Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-ß (Aß) plaques and neurofibrillary tangles in the brain. During the progression of AD, microglia can be polarized from anti-inflammatory M2 to pro-inflammatory M1 phenotype. The activation of triggering receptor expressed on myeloid cells 2 (TREM2) may result in microglia phenotype switching from M1 to M2, which finally attenuated Aß deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate Aß pathology and cognitive deficits in AD; however, the therapeutic mechanisms of LDIR against AD-related pathology have been little studied. First, we reconfirm that LDIR (two Gy per fraction for five times)-treated six-month 5XFAD mice exhibited (1) the reduction of Aß deposition, as reflected by thioflavins S staining, and (2) the improvement of cognitive deficits, as revealed by Morris water maze test, compared to sham-exposed 5XFAD mice. To elucidate the mechanisms of LDIR-induced inhibition of Aß accumulation and memory loss in AD, we examined whether LDIR regulates the microglial phenotype through the examination of levels of M1 and M2 cytokines in 5XFAD mice. In addition, we investigated the direct effects of LDIR on lipopolysaccharide (LPS)-induced production and secretion of M1/M2 cytokines in the BV-2 microglial cells. In the LPS- and LDIR-treated BV-2 cells, the M2 phenotypic marker CD206 was significantly increased, compared with LPS- and sham-treated BV-2 cells. Finally, the effect of LDIR on M2 polarization was confirmed by detection of increased expression of TREM2 in LPS-induced BV2 cells. These results suggest that LDIR directly induced phenotype switching from M1 to M2 in the brain with AD. Taken together, our results indicated that LDIR modulates LPS- and Aß-induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as Aß deposition and memory loss.

Serum lactate dehydrogenase levels at presentation in stage IV non-small cell lung cancer: predictive value of metastases and relation to survival outcomes.

This study aimed to evaluate the clinical correlations between serum lactate dehydrogenase (LDH) levels and tumor characteristics and to investigate the prognostic impact of serum LDH levels in advanced non-small cell lung cancer (NSCLC). A total of 394 patients were included in the present study between June 2007 and January 2013. All eligible patients had serum LDH levels available before treatment, and whole-body metastatic extent was measured using whole-body metastatic scores, as determined by 18(F)-fludeoxyglucose positron emission tomography scans from 1 to 7 as the sum of each metastatic region. The diagnostic cutoff value for an abnormal serum LDH level was 450 IU/L. The median serum LDH level was 477 IU/L (range, 113-2850), and 224 (56.9 %) patients had abnormal serum LDH levels. The serum LDH levels showed no significant associations with age, gender, histology, tumor differentiation, and smoking history. However, the proportion of patients with abnormal serum LDH levels was statistically significantly higher in the high total metastatic score group (scores 3-7) than in the low total metastatic score group (scores 1-2) (65.3 vs 50.4 %, p = 0.001). In a multivariate survival analysis, age (p = 0.001), gender (p = 0.001), histology (p = 0.003), tumor differentiation (p = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.001), LDH levels (p = 0.046), and treatment factors (p = 0.001) proved to be independent prognostic factors for survival outcomes. The results of this study suggest that the serum LDH levels at presentation may be significantly correlated with whole-body tumor extent and might independently but modestly prognosticate OS in stage IV NSCLC.

Can serum dynamics of carcinoembryonic antigen level during neoadjuvant chemoradiotherapy in rectal cancer predict tumor response and recurrence? A multi-institutional retrospective study.

