Incidental Axillary Dose of Tomotherapy in Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer: A Dosimetrical Analysis.

Background and Objectives: Intensity-modulated radiation therapy (IMRT) is becoming a more common method of performing whole breast irradiation (WBI) for early breast cancer. This study aimed to examine the incidental dose to the axillary region using tomotherapy, a unique form of IMRT. Patients and Methods: This study included 30 patients with early-stage breast cancer who underwent adjuvant WBI using TomoDirect IMRT. A hypofractionation scheme of 42.4 Gy delivered in 16 fractions was prescribed. The plan comprised of two parallel-opposed beams, along with two additional beams positioned anteriorly at gantry angles of 20° and 40° from the medial beam. The incidental dose received at axillary levels I, II, and III was evaluated using several dose-volume parameters. Results: The study participants had a median age of 51 years, and 60% had left-sided breast cancer. The mean dose of the axilla for levels I, II, and III were 15.5 ± 4.8 Gy, 14.9 ± 4.2 Gy, and 1.5 ± 1.6 Gy, respectively. Adequate coverage of the axilla, defined as V95%[%], was achieved for 4.7 ± 3.9%, 4.8 ± 3.7%, and 0 ± 0% for levels I, II, and III, respectively. The results were compared with those of previously published studies, and the axillary mean dose and V95%[%] of TomoDirect IMRT were low, comparable to other IMRT techniques, and lower than those of traditional tangential therapy. Conclusions: While incidental axillary radiation during WBI has been proposed to assist in regional disease control, the TomoDirect plan was demonstrated to decrease this dose, and a hypofractionation scheme would further lower its biological effectiveness. Future clinical studies should incorporate dosimetrical analysis of incidental axillary dose, in order to facilitate hypofractionated IMRT planning with risk-adjusted axilla coverage in early breast cancer.

Stereotactic ablative radiotherapy for pulmonary oligometastases from primary hepatocellular carcinoma: a multicenter and retrospective analysis (KROG 17-08).

OBJECTIVE: Hypofractionated radiotherapy has recently been applied to treat pulmonary metastases of hepatocellular carcinoma. However, there is no definite evidence on its safety and efficacy. We evaluate the clinical outcomes of hypofractionated radiotherapy for oligo pulmonary metastases of hepatocellular carcinoma in the multicenter and retrospective study. METHODS: From March 2011 to February 2018, 58 patients with fewer than five pulmonary metastases of hepatocellular carcinoma who underwent hypofractionated radiotherapy in nine tertiary university hospitals were analyzed retrospectively. The primary endpoint was the local control rate. The secondary endpoints were overall survival, progression-free survival, prognostic factors affecting the treatment outcomes and treatment-related side effects. RESULTS: The local tumor response rate including complete and partial response was 77.6% at 3 months after hypofractionated radiotherapy. The median survival and progression-free survival times were 20.9 and 5.3 months, respectively. The 1-year overall survival and progression-free survival rates were 65.5 and 22.4%, respectively. The good treatment response after hypofractionated radiotherapy (P = 0.001), the absence of intrahepatic tumor (P = 0.004) and Child-Pugh class A (P = 0.010) were revealed as significant prognostic factors for overall survival in the multivariate analysis. A progression-free interval of <6 months (P = 0.009) was a negative prognostic factor for overall survival in the multivariate analysis. Of 58 patients, five (8.6%) had grade 2 or higher radiation pneumonitis after hypofractionated radiotherapy. CONCLUSIONS: The favorable local control rate and acceptable toxicity indicate the clinical usefulness of hypofractionated radiotherapy for hepatocellular carcinoma patients who have less than five pulmonary metastases.

Isoprenyl carboxyl methyltransferase inhibitors: a brief review including recent patents.

