PORT and surgery groups, respectively (p = 0.002). PORT was a significant factor of LC in the univariate (p = 0.003, hazard ratio [HR] 3.449, 95% confidence interval [CI] 1.516-7.846) and multivariate analyses (p < 0.001, HR 5.486, 95% CI 2.178-13.820)., Conclusions: Despite the larger proportion of grade III meningiomas in the PORT group, PORT reduced LF in patients with WHO grade II or III meningiomas compared with the surgery group. The current PORT field seems reasonable because LF was the dominant pattern of failure in patients treated by surgery alone.

Aim: To evaluate whether the retention rate of indocyanine green 15 min after administration (ICG-R15) could predict radiation hepatotoxicity in patients treated with radiotherapy (RT) for hepatocellular carcinoma (HCC)., Methods: We retrospectively reviewed data of 146 HCC patients treated with RT between February 1994 and December 2008. The ICG-R15 was measured within 1 month prior to the start of RT. Radiation hepatotoxicity was evaluated by incidence of radiation-induced liver disease (RILD) between 2 weeks and 3 months after completion of RT. We analysed the correlation between the incidence rate of RILD and the ICG-R15 before RT (pre-RT ICG-R15)., Results: The classic and non-classic RILD occurred in 15 patients (10.3%): classic type in five patients (3.4%) and non-classic RILD in 10 patients (6.9%). A positive correlation was shown between the probability of RILD and increase in pre-RT ICG-R15 (P < 0.0001). Univariate analysis indicated that cut-off value of pre-RT ICG-R15 could predict RILD significantly. The incidence of RILD for the patients with 22% or higher pre-RT ICG-R15 levels was 40.7% as compared to 3.4% for those with levels lower than 22% (P < 0.0001). There was no clinical factor that significantly affected RILD in univariate analysis. Multivariate analysis indicated that the pre-RT ICG-R15 value was the only significant factor affecting RILD (P < 0.0001)., Conclusion: These results suggest that pre-RT ICG-R15 could be a useful factor in predicting radiation hepatotoxicity in HCC patients treated with RT., (© 2012 John Wiley & Sons A/S.)

Background: Choosing the most effective approach for treating rectal cancer with mesorectal fascia (MRF) involvement or closeness and synchronous distant metastases is a current clinical challenge. The aim of this retrospective study was to determine if upfront systemic chemotherapy and short-course radiotherapy (RT) with delayed surgery enables R0 resection., Methods: Between March 2009 and October 2009, six patients were selected for upfront chemotherapy and short-course RT (5 × 5 Gy) with delayed surgery. The patients had locally advanced primary tumors with MRF involvement or closeness, as well as synchronous and potentially resectable distant metastases. Chemotherapy was administered to five patients between the end of the RT and surgery. All patients underwent total mesorectal excision (TME)., Results: The median patient age was 54 years (range 39-63). All primary and metastatic lesions were resected simultaneously. The median duration between short-course RT and surgery was 13 weeks (range, 7-18). R0 resection of rectal lesions was achieved in 5 patients. One patient, who had a very low-lying tumor, had an R1 resection. The median follow-up duration for all patients was 16.7 months (range, 15.5-23.5). One patient developed liver metastasis at 15.7 months. There have been no local recurrences or deaths., Conclusions: Upfront chemotherapy and short course RT with delayed surgery is a valuable alternative treatment approach for patients with MRF involvement or closeness of rectal cancer with distant metastases.