PURPOSE: We evaluate whether the change of carcinoembryonic antigen (CEA) level before and after preoperative chemoradiotherapy (CRT) in rectal cancer affects tumor response and recurrence or not. METHODS: We retrospectively analyzed 1447 rectal cancer patients who underwent preoperative CRT followed by curative surgery. All patients received preoperative radiotherapy of 50.4 Gy in 28 fractions with 5-fluorouracil or capecitabine. Total mesorectal excision was performed 4 to 8 weeks after preoperative CRT. CEA levels were checked before and after CRT. Clinical and pathologic factors were analyzed for tumor response and recurrence. RESULTS: Post-CRT CEA level (cutoff value, 2.5 ng/mL) was not a significant factor for tumor response on the multivariate analysis (p = 0.095). Patients were categorized according to the pre- and post-CRT CEA level (group A: pre-CRT CEA ≤5 ng/mL; group B: pre-CRT CEA >5 ng/mL and post-CRT CEA ≤2.5 ng/mL; group C: pre-CRT CEA >5 ng/mL and post-CRT CEA >2.5 ng/mL). The relapse-free survival (RFS) at 5 years was significantly higher in group A than in groups B and C (82.6 vs. 73.7 % vs. 72.2 %, p < 0.001). The overall survival (OS) at 5 years was significantly higher in group A than in groups B and C (90.1 vs. 84.4 % vs. 83.4 %, p < 0.001). However, there is no significant difference for RFS and OS between groups B and C (all, p > 0.05). CONCLUSIONS: Decline of elevated CEA level (>5 ng/mL) during preoperative chemoradiotherapy has no significant effect on tumor response and recurrence in rectal cancer.

Safety of hypofractionated volumetric modulated arc therapy for early breast cancer: A preliminary report.

The present study attempts to evaluate the acute and subacute toxicities of hypofractionated volumetric modulated arc therapy (HFX-VMAT) in patients with early breast cancer (EBC). It is a retrospective analysis of 23 patients treated with HFX-VMAT after breast-conserving surgery between September 2021 and February 2022. A total dose of 50.05 to 52.55 Gy was delivered, consisting of 40.05 Gy to the ipsilateral whole breast in 15 fractions of 2.67 Gy and a tumor bed boost dose of 10-12.5 Gy in 4-5 fractions. The primary endpoint was acute/subacute radiation pneumonitis (RP). The secondary endpoint was poor cosmesis, indicating acute/subacute radiation dermatitis. Chest computed tomography (CT) and the Common Terminology Criteria for Adverse Events v.5.0 were used to assess acute and subacute RP and dermatitis, respectively, during radiotherapy (RT) and at 3- and 6-months post-RT. The median follow-up duration was 3.8 months (range, 2.3-4.2). A total of seven patients developed RP. None of these patients presented RP-related symptoms; the diagnosis was based on radiologic findings observed on follow-up chest CT. Among the seven patients with RP, five had right-sided, and two had left-sided breast tumors (71.4 vs. 28.6%; P=0.026). Grade 1 erythema was observed in 19 patients (82.6%) and grade 2 erythema in four (17.4%). The mean target dose, D105% (the dose received by 105% of the target volume), homogeneity index, mean lung dose, ipsilateral lung V20 (the percentage volume receiving 20 Gy), and V30 (the percentage volume receiving 30 Gy) for ipsilateral whole breast RT were significantly associated with RP (P=0.039, 0.047, 0.018, 0.015, 0.018 and 0.003, respectively.). HFX-VMAT showed tolerable acute/subacute toxicities. Therefore, HFX-VMAT is an effective and safe treatment option for EBC.

Clinicopathological Outcomes in Patients With Locally Advanced Rectal Cancer Undergoing Preoperative Short-Versus Long-course Chemoradiotherapy With Delayed Surgery.

BACKGROUND/AIM: We aimed to compare the clinicopathological outcomes in patients with locally advanced rectal cancer after short- or long-course concurrent chemoradiotherapy (CCRT) followed by delayed surgery. PATIENTS AND METHODS: The records of 94 patients with cT3-4N0-2M0 rectal cancer who received CCRT between 2010 and 2017 were reviewed. Short-course radiotherapy (RT) was delivered with a median total dose of 25 Gy in five fractions (n=27), and long-course RT was delivered with a median total dose of 50.4 Gy in 28 fractions (n=67). The following concurrent chemotherapy regimens were administered: 5-fluorouracil plus leucovorin in 58 and capecitabine in 24; in 12 cases agents were unknown. The median interval between CCRT and surgery was 8 weeks. Adjuvant chemotherapy was administered after surgery in 80 patients (5-fluorouracil plus leucovorin, n=54; capecitabine, n=9; other, n=14; and unknown, n=3). Propensity-score matching analysis was conducted. RESULTS: The median follow-up duration was 4.3 years. There were no statistically significant differences between the short- and long-course RT groups in sphincter preservation (85.2% vs. 92.5%, p=0.478), pathological complete remission (18.5% vs. 14.9%, p=0.905), downstaging (44.4% vs. 26.9%, p=0.159), and negative circumferential resection margin (92.6% vs. 89.6%, p=0.947) rates. No differences were found in survival outcomes between the short- and long-course groups at 3 years (overall survival: 91.8% vs. 88.1%, p=0.790; disease-free survival, 75.2% vs. 72.5%, p=0.420; locoregional relapse-free survival, 90.5% vs. 98.4%, p=0.180; and distant metastasis-free survival, 79.6% vs. 73.5%, p=0.490). Similar results were observed after PSM. CONCLUSION: Clinically, short-course CCRT may be a feasible alternative to long-course CCRT in patients with locally advanced rectal cancer.