Among the enzymes involved in the post-translational modification of Ras, isoprenyl carboxyl methyltransferase (ICMT) has been explored by a number of researchers as a significant enzyme controlling the activation of Ras. Indeed, inhibition of ICMT exhibited promising anti-cancer activity against various cancer cell lines. This paper reviews patents and research articles published between 2009 and 2016 that reported inhibitors of ICMT as potential chemotherapeutic agents targeting Ras-induced growth factor signaling. Since ICMT inhibitors can modulate Ras signaling pathway, it might be possible to develop a new class of anti-cancer drugs targeting Ras-related cancers. Researchers have discovered indole-based small-molecular ICMT inhibitors through high-throughput screening. Researchers at Duke University identified a prototypical inhibitor, cysmethynil. At Singapore University, Ramanujulu and his colleagues patented more potent compounds by optimizing cysmethynil. In addition, Rodriguez and Stevenson at Universidad Complutense De Madrid and Cancer Therapeutics CRC PTY Ltd., respectively, have developed inhibitors based on formulas other than the indole base. However, further optimization of chemicals targeted to functional groups is needed to improve the characteristics of ICMT inhibitors related to their application as drugs, such as solubility, effectiveness, and safety, to facilitate clinical use.

Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer.

Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response to CRT would be valuable for individualizing treatment for LARC patients. The current study used metabolomics-based approaches to identify molecular markers that predict the response to CRT. Seventy-six patients with LARC who received pelvic radiotherapy and concurrent chemotherapy using tegafur-uracil and leucovorin were enrolled. Radical surgery was performed 6-8 weeks after the completion of CRT. The postsurgical pathological CRT response was evaluated using the ypStage or tumor regression grade. Profiling patterns of low-mass ions (LMIs) in the pretreatment sera were obtained from all patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Our previously developed two-step algorithms, which showed a powerful diagnostic capability during colorectal cancer screening, were then used to screen for meaningful LMIs with discriminatory power. One combination consisting of seven LMIs was identified, whose discriminatory score separated a good CRT response (ypStage 0-1) from a poor CRT response (ypStage 3-4) successfully. However, each individual LMI alone showed insignificant discriminatory power. This finding suggests that analysis of the LMIs in pretreatment serum could serve as a predictive marker of the CRT response in patients with LARC.

Decreased cellular levels of palmitic amide are linked to 5-fluorouracil resistance in human colon cancer cells.

BACKGROUND/AIMS: The aim of this study was to investigate whether profiling metabolic compounds in human colon cancer cells with induced 5-florouracil resistance enables identification of predictive biomarkers for 5-florouracil resistance. METHODOLOGY: 5-florouracil resistant and parental cells were extracted using methanol/chloroform solution, and analyzed by MALDI-TOF. Principal components analysis and discriminant analysis was performed to select low-mass ions with strong discriminating power between 5-florouracil resistant and parental cells. The correlation between the intensities of low-mass ions and intrinsic 5-florouracil resistance in 11 colon cancer cells was analyzed using the Spearman rank coefficient. RESULTS: Eleven low-mass ions had strong discrimi-nating power between 5-florouracil-resistant and parental cells. Of these, the intensity of a low-mass ion with 256.29 m/z was negatively correlated with intrinsic 5-florouracil resistance in 11 colon cancer cells (r = -0.6545, P = 0.0338). By searching the H+ adduct with 0.05 m/z tolerance in the Human Metabolome Database, a low-mass ion of 256.29 m/z was identified as palmitic amide. Interestingly, extracellular treatment with palmitic amide reduced 5-florouracil resistance and invasiveness in 5-florouracil-resistant cells. CONCLUSIONS: Palmitic amide showed potential not only as a predictor of 5-florouracil resistance, but also for reduction of 5-florouracil resistance in colon cancer cells.

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study.

PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Comparison between Two-Dimensional and Point Shear Wave Elastography Techniques in Evaluating Liver Fibrosis Using Histological Staging as the Reference Standard: A Prospective Pilot Study.