Purpose The Korean Society of Pediatric Neuro-Oncology (KSPNO) conducted treatment strategies for children with medulloblastoma (MB) by using alkylating agents for maintenance chemotherapy or tandem high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) according to the risk stratification. The purpose of the study was to assess treatment outcomes and complications based on risk-adapted treatment and HDC. Materials and Methods Fifty-nine patients diagnosed with MB were enrolled in this study. Patients in the standard-risk (SR) group received radiotherapy (RT) after surgery and chemotherapy using the KSPNO M051 regimen. Patients in the high-risk (HR) group received two and four chemotherapy cycles according to the KSPNO S081 protocol before and after reduced RT for age following surgery and two cycles of tandem HDC with ASCR consolidation treatment. Results In the SR group, 24 patients showed 5-year event-free survival (EFS) and overall survival (OS) estimates of 86.7% (95% confidence interval [CI], 73.6 to 100) and 95.8% (95% CI, 88.2 to 100), respectively. In the HR group, more infectious complications and mortality occurred during the second HDC than during the first. In the HR group, the 5-year EFS and OS estimates were 65.5% (95% CI, 51.4 to 83.4) and 72.3% (95% CI, 58.4 to 89.6), respectively. Conclusion High intensity of alkylating agents for SR resulted in similar outcomes but with a high incidence of hematologic toxicity. Tandem HDC with ASCR for HR induced favorable EFS and OS estimates compared to those reported previously. However, infectious complications and treatment-related mortalities suggest that a reduced chemotherapy dose is necessary, especially for the second HDC. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to identify the role of radiotherapy (RT) in the treatment of thymic carcinoma as well as the optimal RT target volume. A total of 116 patients who received multimodal treatment including RT with or without surgery or chemotherapy were included. The RT target volume was defined as the tumor bed or gross tumor with margin, and selective irradiation of the nodal area was performed when involved. The 5-year local recurrence-free survival rate was 94.7%. Overall, 53 recurrences were observed, of which distant metastasis was the most common. No isolated infield or marginal failures were observed. No infield nodal failure occurred among the patients who had initial node metastases and received RT including the nodal areas. A high local control rate was achieved with the addition of RT. A target volume confined to the tumor bed or gross tumor plus margin with the involved lymph node stations seems reasonable. Introduction: We aimed to identify the role of radiotherapy (RT) in the treatment of thymic carcinoma as well as the optimal RT target volume. Materials and Methods: This single-institution retrospective study included 116 patients diagnosed with thymic carcinoma between November 2006 and December 2021 who received multimodal treatment including RT with or without surgery or chemotherapy. Seventy-nine patients (68.1%) were treated with postoperative RT, 17 patients (14.7%) with preoperative RT, 11 patients (9.5%) with definitive RT, and nine patients (7.8%) with palliative RT. The target volume was defined as the tumor bed or gross tumor with margin, and selective irradiation of the regional nodal area was performed when involved. Results: With a median follow-up of 37.0 (range, 6.7–174.3) months, the 5-year overall survival (OS), progression-free survival, and local recurrence-free survival rates were 75.2%, 47.7% and 94.7%, respectively. The 5-year OS was 51.9% in patients with unresectable disease. Overall, 53 recurrences were observed, of which distant metastasis was the most common pattern of failure (n = 32, 60.4%) after RT. No isolated infield or marginal failures were observed. Thirty patients (25.8%) who had lymph node metastases at the initial diagnosis had regional nodal areas irradiated. There was no lymph node failure inside the RT field. A tumor dimension of ≥5.7 cm (hazard ratio [HR] 3.01; 95% confidence interval [CI] 1.25–7.26; p = 0.030) and postoperative RT (HR 0.20; 95% CI 0.08–0.52; p = 0.001) were independently associated with OS. Intensity-modulated-RT-treated patients developed less overall toxicity (p < 0.001) and esophagitis (p < 0.021) than three-dimensional-conformal-RT-treated patients. Conclusions: A high local control rate was achieved with RT in the primary tumor sites and involved lymph node area in the treatment of thymic carcinoma. A target volume confined to the tumor bed or gross tumor plus margin with the involved lymph node stations seems reasonable. The advanced RT techniques with intensity-modulated RT have led to reduced RT-related toxicity. [ABSTRACT FROM AUTHOR]