Prostate only radiotherapy using external beam radiotherapy: A clinician's perspective.

Prostate-only radiotherapy (PORT) is widely used as the definitive treatment for localized prostate cancer. Prostate cancer has an α/ß ratio; therefore, radiotherapy (RT) with a large fraction size is biologically effective for tumor control. The current external beam RT technique for PORT has been improved from three-dimensional conformal RT to intensity-modulated, stereotactic body, and image-guided RTs. These methods are associated with reduced radiation exposure to normal tissues, decreasing urinary and bowel toxicity. Several trials have shown improved local control with dose escalation through the aforementioned methods, and the efficacy and safety of intensity-modulated and stereotactic body RTs have been proven. However, the management of RT in patients with prostate cancer has not been fully elucidated. As a clinician, there are several concerns regarding the RT volume and dose considering the patient's age and comorbidities. Therefore, this review aimed to discuss the radiobiological basis and external beam technical advancements in PORT for localized prostate cancer from a clinician's perspective.

The prognostic value of PET/CT evaluation with Deauville score on the recurrence and survival in diffuse large B-cell lymphoma: a multi-institutional study of KROG 17-02.

The Korean Radiation Oncology Group (KROG) assessed the value of Deauville score (DS) on 18F-fluorodeoxyglucose Positron emission tomography-computed tomography (FDG PET/CT) as a predictor of recurrence and survival after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in diffuse large B-cell lymphoma (DLBCL). A total of 512 patients with stage I-III DLBCL who received six cycles of R-CHOP with or without radiation therapy (RT) and obtained treatment responses according to PET-CT imagings after R-CHOP ± RT were included. Patients were sorted into two arms; DS 4-5 arm (n = 24) was matched at a 1:2 ratio with DS 1-3 arm (n = 48) using propensity score matching method. After a median follow-up time of 37.2 months, the recurrence-free survival rate (86.6% vs. 66.8%, P = 0.041) and overall survival rate (86.9% vs. 62.2%, P = 0.009) at 5 years were significantly different between the DS 1-3 and DS 4-5 arms. DS 4-5 arm showed higher 5-years locoregional recurrence-free survival (88.8% vs. 74.3%, P = 0.155) and distant failure-free survival (91.1% vs. 84.3%, P = 0.333) than DS 1-3 arm. In the multivariate analysis, DS was still a significant factor for recurrence-free survival [hazard ratio (HR), 3.840 and confidence interval (CI), 1.068-13.806; P = 0.039] and overall survival rates (HR 4.453 and CI 1.274-15.562; P = 0.019). This study showed and validated that Deauville score of 4-5 of PET-CT imaging taken after full-course of R-CHOP chemotherapy with or without RT could predict recurrence-free survival and overall survival in DLBCL patients.

Diabetes mellitus is a predictive factor for radiation pneumonitis after thoracic radiotherapy in patients with lung cancer.