Evaluation of hepatic fibrosis is essential to prevent liver-related morbidity and mortality. Although various types of ultrasound shear wave elastography (SWE) have been used and validated, there are limited studies on the relatively newer technique, two-dimensional SWE (2D-SWE). Therefore, this study aimed to compare the diagnostic performances of 2D-SWE and point SWE (p-SWE) for evaluating liver fibrosis using histology as the reference standard. To measure liver stiffness (LS) values, 87 patients underwent 2D-SWE and p-SWE using the same machine. Technical failures and unreliable measurements were also evaluated. The diagnostic performances of 2D-SWE and p-SWE were compared using area under the receiver operating characteristic (AUROC) curve analysis. No technical failures were observed in either method; however, unreliable measurements were less frequent in 2D-SWE (1/87 [1.1%]) than in p-SWE (8/87 [9.2%]) (p < 0.001). The AUROC of the LS values of 2D-SWE were significantly higher than those of p-SWE for diagnosing significant fibrosis (0.965 vs. 0.872, p = 0.022) and cirrhosis (0.994 vs. 0.886, p = 0.042). In conclusion, 2D-SWE is more reliable and accurate than p-SWE for diagnosing hepatic fibrosis.

Evaluating the Necessity of Adaptive RT and the Role of Deformable Image Registration in Lung Cancer with Different Pathologic Classifications.

BACKGROUND: This study aimed to analyze differential radiotherapy (RT) responses according to the pathological type of lung cancer to see the possibility of applying adaptive radiotherapy (ART). METHODS: ART planning with resampled-computed tomography was conducted for a total of 30 patients (20 non-small-cell lung cancer patients and 10 small-cell lung cancer patients) using a deformable image registration technique to reveal gross tumor volume (GTV) changes according to the duration of RT. RESULTS: The small-cell lung cancer group demonstrated an average GTV reduction of 20.95% after the first week of initial treatment (p = 0.001), whereas the adenocarcinoma and squamous cell carcinoma groups showed an average volume reduction of 20.47% (p = 0.015) and 12.68% in the second week. The application of ART according to the timing of GTV reduction has been shown to affect changes in radiation dose irradiated to normal tissues. This suggests that ART applications may have to be different depending on pathological differences in lung cancer. CONCLUSION: Through these results, the present study proposes the possibility of personalized treatment options for individual patients by individualizing ART based on specific radiation responses by pathologic types of lung cancer.

Up-regulated expression of l-caldesmon associated with malignancy of colorectal cancer.

BACKGROUND: Caldesmon (CaD), a major actin-associated protein, is found in smooth muscle and non-muscle cells. Smooth muscle caldesmon, h-CaD, is a multifunctional protein, and non-muscle cell caldesmon, l-CaD, plays a role in cytoskeletal architecture and dynamics. h-CaD is thought to be an useful marker for smooth muscle tumors, but the role(s) of l-CaD has not been examined in tumors. METHODS: Primary colon cancer and liver metastasis tissues were obtained from colon cancer patients. Prior to chemoradiotherapy (CRT), normal and cancerous tissues were obtained from rectal cancer patients. Whole-tissue protein extracts were analyzed by 2-DE-based proteomics. Expression and phosphorylation level of main cellular signaling proteins were determined by western blot analysis. Cell proliferation after CaD siRNA transfection was monitored by MTT assay. RESULTS: The expression level of l-CaD was significantly increased in primary colon cancer and liver metastasis tissues compared to the level in the corresponding normal tissues. In cancerous tissues obtained from the patients showing poor response to CRT (Dworak grade 4), the expression of l-CaD was increased compared to that of good response group (Dworak grade 1). In line with, l-CaD positive human colon cancer cell lines were more resistant to 5-fluorouracil (5-FU) and radiation treatment compared to l-CaD negative cell lines. Artificial suppression of l-CaD increased susceptibility of colon cancer cells to 5-FU, and caused an increase of p21 and c-PARP, and a decrease of NF-kB and p-mTOR expression. CONCLUSION: Up-regulated expression of l-CaD may have a role for increasing metastatic property and decreasing CRT susceptibility in colorectal cancer cells.

Hydroxymethylglutaryl-coenzyme a synthase 2 expression is associated with chemoradiotherapy responses in colorectal cancer.