Validation of coronary artery calcium (CAC) scores as prognostic factors of acute coronary events (ACE) development in breast cancer patients are demanded. We investigated prognostic impact of CAC on ACE development with cardiac exposure to radiation. We evaluated breast cancer patients with (n = 511) or without (n = 600) adjuvant radiotherapy (RT) between 2005 and 2013. CAC Agatston scores were analyzed using a deep-learning-based algorithm. Individual mean heart dose (MHD) was calculated, and no RT was categorized as 0 Gy. The primary endpoint was the development of ACE following breast surgery. In the RT and no-RT cohorts, 11.2% and 3.7% exhibited CAC >0, respectively. Over a 9.3-year follow-up period, the 10-year ACE rate was 0.7%. In the multivariate analysis, the CAC score was a significant risk factor for ACE (CAC >0 vs CAC = 0, 10-year 6.2% vs 0.2%, P < 0.001). In the subgroup with CAC >0, the 10-year ACE rates were 0%, 3.7%, and 13.7% for patients receiving mean heart doses of 0 Gy, 0–3 Gy, and >3 Gy, respectively (P = 0.133). Although CAC score was not predictive for non-ACE heart disease risk (P > 0.05), the 10-year non-ACE heart disease rates were 1.7%, 5.7%, and 7.1% for patients with CAC = 0 receiving MHD of 0 Gy, 0–3 Gy, and >3 Gy, respectively (P < 0.001). The CAC score was a significant predictor of ACE in patients with breast cancer. Although further studies are required, CAC score screening on simulation CT in patients undergoing breast RT can help identify those with high risk for ACE on a per-patient basis. • CAC score was successfully validated as a strong predictive factor for ACEs. • MHD was identified as a significant factor in development of ACE and NAHD. • Best efforts should be made to keep the dose to cardiac structures as low as possible. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with gastric mucosa-associated lymphoid tissue lymphoma (GML), irradiation of the pancreas is inevitable owing to its anatomical proximity to the stomach. This is the first study to demonstrate the association between RT exposure and the risk of development of diabetes mellitus (DM) in patients with GML by measuring individual-based dose parameters of the pancreas. The findings of this study demonstrate the association between incidental pancreatic irradiation and DM. Obesity and sex were key risk factors for DM. Considering the risk of DM, the pancreas should no longer be neglected during RT planning, particularly in male patients and patients with obesity. The long-term effect of radiation on the pancreas in pediatric patients has been studied without individual radiation dosimetric data. This study investigated the effect of radiotherapy on the risk of developing diabetes mellitus (DM) in patients with gastric mucosa-associated lymphoid tissue lymphoma (GML), using individual radiation dosimetric analysis. Retrospective analysis reviewed the data of 225 patients without a history of DM receiving curative treatment for stage IE GML. Involved-site radiotherapy was delivered to the whole stomach in 83 patients. The pancreas was delineated in each patient's computed tomography scan for dosimetric analysis. At a median follow-up of 49.0 months, the 5-year cumulative incidence of DM was 4.5%, 9.6%, and 1.6% in all patients, patients who received radiotherapy, and patients who did not receive radiotherapy, respectively (p = 0.009). Mean pancreatic dose (Dmean; p = 0.009), sex (p = 0.043), and body mass index (BMI; p = 0.008) were independently associated with DM. Using recursive partitioning analysis, patients were classified into low, intermediate, and high-risk groups, with 5-year DM incidence rates of 0.0%, 3.1%, and 15.6%, respectively (p < 0.001). Incidental irradiation of the pancreas can increase the risk of DM, which may be stratified according to patient sex and BMI. [ABSTRACT FROM AUTHOR]