PURPOSE: We evaluated the effects of diabetes mellitus (DM) and DM-related serologic factors (HbA1c and fasting glucose) on the development of radiation pneumonitis in patients with lung cancer. METHODS: We retrospectively analyzed the clinical data of 123 patients with lung cancer treated with radiotherapy. Radiation pneumonitis was scored according to the toxicity criteria of the Radiation Therapy Oncology Group. We used binary logistic regression analysis to find significant predictive factors for the development of grade ≥3 radiation pneumonitis. RESULTS: On univariable analysis, V20, mean lung dose, DM, HbA1c, and fasting glucose level were significantly associated with the development of grade ≥3 radiation pneumonitis. On multivariable analysis, V20, mean lung dose, DM, HbA1c, and fasting glucose level remained significant predictive factors for grade ≥3 radiation pneumonitis. The incidence of grade ≥3 radiation pneumonitis was 44.4% in patients with DM and 20.7% in patients without DM. The incidence of grade ≥3 radiation pneumonitis was 12.7% for HbA1c level ≤6.15% and 41.5% for HbA1c level >6.15%. The incidence of grade ≥3 radiation pneumonitis was 17.2% for fasting glucose level ≤121 mg/dL and 35.5% for fasting glucose level >121 mg/dL. CONCLUSION: DM, HbA1c, and fasting glucose level are significant predictive factors for the development of grade ≥3 radiation pneumonitis in patients with lung cancer. Patients with DM, patients who have HbA1c >6.15%, and patients who have fasting glucose >121 mg/dL should be treated with greater caution.

A multi-institutional and case-matched control study on treatment outcomes of consolidative radiotherapy after a full course of R-CHOP compared with R-CHOP alone in Stage I-II diffuse large B-cell lymphoma (KROG 17-02).

We compared treatment outcomes between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy alone with R-CHOP followed by consolidative radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL). We analyzed 404 patients with Stage I-II DLBCL who received six to eight cycles of R-CHOP and achieved a good response after a full course of chemotherapy. Propensity-score matching was used to assess the role of consolidative RT. The R-CHOP alone group (n = 184) was matched in a 1:2 ratio with the R-CHOP plus RT group (n = 92). Twenty-four (13.0%) of 184 patients receiving R-CHOP alone and 8 (8.7%) of 92 patients receiving R-CHOP plus RT had bulky diseases (>7.5 cm). A Deauville score of 1-2 was achieved for 159 (86.4%) of 184 patients receiving R-CHOP alone and 84 (91.3%) of 92 patients receiving R-CHOP plus RT. After a median follow-up time of 42 months, the recurrence-free survival (RFS) rate (86.7% vs 93.0%, P = 0.464) and overall survival rate (88.3% vs 95.1%, P = 0.295) at 5 years did not differ significantly between the R-CHOP alone and R-CHOP plus RT arms. In the additional multivariate analyses, large tumor size (>7.5 cm) was significantly associated with decreased RFS (hazard ratio, 2.368 and confidence interval, 1.837-6.697; P = 0.048). Consolidative radiation was not a significant factor for RFS (P = 0.563). Tumor size was a significant factor for RFS in the rituximab era. The outcome of omitting consolidative RT for good responders after six to eight cycles of R-CHOP chemotherapy was acceptable in early-stage DLBCL without a bulky disease.

Adjuvant Chemotherapy in Rectal Cancer Patients Treated With Preoperative Chemoradiation and Total Mesorectal Excision: A Multicenter and Retrospective Propensity-Score Matching Study.

PURPOSE: The role of adjuvant chemotherapy after preoperative chemoradiation therapy (CRT) and curative surgery in rectal cancer has yet to be definitely determined. We performed a retrospective and multicenter study to evaluate whether adjuvant chemotherapy (AC) could reduce recurrence and improve survival in locally advanced rectal cancer. METHODS AND MATERIALS: We analyzed data from 8 tertiary institutions for 1442 patients with rectal cancer who underwent preoperative CRT and total mesorectal excision. Patients were classified into 2 groups: the AC group (patients who received chemotherapy after surgery) and the observation group (those who did not receive chemotherapy after surgery). Propensity-score matching was used to assess the exact role of AC. The AC group was then subdivided to investigate the impact of adding oxaliplatin to 5-fluorouracil (5-FU). Group 1 was treated with 5-FU/folinic acid or capecitabine without oxaliplatin, and group 2 received 5-FU/folinic acid or capecitabine with oxaliplatin. RESULTS: The 3-year relapse-free survival rates in the AC and observation groups were 85.9% and 84.3%, respectively (P = .532). The 3-year overall survival rates in the AC and observation groups were 94.9% and 89.9%, respectively (P = .123). The rates of locoregional recurrence (2.2% vs 3.2%, P = .294) and distant metastasis (12.4% vs 12.9%, P = .927) at 3 years were not significantly different between the two groups. The 3-year relapse-free survival rates of group 1 and group 2 were 71.5% and 74.8%, respectively (P = .426). The 3-year overall survival rates of group 1 and group 2 were 89.9% and 96.5%, respectively (P = .102). CONCLUSIONS: This multicenter study found insufficient evidence to support the use of 5-FU-based AC after preoperative CRT and curative surgery in rectal cancer.