BACKGROUND: Preoperative chemoradiotherapy has become a standard treatment modality for locally advanced rectal cancer. Favorable long-term outcomes have been reported for patients with good responses to chemoradiotherapy. Therefore, predictive factors for chemoradiotherapy responses can be useful for their applicability to risk-adaptive therapy in patients with colorectal cancer. OBJECTIVE: The aim of this study was to investigate whether hydroxymethylglutaryl-coenzyme A synthase 2, a key enzyme in ketogenesis, is associated with the responses of colorectal cancer cells to chemoradiotherapy. DESIGN: Hydroxymethylglutaryl-coenzyme A synthase 2 was identified by a 2-dimensional gel electrophoresis -based proteome analysis. It was analyzed in 12 colorectal cancer cells for associations with radiation or 5-fluorouracil susceptibility by Western blotting, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium Bromide assay, and small interfering RNA transfection. Then, tumor tissues obtained from 45 patients with rectal cancer before chemoradiotherapy were analyzed by Western blotting for associations with chemoradiotherapy responses. RESULTS: Expression of hydroxymethylglutaryl-coenzyme A synthase 2 was significantly correlated with intrinsic radiation resistance of 12 cancer cells. Hydroxymethylglutaryl-coenzyme A synthase 2 expression was significantly affected by treatment with either 5-fluorouracil or radiation depending on cell types. The artificial suppression of hydroxymethylglutaryl-coenzyme A synthase 2 did not result in the change of chemoradiation susceptibility in colorectal cancer cells. Nevertheless, in multivariate analyses, hydroxymethylglutaryl-coenzyme A synthase 2 expression in rectal cancer tissues was shown to be a significant predictive factor for chemoradiotherapy responses, as evaluated in terms of tumor regression grade and downstaging. LIMITATIONS: Overall findings in vitro showed that the expression level of hydroxymethylglutaryl-coenzyme A synthase 2 was highly variable depending on colon cancer cell types, and it cannot directly affect on chemoradiotherapy responses. The molecular mechanism underpinning the association between hydroxymethylglutaryl-coenzyme A synthase expression and chemoradiotherapy responses needs to be elucidated through future research. CONCLUSIONS: Hydroxymethylglutaryl-coenzyme A synthase 2 was associated with the effects of chemoradiotherapy on human colorectal cancer cells. Pretreatment levels of hydroxymethylglutaryl-coenzyme A synthase 2 in rectal cancer may be useful in predicting the responses to chemoradiotherapy.

Endorectal balloon (ERB) in helical tomotherapy (HT) for localized prostate cancer: a case report of dosimetric analysis.

Radiation therapy (RT) for localized prostate cancer yields oncological outcomes similar to those following radical prostatectomy, but is associated with more anorectal toxicity. An endorectal balloon (ERB) has been utilized to decrease the incidental dose to the rectal wall. However, few studies analyzed whether the ERB can further spare the rectum in helical tomotherapy (HT), which by itself can be used to treat prostate cancer while minimizing irradiation of surrounding critical tissues. Here, we report a 64-year-old man with pathologically proven prostate adenocarcinoma (stage T2cN0M0). He underwent definitive RT using HT with a hypofractionated scheme of 70 Gy in 28 fractions. Simulation CT was performed twice: with and without ERB application. The ERB was filled with 70 mL of air. Two intensity-modulated RT (IMRT) plans were generated for each CT image set (with and without ERB) and compared about the dose to the anorectum. The rectal volume receiving ≥40 Gy (V40Gy) was reduced from 43.4% to 34.6% with ERB use (20.3% reduction). This reduction rate increased continuously up to V70Gy (48.2% reduction). The anal volume reduction was approximately 50% from V5Gy to V15Gy. The patient tolerated all ERB insertions well and there were no severe acute toxicities. ERB had a further anorectal-sparing effect in this case of prostate cancer treated by highly conformal HT, beyond the generally recommended dose-volume constraints of hypofractionated IMRT.

Choroid plexus carcinoma with leptomeningeal spread in an adult: a case report and review of the literature.