Simple Summary: With advances in radiotherapy (RT) technique and more frequent use of stereotactic ablative radiotherapy (SABR), precise segmentation of all brain metastases (BM) including a small volume of BM is essential to choose an appropriate treatment modality. However, the process of detecting and manually delineating BM with small volumes often results in missing delineation and requires a great amount of labor. To address this issue, we present a useful deep learning (DL) model for the detection and segmentation of BMwith contrast-enhanced magnetic resonance images. Specifically, we applied effective training techniques to detect and segment a BM of less than 0.04 cc, which is relatively small compared to previous studies. The results of our DL model demonstrated that the proposed methods provide considerable benefit for BM, even small-volume BM, detection, and segmentation for SABR. Recently, several efforts have been made to develop the deep learning (DL) algorithms for automatic detection and segmentation of brain metastases (BM). In this study, we developed an advanced DL model to BM detection and segmentation, especially for small-volume BM. From the institutional cancer registry, contrast-enhanced magnetic resonance images of 65 patients and 603 BM were collected to train and evaluate our DL model. Of the 65 patients, 12 patients with 58 BM were assigned to test-set for performance evaluation. Ground-truth for BM was assigned to one radiation oncologist to manually delineate BM and another one to cross-check. Unlike other previous studies, our study dealt with relatively small BM, so the area occupied by the BM in the high-resolution images were small. Our study applied training techniques such as the overlapping patch technique and 2.5-dimensional (2.5D) training to the well-known U-Net architecture to learn better in smaller BM. As a DL architecture, 2D U-Net was utilized by 2.5D training. For better efficacy and accuracy of a two-dimensional U-Net, we applied effective preprocessing include 2.5D overlapping patch technique. The sensitivity and average false positive rate were measured as detection performance, and their values were 97% and 1.25 per patient, respectively. The dice coefficient with dilation and 95% Hausdorff distance were measured as segmentation performance, and their values were 75% and 2.057 mm, respectively. Our DL model can detect and segment BM with small volume with good performance. Our model provides considerable benefit for clinicians with automatic detection and segmentation of BM for stereotactic ablative radiotherapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients with glioblastoma (GBM) involving the ventricles are at high risk of ventricle opening during surgery and potential ventricular tumor spread. We evaluated the effectiveness of whole-ventricular radiotherapy (WVRT) in reducing intraventricular seeding in patients with GBM and identified patients who could benefit from this approach. Methods and Materials: We retrospectively reviewed the data of 382 patients with GBM who underwent surgical resection and temozolomide-based chemoradiotherapy. Propensity score matching was performed to compensate for imbalances in characteristics between patients who did [WVRT (+); n=59] and did not [WVRT (–); n=323] receive WVRT. Local, outfield, intraventricular, and leptomeningeal failure rates were compared. Results: All patients in the WVRT (+) group had tumor ventricular involvement and ventricle opening during surgery. In the matched cohort, the WVRT (+) group exhibited a significantly lower 2-year intraventricular failure rate than the WVRT (–) group (2.1% vs. 11.8%; P=0.045), with no difference in other outcomes. Recursive partitioning analysis stratified the patients in the WVRT (–) group at higher intraventricular failure risk (2-year survival, 14.2%) due to tumor ventricular involvement, MGMT unmethylation, and ventricle opening. WVRT reduced the intraventricular failure rate only in high-risk patients (0% vs. 14.2%; P=0.054) or those with MGMT-unmethylated GBM in the matched cohort (0% vs. 17.3%; P=0.036). Conclusions: WVRT reduced the intraventricular failure rate in patients with tumor ventricular involvement and ventricle opening during surgery. The MGMT-methylation status may further stratify patients who could benefit from WVRT. Further prospective evaluation of WVRT in GBM is warranted. [ABSTRACT FROM AUTHOR]

Purpose: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx).Methods and Materials: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis.Results: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively.Conclusions: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable. [ABSTRACT FROM AUTHOR]

We evaluated prognostic factors of adult low-grade glioma (LGG) according to the new 2016 WHO classification. Records of 153 patients diagnosed with WHO grade II LGG between 2003 and 2015 were retrospectively reviewed. Based on the 2016 WHO classification, 80 patients (52.3%) had diffuse astrocytoma, IDH-mutant; 45 (29.4%) had oligodendroglioma, IDH-mutant and 1p/19q-codeleted (ODG); and 28 (18.3%) had diffuse astrocytoma, IDH-wildtype. Gross total resection (GTR) was performed in 71 patients (46.4%), subtotal resection in 31 (20.3%), partial resection in 43 (28.1%), and biopsy in 8 (5.2%). One hundred two patients (66.7%) received postoperative radiotherapy. The 5- and 10-year progression-free survival (PFS) rates were 72.7% and 51.5%, respectively, and the 5- and 10-year overall survival (OS) rates were 82.5% and 63.5%, respectively. GTR and IDH-mutant and/or 1p/19q codeletion were favorable prognostic factors for PFS and OS. Patients with IDH-wildtype had significantly decreased OS. Among patients with ODG who underwent GTR, no recurrence was observed after radiotherapy. Patients who underwent non-GTR frequently experienced recurrence after radiotherapy (IDH-mutant: 47.6%, IDH-wildtype: 57.9%). In conclusion, molecular classification of LGG was of prognostic relevance, with IDH-wildtype patients having a particularly poor outcome, regardless of the treatment. Favorable results were observed in patients who underwent GTR. [ABSTRACT FROM AUTHOR]