Preoperative short- vs. long-course chemoradiotherapy with delayed surgery for locally advanced rectal cancer.

PURPOSE: To compare the clinical outcomes between short-course chemoradiotherapy (CRT) and long-course CRT with delayed surgery in locally advanced rectal cancer patients. RESULTS: From 2010 to 2015, 19 patients were treated with short-course CRT and 53 patients were treated with LCRT. The sphincter-saving rate (89.5% vs. 94.3%, short-course CRT vs. long-course CRT), pathologic complete remission (21.1% vs. 13.2%), downstaging (47.4% vs. 26.4%), and treatment complications including anastomotic site leakage, bowel adhesion, and hematologic toxicity associated with short-course CRT were not significantly different from those associated with long-course CRT. 2-year overall survival was 90.0% and 91.2% (p = 0.448), respectively. METHODS AND MATERIALS: 72 patients with stage cT3-4N0-2M0 rectal cancer participated in a multicenter study. Short-course CRT treatment was as follows: a total of 25 Gy of radiotherapy was delivered in 5 equal doses with intensity modulated radiation therapy. Chemotherapy was consisted of Leucovorin 400 mg/m2 administered by bolus injection on day 1 and 5-Fluouracil 1200 mg/m2 given by continuous infusion on days 1 and 2. An additional three cycles of chemotherapy were administered before the surgery. Long-course CRT treatment was as follows: a total of 50.4 Gy of radiotherapy was delivered in 28 equal doses. Chemotherapy consisted of a bolus injection of 5-Fluouracil + Leucovorin during the first and last week of radiotherapy. Surgery was performed 6-8 weeks after completion of radiotherapy in both groups. CONCLUSIONS: Preoperative short-course CRT is an effective and safe modality. It is clinically comparable to long-course CRT in locally advanced rectal cancer.

Simple Prediction Model of Axillary Lymph Node Positivity After Analyzing Molecular and Clinical Factors in Early Breast Cancer.

The aim of this study was to evaluate the association between pretreatment molecular and clinical factors and axillary lymph node metastases in early breast cancer. A total of 367 consecutive breast cancer patients with cT1-2NxM0 who underwent breast conserving surgery and axillary lymph node dissection followed by whole breast irradiation were enrolled. We evaluated the pathologic tumor and node status, tumor differentiation, calcification, and lymphovascular invasion, the status of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 (EGFR1), and human epidermal growth factor receptor 2 (HER2), the expression of E-cadherin, P53, and Ki-67 index. Totally, 108 (29.4%) of the 367 patients had positive axillary lymph nodes. An increased tumor size (P = 0.024), the presence of lymphovascular invasion (P < 0.001), and Ki-67 index of >20% (P = 0.038) were significantly associated with axillary lymph node metastases on the multivariate analysis. In our study, 86.2% of the patients with all the unfavorable factors had an involvement of axillary nodal metastases, and only 12.2% of the patients with all the favorable predictors had positive axillary nodes. The predictive power was significant on the receiver operating curve (P < 0.001). We found that several factors, such as tumor size, lymphovascular invasion, and the Ki-67 index, are independent factors that predict positive ALNM on multivariate analysis for the patients with cT1-2 breast cancer. Clinicians simply could predict the probability of ALNM after verifying the molecular and clinical factors in early breast cancer.

Predictors of Distant Metastasis after Radical Surgery Followed by Postoperative Radiotherapy with or without Chemotherapy for Oropharyngeal Cancer.