BACKGROUND: Choroid plexus carcinoma is an intraventricular neoplasm originating from the choroid plexus epithelium and is of rare occurrence in adults. However, owing to the low prevalence of choroid plexus carcinoma, there is very limited information about the disease entity and treatment. Here we report a rare case of choroid plexus carcinoma in an adult patient. CASE PRESENTATION: A 46-year-old South Korean (East Asian) male presented with low back pain, headache, and diplopia. Magnetic resonance imaging demonstrated enhancing mass lesion in the left trigone, cerebellar with leptomeningeal spread. Surgery was performed via left parietal craniotomy, and the lesion was histologically confirmed to be choroid plexus carcinoma. The patient received adjuvant craniospinal irradiation for remnant mass and leptomeningeal spread. Magnetic resonance imaging performed immediately after completion of the treatment revealed a partial decrease in the size of the tumor. However, the patient expired died as a result of acute respiratory distress syndrome before follow-up of long-term outcome. CONCLUSION: Choroid plexus carcinoma with leptomeningeal spread in adults is very important for rapid diagnosis and treatment. In the case of the presence of leptomeningeal spread, craniospinal irradiation can be considered as a treatment method, but may have serious complications. Hence, the technique should be applied with care.

Computed Tomography Findings Associated with Treatment Failure after Antibiotic Therapy for Acute Appendicitis.

OBJECTIVE: To identify the CT findings associated with treatment failure after antibiotic therapy for acute appendicitis. MATERIALS AND METHODS: Altogether, 198 patients who received antibiotic therapy for appendicitis were identified by searching the hospital's surgery database. Selection criteria for antibiotic therapy were uncomplicated appendicitis with an appendiceal diameter equal to or less than 11 mm. The 86 patients included in the study were divided into a treatment success group and a treatment failure group. Treatment failure was defined as a resistance to antibiotic therapy or recurrent appendicitis during a 1-year follow-up period. Two radiologists independently evaluated the following CT findings: appendix-location, involved extent, maximal diameter, thickness, wall enhancement, focal wall defect, periappendiceal fat infiltration, and so on. For the quantitative analysis, two readers independently measured the CT values at the least attenuated wall of the appendix by drawing a round region of interest on the enhanced CT (HUpost) and non-enhanced CT (HUpre). The degree of appendiceal wall enhancement (HUsub) was calculated as the subtracted value between HUpost and HUpre. A logistic regression analysis was used to identify the CT findings associated with treatment failure. RESULTS: Sixty-four of 86 (74.4%) patients were successfully treated with antibiotic therapy, with treatment failure occurring in the remaining 22 (25.5%). The treatment failure group showed a higher frequency of hypoenhancement of the appendiceal wall than the success group (31.8% vs. 7.8%; p = 0.005). Upon quantitative analysis, both HUpost (46.7 ± 21.3 HU vs. 58.9 ± 22.0 HU; p = 0.027) and HUsub (26.9 ± 17.3 HU vs. 35.4 ± 16.6 HU; p = 0.042) values were significantly lower in the treatment failure group than in the success group. CONCLUSION: Hypoenhancement of the appendiceal wall was significantly associated with treatment failure after antibiotic therapy for acute appendicitis.

Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer: long-term outcomes and prognostic significance of pathologic nodal status (KROG 09-01).

OBJECTIVE: To investigate long-term outcomes of locally advanced rectal cancer (LARC) patients with postchemoradiotherapy (post-CRT) pathologic complete response of primary tumor (ypT0) and determine prognostic significance of post-CRT pathologic nodal (ypN) status. BACKGROUND: LARC patients with post-CRT pathologic complete response were suggested to have favorable long-term outcomes, but prognostic significance of ypN status has never been specifically defined in ypT0 patients. METHODS: The Korean Radiation Oncology Group collected clinical data for 333 LARC patients with ypT0 following preoperative CRT and curative radical resections between 1993 and 2007. Sphincter preservation surgery and abdominoperineal resection were performed in 283 (85.0%) and 50 (15.0%) patients, respectively. Postoperative chemotherapy was given to 285 (85.6%) patients. Survival was estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used in multivariate analyses. RESULTS: After median follow-up of 43 (range = 14-172) months, 5-year disease-free survival (DFS) was 84.6% and overall survival (OS) was 92.8%. The ypN status was ypT0N0 in 304 (91.3%), ypT0N1 in 22 (6.6%), and ypT0N2 in 7 (2.1%) patients. The ypN status was the most relevant independent prognostic factor for both DFS and OS in ypT0 patients. The 5-year DFS and OS was 88.5% and 94.8% in ypT0N0 patients, and 45.2% and 72.8% in ypT0N+ patients (both, P < 0.001). CONCLUSIONS: LARC patients achieving ypT0N0 after preoperative CRT had favorable long-term outcomes, whereas positive ypN status had a poor prognosis even after total regression of primary tumor.