Background: Tomotherapy-based total body irradiation (TBI) is performed using the head-first position (HFP) and feet-first position (FFP) due to treatment length exceeding the 135 cm limit. To reduce the dosimetric variation at the match lines, we propose and verify a volumetric gradient matching technique (VGMT) by combining TomoHelical (TH) and TomoDirect (TD) modes.Methods: Two planning CT image sets were acquired with HFP and FFP using 15 × 55 × 18 cm3 of solid water phantom. Planning target volume (PTV) was divided into upper, lower, and gradient volumes. The junction comprised 2-cm thick five and seven gradient volumes (5-GVs and 7-GVs) to create a dose distribution with a gentle slope. TH-IMRT and TD-IMRT plans were generated with 5-GVs and 7-GVs. The setup error in the calculated dose was assessed by shifting dose distribution of the FFP plan by 5, 10, 15, and 20 mm in the longitudinal direction and comparing it with the original. Doses for 95% (D95) and 5% of the PTV (D5) were calculated for all simulated setup error plans. Absolute dose measurements were performed using an ionization chamber in the junction.Results: The TH&TD plan produced a linear gradient in junction volume, comparable to that of the TH&TH plan. D5 of the PTV was 110% of the prescribed dose when the FFP plan was shifted 0.7 cm and 1.2 cm in the superior direction for 5-GVs and 7-GVs. D95 of the PTV decreased to < 90% of the prescribed dose when the FF plan was shifted 1.1 cm and 1.3 cm in the inferior direction for 5-GVs and 7-GVs. The absolute measured dose showed a good correlation with the calculated dose in the gradient junction volume. The average percent difference (±SD) in all measured points was - 0.7 ± 1.6%, and the average dose variations between depths was - 0.18 ± 1.07%.Conclusion: VGMT can create a linear dose gradient across the junction area in both TH&TH and TH&TD and can minimize the dose sensitivity to longitudinal setup errors in tomotherapy-based TBI. [ABSTRACT FROM AUTHOR]

Intracranial germinoma sometimes present as bifocal germinoma, and whether bifocal germinoma should be treated as a synchronous or disseminated disease remains unclear. This study aimed to determine the optimal treatment modality for bifocal germinoma. Patients with bifocal germinoma who received radiotherapy (RT) from March 1990 to August 2017 were included for analysis. A total of 21 patients were included. The median follow-up period was 76.2 months (range, 6.2–305.4 months). There were 17 patients who received cranio-spinal irradiation (CSI) with local RT; 3, whole ventricular RT (WVRT) with local RT; and 1, local RT only. Three recurrences occurred (1 patient each among those who underwent CSI, WVRT, and local RT). Recurrence in the patient who received CSI and who received WVRT occurred in the right thalamus and right frontal convexity, respectively. Meanwhile, the patient who received local RT showed not only a recurred lesion in the hypothalamus, but also cerebrospinal fluid seeding. For this patient, salvage CSI was performed and complete response was achieved after treatment. However, after 9 years and 6 months, he was diagnosed with glioblastoma and expired. As for toxicity, although 17 patients showed decrease in complete blood count levels during treatment, all patients recovered soon after treatment completion. Our findings suggest that bifocal germinoma may be considered as a disseminated disease when considering the patterns of failure according to RT fields. In addition, patients who received CSI showed low acute toxicity rates. However, further studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Background and Purpose: Majority of patients with locoregionally recurrent rectal cancer will require re-irradation (reRT). This study aimed to analyze the treatment outcomes, particularly infield progression, and severe late toxicity rates after reRT for recurrent rectal cancer and further identify a subgroup of patients who may optimally benefit from reRT. Materials and Methods: Patients with rectal cancer who underwent reRT to the pelvis between January 2000 and December 2017 were included for analysis. Results: The records of 41 patients were retrospectively reviewed. The median follow-up period after reRT was 53.7 months (range 3.5–130.3 months). The 2-year infield progression-free rate (IPFR) was 49.4%. The 2-year overall survival (OS) and progression-free survival (PFS) rates were 55.3 and 28.5%, respectively. Severe late toxicity events occurred in 17 patients, and the median time from reRT to severe late toxicity event was 10.5 months (range 2.3–33.3 months). The 2-year severe late toxicity free-rate (SLTFR) was 55.5%, and the median SLTFR was 33.3 months. Patients who did not experience severe late toxicity events showed a significantly higher number of recurred tumors at the posterior or lateral location compared to axial or anterior location. The selected subgroup with recurrent tumor size <3.3 cm and treated with total reRT dose of >50 Gyab10 (n = 13) showed superior IPFR, OS, and PFS to the other patients. Conclusion: ReRT was a reasonable treatment option for patients with locoregionally recurrent rectal cancer. However, severe late toxicity rates were substantially high. Thus, patients indicated for ReRT with curative dose should be selected properly according to tumor size and location. [ABSTRACT FROM AUTHOR]

Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT. This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures. Median age was 44 years (range, 19–79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1–268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control (P = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P = 0.03) or stereotactic radiosurgery (P = 0.04). Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity. [ABSTRACT FROM AUTHOR]

Purpose: Spinal cord gliomas are rare, and there is no consensus on the optimal radiotherapy (RT) regimen. Herein, we investigated therapeutic outcomes in spinal cord gliomas to obtain clues for the optimal RT regimen.Methods: We assessed 45 patients who received RT for primary spinal cord non-ependymoma gliomas between 2005 and 2017: 37 (82%) received postoperative RT, 6 (13%) underwent definitive RT without surgery, and 2 (5%) received salvage RT for recurrent tumors. Craniospinal irradiation (CSI; median, 40 Gy) was administered in 4 patients with seeding at diagnosis; all other patients received local RT only (median, 50.4 Gy).Results: In all 23 failures occurred (20 in patients without initial seeding +3 in patients with initial seeding and CSI; median follow-up, 33 months). The 2‑year overall survival and progression-free survival rates were 74 and 54%, respectively. Overall, 13 (32%) new seeding events outside the local RT field developed either first or subsequently. Tumor grade was significantly associated with survival endpoints (p = 0.009, 0.028) and overall seeding rates (p = 0.042). In grade II tumors, seeding developed in 23%, with a dismal prognosis (median, 10 months after RT). In grade III tumors, seeding developed in 45% with diverse prognosis. In grade IV tumors, seeding developed in 45%. The survival of patients with newly developed seeding was significantly worse than the others (2-year 50%, p < 0.001).Conclusion: To encompass a considerable rate of progressive disease seeding, aggressive treatment such as pre-emptive application of CSI needs to be considered for high-grade spinal cord gliomas with adverse features. Prophylactic CSI could be an option for survival prolongation and requires prospective validation. [ABSTRACT FROM AUTHOR]

Purpose: Although locally invasive or recurrent fibromatosis is primarily treated with surgery, radiotherapy (RT) produces local control for recurrent/unresectable tumors or those with positive surgical margins. Herein, we describe our updated institutional experience with RT to treat fibromatosis. Methods: Forty-seven patients with fibromatosis received RT between 1990 and 2015, and were followed for ≥12 months. Eight patients received RT for gross tumors, and 39 received postoperative RT after single/multiple prior surgeries. A median dose of 54 Gy was prescribed for definitive RT; 48.6, 50.4, and 54 Gy were prescribed for R0, R1, and R2 resected tumors, respectively. Recurrences were classified as in-field, marginal, or out-field. Prognostic factors were also evaluated. Results: Seven recurrences were noted, including 2 in-field, 4 marginal, and 1 out-field, after a median follow-up of 60 months. In-field recurrences occurred in 1 patient who received 40.5 Gy of salvage RT after postoperative recurrence and another who received 45 Gy for R1 resection after multiple prior operations. All marginal failures were due to insufficient clinical target volume (CTV) margins regardless of dose (3 with 45 Gy and 1 with 54 Gy). On multivariate analysis, a CTV margin ≥5 cm and dose >45 Gy were significant predictors of non-recurrence (p = 0.039 and 0.049, respectively). Subgroup analysis showed that patients with both an CTV margin ≥5 cm and a dose >45 Gy showed a favorable outcome. Conclusions: RT is a valuable option for treating aggressive fibromatosis; doses ≥45 Gy and a large field produce optimal results. For in-field control, a higher dose is more necessary for gross residual tumors than for totally excised lesions. [ABSTRACT FROM AUTHOR]