PURPOSE: We investigated the prognostic factors for distant metastasis (DM) in patients with locally advanced oropharyngeal cancer (OPC) treated with surgery and adjuvant radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Eighty-five patients treated between January 1995 and August 2014 were evaluated retrospectively. Data regarding the pathological tumour and nodal status, human papillomavirus (HPV) status, treatment characteristics, and pretreatment maximum standardized uptake value (SUVmax) of 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography scan (18F-FDG PET-CT) were evaluated, and their influence on DM and survival outcomes were analyzed. RESULTS: Median follow-up period was 48.0 months. Recurrence was observed in 20 patients, including locoregional recurrence and DM. DM was observed in 13 patients. A multivariate analysis confirmed that the presence of lymphovascular invasion (p=0.031), lower neck lymph node (LN) involvement (p=0.006), SUVmax ≥ 9.7 (p=0.014), and tumour size ≥ 3 cm (p=0.037) significantly affected DM. HPV status was not associated with DM. Perineural invasion (p=0.048), lower neck LNinvolvement (p=0.008), SUVmax ≥ 9.7 (p=0.019), and tumour size ≥ 3 cm (p=0.033) were also significant factors for the DM-free survival rate. CONCLUSION: Lower neck LN involvement, high SUVmax in pretreatment 18F-FDG PET-CT, and large tumour size were predictive factors for DM in patients of OPC.

Analysis of Geometric Shifts and Proper Setup-Margin in Prostate Cancer Patients Treated With Pelvic Intensity-Modulated Radiotherapy Using Endorectal Ballooning and Daily Enema for Prostate Immobilization.

We evaluate geometric shifts of daily setup for evaluating the appropriateness of treatment and determining proper margins for the planning target volume (PTV) in prostate cancer patients.We analyzed 1200 sets of pretreatment megavoltage-CT scans that were acquired from 40 patients with intermediate to high-risk prostate cancer. They received whole pelvic intensity-modulated radiotherapy (IMRT). They underwent daily endorectal ballooning and enema to limit intrapelvic organ movement. The mean and standard deviation (SD) of daily translational shifts in right-to-left (X), anterior-to-posterior (Y), and superior-to-inferior (Z) were evaluated for systemic and random error.The mean ±â€ŠSD of systemic error (Σ) in X, Y, Z, and roll was 2.21 ±â€Š3.42 mm, -0.67 ±â€Š2.27 mm, 1.05 ±â€Š2.87 mm, and -0.43 ±â€Š0.89°, respectively. The mean ±â€ŠSD of random error (δ) was 1.95 ±â€Š1.60 mm in X, 1.02 ±â€Š0.50 mm in Y, 1.01 ±â€Š0.48 mm in Z, and 0.37 ±â€Š0.15° in roll. The calculated proper PTV margins that cover >95% of the target on average were 8.20 (X), 5.25 (Y), and 6.45 (Z) mm. Mean systemic geometrical shifts of IMRT were not statistically different in all transitional and three-dimensional shifts from early to late weeks. There was no grade 3 or higher gastrointestinal or genitourianry toxicity.The whole pelvic IMRT technique is a feasible and effective modality that limits intrapelvic organ motion and reduces setup uncertainties. Proper margins for the PTV can be determined by using geometric shifts data.

Soft Tissue Necrosis in Head and Neck Cancer Patients After Transoral Robotic Surgery or Wide Excision With Primary Closure Followed by Radiation Therapy.

Risk factors were evaluated for surgical bed soft tissue necrosis (STN) in head and neck cancer patients treated with postoperative radiation therapy (PORT) after transoral robotic surgery (TORS) or wide excision with primary closure. Sixty-seven patients were evaluated. STN was defined as ulceration and necrosis of the surgical bed or persistently unhealed high-grade acute mucositis with pain after PORT. The median RT dose of primary site was 63.6 Gy (range, 45-67.15 Gy) with 2 Gy/fx (range 1.8-2.2 Gy/fx). Total 41 patients (61.2%) were treated with concurrent chemoradiotherapy. The median follow-up period was 26 months. STN was diagnosed in 13 patients (19.4%). Most of the patients were treated with oral steroids, antibiotics, and analgesics and the lesions were eventually improved (median of 6 months after PORT). STN did not influence local control. A depth of invasion (DOI > 1.4 cm, odds ratio [OR] 14.04, p = 0.004) and maximum dose/fraction (CTVpmax/fx > 2.3 Gy, OR 6.344, p = 0.043) and grade 3 acute mucositis (OR 6.090, p = 0.054) were related to STN. The 12 (23.5%) of 51 oropharyngeal cancer patients presented STN, and the risk factors were DOI > 1.2 cm (OR 21.499, P = 0.005), CTVpmax/fx > 2.3 Gy (OR 12.972, P = 0.021) and grade 3 acute mucositis (OR 10.537, P = 0.052). Patients treated with TORS or WE with primary closure followed by PORT had a high risk of surgical bed STN. STN risk factors included DOI (>1.2-1.4 cm) and CTVpmax/fx (>2.3 Gy). Radiation therapy after TORS must be carefully designed to prevent STN.