Local excision following pre-operative chemoradiotherapy-induced downstaging for selected cT3 distal rectal cancer.

OBJECTIVE: To investigate the long-term outcomes of selected patients with cT3 distal rectal cancer treated with local excision following pre-operative chemoradiotherapy. METHODS: Between January 2003 and February 2008, 11 patients with cT3 distal rectal cancer received a local excision following pre-operative chemoradiotherapy. The median age of the patients was 61 years (range, 42-71). The median tumor size was 3 cm (range, 2-5), and the median distance of the caudal tumor edge from the anal verge was 3 cm (range, 1-4). Clinical lymph node status was positive in five patients. Pre-operative chemoradiotherapy consisted of a 50.4 Gy in 28 fractions with concurrent chemotherapy. A transanal full-thickness local excision was performed after a median of 54 days (range, 31-90) from chemoradiotherapy completion. Ten patients received post-operative chemotherapy. RESULTS: Pathologically complete responses occurred in eight patients, ypT1 in two and ypT2 in one. The pathologic tumor size for three ypT1-2 tumors was 0.9, 1.1 and 2.2 cm. The follow-up period was a median of 59 months (range, 24-85). One patient (ypT0) developed recurrence at the excision site 14 months after surgery, but was successfully salvaged with an abdominoperineal resection and adjuvant chemotherapy. Another patient (ypT2) developed bone metastasis after 8 months and died of the disease. The 5-year local recurrence-free, disease-free and overall survival rates were 90.9%, 81.8% and 88.9%, respectively. No Grade 3 or worse gastrointestinal toxicity was detected. CONCLUSIONS: Full-thickness local excision following chemoradiotherapy may be an acceptable option for cT3 distal rectal cancer that responds well to chemoradiotherapy.

Relationship Between Changes in Myocardial F-18 Fluorodeoxyglucose Uptake and Radiation Dose After Adjuvant Three-Dimensional Conformal Radiotherapy in Patients with Breast Cancer.

This study aimed to assess the relationship between radiation dose and changes in the irradiated myocardial F-18 fluorodeoxyglucose (FDG) uptake after radiotherapy (RT) in breast cancer patients. The data of 55 patients with left and 48 patients with right breast cancer who underwent curative surgical resection and adjuvant three-dimensional conformal RT and staging (PET1), post-adjuvant chemotherapy (PET2), post-RT (PET3), and surveillance (PET4) FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. The median interval between PET1 and curative surgical resection, between the end of adjuvant chemotherapy and PET2, between the end of RT and PET3, and between the end of RT and PET4 were five days, 13 days, 132 days, and 353 days, respectively. The myocardial-to-blood pool uptake ratio was measured in all patients. For patients with left breast cancer, the 30 Gy- (30 Gy) and 47.5 Gy-irradiated myocardium-to-low-irradiated myocardium (47.5 Gy) FDG uptake ratios were additionally measured. There were no differences in the myocardial-to-blood pool uptake ratios between left and right breast cancer on all PET scans. For left breast cancer, higher 30 Gy and 47.5 Gy uptake ratios were observed on PET3 than on PET1 and PET2. Both uptake ratios decreased on PET4 compared to PET3, but, were still higher compared to PET1. On PET3 and PET4, the 47.5 Gy were higher than the 30 Gy uptake ratios, while there were no differences between them on PET1 and PET2. Although the whole myocardium FDG uptake showed no significant change, the irradiated myocardium FDG uptake significantly increased after RT and was related to radiation dose to the myocardium in breast cancer patients. These results might be an imaging evidence that supports the increased risk of heart disease after RT in patients with left breast cancer.