Purpose/objective This study aimed to assess protocol compliance based on an individual case review (ICR) of the Korean Radiation Oncology Group-0806 trial. Methods and materials For the ICR, 747 participants were divided into eight subgroups based on internal mammary node irradiation (IMNI), tumor laterality, and surgery type. Next, 15% of patients were randomly selected within each subgroup, and corresponding hospitals were subsequently requested to upload information related to radiation therapy (RT) planning. We reviewed the dose distributions of targets and organs at risk to determine protocol compliance. Results Data of 102 patients were collected. Overall, RT plans were found to be mostly protocol-compliant, with acceptability rates of 60–80% despite deviations in the ipsilateral lung in Arm 2 (IMNI group). However, despite few deviations, a subgroup analysis revealed significant differences in protocol compliance. Among RT techniques, plans using standard and partial wide tangents were most compliant in both Arms. In this ICR, the estimated survival benefits based on IMN doses were 7.7%, 8.4%, and 7.2% for all, breast-conserving surgery, and mastectomy cases, respectively. Conclusion This ICR demonstrated overall protocol compliance, despite significant differences with regard to IMN irradiation and organs at risk according to subgroups and adopted field arrangements. [ABSTRACT FROM AUTHOR]

Background: Advanced-stage hepatocellular carcinoma (HCC) has an extremely poor prognosis although sorafenib, which is the treatment of choice, has provided survival benefits. Among advanced diseases, liver-confined HCC, which invades the vasculature without extrahepatic metastasis, requires novel therapeutic management beyond using sorafenib alone. Currently, the Korean Liver Cancer Study Group and National Comprehensive Cancer Network guidelines recommend combined radiotherapy (RT) and chemotherapy for some selected cases. For advanced liver-confined HCC, focal liver irradiation, RT technological development, and optimal selection of RT-suitable patients enable clinicians to use RT-involving multimodality treatments based on oncologic principles, such as concurrent chemoradiotherapy, which represent effective multimodality treatments for several types of malignancy. Summary: In this review, we discuss the need to develop novel therapeutic approaches for liver-confined HCC and clinical applications of RT-involving multimodality treatments for advanced liver-confined HCC. Conclusion: RT-involving multimodality treatments can enhance the overall therapeutic successes for advanced liver-confined HCC and also provide potential cures to some patients via conversion to a resectable condition. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Although there have been many attempts to increase the therapeutic ratio of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma (MALToma), only a few planning studies have reported the efficacy of the modern radiotherapy technique till date. Therefore, we performed the dosimetric comparison among 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) plans, using deep-inspiration breath hold (DIBH) or free-breathing (FB) techniques, to determine the most optimal plan for gastric MALToma.Methods: We evaluated 9 patients with gastric MALToma for whom 3D-CRT, step-and-shoot IMRT (SIMRT), volumetric-modulated arc therapy (VMAT), and tomotherapy plans with identical prescribed doses were generated using DIBH or FB computed tomography (CT). Planning target volume (PTV) coverage and non-target doses were calculated for each plan and compared with plan quality metric (PQM) scores.Results: All 72 plans of 9 patients satisfied our dosimetric goals, and the IMRT plans and 3D-CRT plans had similarly good conformity index values with no differences related to respiratory movement. IMRT plans yielded significantly better doses to the organs-at-risk, and DIBH plans yielded significantly lower liver, heart, and lung Dmean and spinal cord Dmax with smaller irradiated volumes compared to FB plans. For the mean PQM scores, VMAT-DIBH and SIMRT-DIBH yielded the best scores, whereas 3D plans provided reduced beam monitor unit values.Conclusion: Our findings demonstrate that modern RT technologies (DIBH with VMAT or SIMRT) could potentially provide excellent target coverage for gastric MALToma while reducing doses to organs-at-risk. However, the relevance of the most optimal plan considering clinical outcomes should be confirmed further in a larger patient cohort. [ABSTRACT FROM AUTHOR]