A Dosimetric Comparative Analysis of TomoDirect and Three-Dimensional Conformal Radiotherapy in Early Breast Cancer.

PURPOSE: The purpose of this study is to compare dosimetric parameters of intensity-modulated mode of TomoDirect and three-dimensional conformal radiotherapy (3D-CRT) in patients with early breast cancer. METHODS: TomoDirect and 3D-CRT planning were carried out for 26 patients with early breast cancer who had received breast-conserving surgery. A total of 50.4 Gy in 28 fractions were prescribed to the planning target volume. The organs at risk (OAR) such as lung and heart were contoured. Planning target volume (PTV) dose coverage, radiation conformity index (RCI), radical dose homogeneity index (rDHI), and irradiation dose of organs at risk were compared between TomoDirect and 3D-CRT planning. RESULTS: The mean PTV dose (51.65±0.37 Gy) and V47.8 (100%) in TomoDirect were significantly higher than the mean PTV dose (50.88±0.65 Gy) and V47.8 (89.23%±0.06%) in 3D-CRT (all, p<0.001). The RCI value in TomoDirect was significantly better than that in 3D-CRT (1.00 vs. 1.13, p<0.001). However, the rDHI value in TomoDirect was not significantly better than that in 3D-CRT (0.72 vs. 0.67, p=0.056). The mean lung dose and V10, V20, V30, and V40 values of ipsilateral lung in TomoDirect were significantly lower than those in 3D-CRT (all, p<0.05). There is no significant difference in the V10, V20, V30, and V40 values of heart between TomoDirect and 3D-CRT. And the mean dose for heart in TomoDirect was marginally lower than that in 3D-CRT (1.05 Gy vs. 1.62 Gy, p=0.085). The mean dose for left anterior descending coronary artery in left breast cancer was significantly lower in TomoDirect than in 3D-CRT (7.2 Gy vs. 12.1 Gy, p<0.001). CONCLUSION: Compared to 3D-CRT, TomoDirect could result in favorable target coverage while reducing the irradiation dose of the ipsilateral lung for patients with early breast cancer.

Postoperative Radiotherapy Alone Versus Chemoradiotherapy in Stage I-II Endometrial Carcinoma: An Investigational and Propensity Score Matching Analysis.

PURPOSE: The purpose of this study was to compare the results of postoperative adjuvant radiotherapy (RT) and concurrent chemoradiotherapy (CRT) in stage I-II endometrial carcinoma. MATERIALS AND METHODS: We analyzed a total of 64 patients with surgically staged I-II endometrial carcinoma who were treated with postoperative adjuvant RT or concurrent CRT between March 1999 and July 2013. Thirty-two patients who received postoperative RT alone were matched with those who received postoperative CRT (n=32) in accordance to age, stage, and tumor histology. Overall survival and relapse-free survival, as well as toxicity of the RT and CRT arms were evaluated and compared. RESULTS: The 5-year overall survival rate was 90.0% for the RT arm and 91.6% for the CRT arm. There was no significant difference in overall survival between the two treatment arms (p=0.798). The 5-year relapse-free survival rate was 87.2% in the RT arm and 88.0% in the CRT arm. Again, no significant difference in relapse-free survival was seen between the two arms (p=0.913). In a multivariate analysis, tumor histology was an independent prognostic factor for relapse-free survival (hazard ratio, 3.67; 95% of CI, 2.34 to 7.65; p=0.045). Acute grade 3 or 4 hematologic toxicities in the CRT arm were significantly higher than in the RT alone arm (6.2% vs. 31.2%, p=0.010). CONCLUSION: Adjuvant pelvic concurrent chemoradioherapy did not show superior results in overall survival and relapse-free survival compared to RT alone in stage I-II endometrial carcinoma.