Dosimetric comparison of incidental axillary irradiation between three-dimensional conformal and volumetric modulated arc techniques for breast cancer.

Radiotherapy techniques for breast cancer have evolved with efforts to reduce treatment-related side effects. In the present study, we conducted dosimetric analysis of incidental axillary irradiation between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3D-CRT). A total of 20 patients with early stage left breast cancer who underwent breast-conserving surgery followed by postoperative radiotherapy were analyzed. For VMAT plans, dose-volume constraints were not imposed on the axilla, as with 3D-CRT. We compared the dosimetric parameters of the planning target volumes, organs at risk and axillary level I-III of the two plans. VMAT showed better target coverage and a normal organ-sparing effect compared with 3D-CRT. The incidental axillary irradiation of VMAT was lower; the mean dose and the V40Gy were significantly reduced at all axillary levels, with the exception of no difference in the maximum dose to axillary level I. In conclusion, VMAT decreased incidental axillary irradiation, even in the absence of a dose-volume constraint on the axilla, and can, therefore, decrease the risk of radiotherapy-related lymphedema. However, caution is also required because it is unclear whether this incidental axillary irradiation is beneficial for reducing recurrence on the axilla.

Stereotactic body radiation therapy for pulmonary large cell neuroendocrine carcinoma: a case report.

The incidence of large cell neuroendocrine carcinoma (LCNEC) of the lung is rare, and the treatment methods and prognosis for such patients are still subjects of debate. We report a case of a 78-year-old male LCNEC patient for whom stereotactic body radiation therapy was performed. A four-dimensional computed tomography scan was used for simulation, and radiotherapy was planned using the volumetrically modulated arc technique. A total of 55 Gy was delivered in five daily fractions. The treatment was safely completed, and the patient did not report any discomfort. The only side-effect was an intermittent cough. Currently, the patient has received 18 months of outpatient follow-up care with no evidence of disease. In conclusion, stereotactic body radiation therapy can be a valuable treatment option for early stage LCNEC.

Cyclooxygenase-2 expression as a predictor of para-aortic lymph node recurrence in uterine cervical cancer.

PURPOSE: The overexpression of cyclooxygenase-2 (COX-2) is associated with a worse prognosis and the development of distant metastases in cervical cancer. This matched-pair analysis examined whether COX-2 expression is associated with para-aortic lymph node (PALN) recurrence in uterine cervical cancer treated with radiotherapy (RT). METHODS AND MATERIALS: For this study, we matched 20 patients with PALN recurrence after definitive or postoperative RT by stage with 20 others who did not have PALN recurrence. Of the 20 patients with PALN recurrence, definitive or postoperative RT was performed in 11 and 9 patients, respectively. COX-2 expression was assessed immunohistochemically using a mouse monoclonal antibody on formalin-fixed paraffin-embedded tumor specimens taken before RT. A logistic regression model was used to predict for PALN recurrence. RESULTS: COX-2 was expressed in 28 (70%) of the 40 patients. The staining intensity was as follows: weak in 19 (47%), moderate in 6 (15%), and strong in 3 (8%) patients. The patients with PALN recurrence had much greater expression of COX-2 (17 patients, 85%) than did the control group (11 patients, 55%; p = 0.04). Strong staining intensity of COX-2 was seen only in the PALN recurrence group. The statistically significant factors associated with PALN recurrence were positive pelvic lymph nodes (odds ratio, 7.61; 95% confidence interval, 1.55-37.37; p = 0.01) and COX-2 expression (odds ratio, 1.47; 95% confidence interval, 1.04-2.09; p = 0.03). CONCLUSION: Our findings suggest that COX-2 overexpression in the initial tumor tissue might be associated with PALN recurrence after RT in cervical cancer patients.