Background: Despite detailed instruction for full bladder, patients are unable to maintain consistent bladder filling during a 5-week pelvic radiation therapy (RT) course. We investigated the best bladder volume estimation procedure for verifying consistent bladder volume.Methods: We reviewed 462 patients who underwent pelvic RT. Biofeedback using a bladder scanner was conducted before simulation and during treatment. Exact bladder volume was calculated by bladder inner wall contour based on CT images (Vctsim). Bladder volume was estimated either by bladder scanner (Vscan) or anatomical features from the presacral promontory to the bladder base and dome in the sagittal plane of CT (Vratio). The feasibility of Vratio was validated using daily megavoltage or kV cone-beam CT before treatment.Results: Mean Vctsim was 335.6 ± 147.5 cc. Despite a positive correlation between Vctsim and Vscan (R2 = 0.278) and between Vctsim and Vratio (R2 = 0.424), Vratio yielded more consistent results than Vscan, with a mean percentage error of 26.3 (SD 19.6, p < 0.001). The correlation between Vratio and Vctsim was stronger than that between Vscan and Vctsim (Z-score: - 7.782, p < 0.001). An accuracy of Vratio was consistent in megavoltage or kV cone-beam CT during treatment. In a representative case, we can dichotomize for clinical scenarios with or without bowel displacement, using a ratio of 0.8 resulting in significant changes in bowel volume exposed to low radiation doses.Conclusions: Bladder volume estimation using personalized anatomical features based on pre-treatment verification CT images was useful and more accurate than physician-dependent bladder scanners.Trial Registration: Retrospectively registered. [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]

• Integrating various input features for predictive models of AF after NSCLC RT. • Machine learning- and deep learning-based predictive models for AF were developed. • Performance of the predictive models was well preserved in external validation. • Our findings identified maximum doses to the heart and SAN as key features of AF. Radiotherapy (RT) in non-small cell lung cancer (NSCLC) can induce cardiac adverse events, including atrial fibrillation (AF), despite advanced RT. This study integrates patient-specific information to develop learning-based models to predict the incidence of AF following NSCLC chemoradiotherapy (CRT) and evaluates these models using institutional and external datasets. Institutional and external patient cohorts consisted of 321 and 187 NSCLC datasets who received definitive CRT, including 17 and 6 AF incidences, respectively. The network input had 159 features with clinical, dosimetry, and diagnostic. The class imbalance was mitigated by synthetic minority oversampling technique. To handle various types of input features, machine learning-based model adopted an intervention technique that chose one feature with the largest weight at each dosimetry sub-group in feature selection process, while deep learning-based model employed a hybrid architecture assigning different types of networks to corresponding input paths. Performance was assessed by area under the curve (AUC). The key features were investigated for the machine and deep learning-based models. The hybrid deep learning model outperformed the machine learning-based algorithm in internal validation (AUC: 0.817 vs. 0.801) and produced more consistent performance in external validation (AUC: 0.806 vs. 0.776). Importantly, maximum dose to heart and sinoatrial node (SAN) were found to be the key features for both learning-based models in external and internal validations. The learning-based predictive models showed consistent prediction performance across internal and external cohorts, identifying maximum heart and SAN dose as key features for the incidence of AF. [ABSTRACT FROM AUTHOR]

• Radiotherapy improved survival in adult grade II–III intracranial ependymomas. • Radiotherapy also improved outcomes for adult grade II intracranial ependymomas. • International collaborative efforts to pool these rare patients are urgently warranted. To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II–III intracranial ependymoma (IEPN). A total of 172 pathologically confirmed adult grade II–III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis. The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P = 0.002), PFS (P = 0.002), and OS (P = 0.043). Older age (P < 0.001), WHO grade III (P < 0.001), larger tumor size (P = 0.004), and lesser surgical extent (P < 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P = 0.010), PFS (P = 0.007), and OS (P = 0.069) on multivariate analysis for grade II IEPNs. This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II–III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted. [ABSTRACT FROM AUTHOR]

Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8–59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m2) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4–43.9) for the entire cohort, and 22.5 months (range, 12.0–43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity (≥Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity. [ABSTRACT FROM AUTHOR]

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]