Evaluation of the Flash effect in breast irradiation using TomoDirect: an investigational study.

Flash is a specified function in TomoDirect that enables beam expansion by opening additional leaves to the target. This study assessed the theoretical dose distribution resulting from Flash in breast irradiation using TomoDirect. A cylindrical phantom that enabled dose distribution of the breast was used for verifying the effect of planning target volume (PTV) contouring and Flash. A total of 18 Gy in 10 fractions were prescribed to the PTV. Five PTVs were then created by Contracting this contour by 0, 1, 2, 3, 4 and 5 mm, giving PTV-x. Flash ±x is defined by opening x (number) of the leaves. The Flash effect in the air was compared with each set-up error of 5, 10 and 15 mm, respectively. The minimum PTV dose from PTV-1 to PTV-3 increased from 13.88 Gy to 15.86 Gy. In contrast, Dmin in PTV-4 and PTV-5 was 17.80 Gy in 98.88% of the prescription dose. Without Flash, when 5-, 10- and 15-mm set-up errors applied in the PTV, relative doses of 87.88, 23.73 and 7.94% were observed, respectively. However, in Flash 3, which was equal to the usual air margin of 1.875 cm, a relative dose of 104.24% ± 0.30% was observed, irrespective of set-up errors (5 mm to 15 mm). Flash opening is useful for countervailing set-up errors in breast cancer patients who receive breast irradiation with TomoDirect.

KRAS Mutation Status Is Not a Predictor for Tumor Response and Survival in Rectal Cancer Patients Who Received Preoperative Radiotherapy With 5-Fluoropyrimidine Followed by Curative Surgery.

We evaluated the tumor response and survival according to the KRAS oncogene status in locally advanced rectal cancer. One hundred patients with locally advanced rectal cancer (cT3-4N0-2M0) received preoperative radiation of 50.4 Gy in 28 fractions with 5-fluorouracil and total mesorectal excision. Tumor DNA from each patient was obtained from pretreatment biopsy tissues. A Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was found in 26 (26%) of the 100 patients. Downstaging (ypT0-2N0M0) rates after preoperative chemoradiotheray were not statistically different between the wild-type and mutant-type KRAS groups (30.8% vs 27.0%, P = 0.715, respectively). After a median follow-up time of 34 months, there was no statistically significant difference in the 3-year relapse-free survival (82.2% vs 82.6%, P = 0.512) and overall survival (94.7% vs 92.3%, P = 0.249) rates between wild-type and mutant-type KRAS groups, respectively. The KRAS mutation status does not influence the tumor response to the radiotherapy and survival in locally advanced rectal cancer patients who received preoperative chemoradiotherapy and curative surgery.

Setup Error and Effectiveness of Weekly Image-Guided Radiation Therapy of TomoDirect for Early Breast Cancer.

PURPOSE: This study investigated setup error and effectiveness of weekly image-guided radiotherapy (IGRT) of TomoDirect for early breast cancer. MATERIALS AND METHODS: One hundred and fifty-one breasts of 147 consecutive patients who underwent breast conserving surgery followed by whole breast irradiation using TomoDirect in 2012 and 2013 were evaluated. All patients received weekly IGRT. The weekly setup errors from simulation to each treatment in reference to chest wall and surgical clips were measured. Random, systemic, and 3-dimensional setup errors were assessed. Extensive setup error was defined as 5 mm above the margin in any directions. RESULTS: All mean errors were within 3 mm of all directions. The mean angle of gantry shifts was 0.6°. The mean value of absolute 3-dimensional setup error was 4.67 mm. In multivariate analysis, breast size (odds ratio, 2.82; 95% confidence interval, 1.00 to 7.90) was a significant factor for extensive error. The largest significant deviation of setup error was observed in the first week of radiotherapy (p < 0.001) and the deviations gradually decreased with time. The deviation of setup error was 5.68 mm in the first week and within 5 mm after the second week. CONCLUSION: In this study, there was a significant association between breast size and significant setup error in breast cancer patients who received TomoDirect. The largest deviation occurred in the first week of treatment. Therefore, patients with large breasts should be closely observed on every fraction and fastidious attention is required in the first fraction of IGRT.