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Despite a considerable expansion in the present therapeutic repertoire for other malignancy managements, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. Moreover, the second primary cancer (SPC) diagnoses increased in patients with HNC, but studies providing evidence to support SPCs prediction in HNC are lacking. Several base classifiers are integrated forming an ensemble meta-classifier using a stacked ensemble method to predict SPCs and find out relevant risk features in patients with HNC. The balanced accuracy and area under the curve (AUC) are over 0.761 and 0.847, with an approximately 2% and 3% increase, respectively, compared to the best individual base classifier. Our study found the top six ensemble risk features, such as body mass index, primary site of HNC, clinical nodal (N) status, primary site surgical margins, sex, and pathologic nodal (N) status. This will help clinicians screen HNC survivors before SPCs occur.

Background: For advanced breast cancer with lymph node involvement, adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) has been indicated to reduce cancer recurrence and mortality. However, an extensive RT volume is associated with normal organ exposure, which increases the toxicity and affects patient outcomes. Modern arc RT techniques can improve normal organ sparing compared with conventional techniques. The aim of this study was to explore the optimal technique for left-breast RT with RNI., Methods: We retrospectively reviewed patients receiving RT with RNI for left-breast cancer. We used modern arc RT techniques with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT) with a novel block technique, and compared differences in dosimetry parameters between the two groups. Subgroup analysis of RNI with or without internal mammary node (IMN) volume was also performed., Results: A total of 108 eligible patients were enrolled between 2017 and 2020, of whom 70 received VMAT and 38 received HT. The median RT dose was 55 Gy. No significant differences were found regarding the surgery, RT dose, number of fractions, target volume, and RNI volume between the VMAT and HT groups. VMAT reduced the heart mean dose more than HT (3.82 vs. 5.13 Gy, p < 0.001), as well as the cardiac parameters of V5-V20, whole-lung mean dose, lung parameters of V5-V20, and contralateral-breast and esophagus mean dose. In the subgroup analysis of RNI with IMNs, the advantage of VMAT persisted in protecting the heart, lung, contralateral breast, and esophagus. HT was beneficial for lowering the thyroid mean dose. For RNI without IMN, VMAT improved the low-dose exposure of the heart and lung, but HT was similar to VMAT in terms of heart, whole-lung, and contralateral-breast mean dose., Conclusions: For patients with left-breast cancer receiving adjuvant RT with RNI, VMAT reduced the exposure dose to the heart, lung, contralateral breast, and esophagus compared with HT. VMAT was superior to HT in terms of normal organ sparing in the patients who underwent RNI with IMN irradiation. Considering the reduction in normal organ exposure and potential toxicity, VMAT is the optimal technique for patients receiving RNI when deep inspiration breath-hold is not available.

Recent studies have indicated that cancer treatment based on immunotherapy alone is not viable. Combined treatment with other strategies is required to achieve the expected therapeutic effect. Reactive oxygen species (ROS) play an important role in regulating cancer cells and the tumor microenvironment, even in immune cells. However, rigorous regulation of the ROS level within the entire tumor tissue is difficult, limiting the application of ROS in cancer therapy. Therefore, we design an early phago-/endosome-escaping micelle that can release platinum-based drugs into the cytoplasm of macrophages and cancer cells, thereby enhancing the ROS levels of the entire tumor tissue; inducing apoptosis of cancer cells, down-regulation of CD47 expression of cancer cells, polarization of M1 macrophages, and phagocytosis of cancer cells by M1 macrophages; and achieving the dual effect of chemotherapy and macrophage-mediated immunotherapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.

Although boron neuron capture therapy (BNCT) has enabled the delivery of stronger radiation dose to glioblastoma multiforme (GBM) cells for precision radiotherapy (RT), patients in need are almost unable to access the treatment due to insufficient operating devices. Therefore, we developed targeted sensitization-enhanced radiotherapy (TSER), a strategy that could achieve precision cell-targeted RT using common linear accelerators. TSER, which involves the combination of GoldenDisk (GD; a spherical radioenhancer), 5-aminolevulinic acid (5-ALA), low-intensity ultrasound (US), and low-dose RT, exhibited synergized radiosensitization effects. Both 5-ALA and hyaluronic-acid-immobilized GD can selectively accumulate in GBM to induce chemical and biological enhancement of radiosensitization, resulting in DNA damage, escalation of reactive oxygen species levels, and cell cycle redistribution, in turn sensitizing GBM cells to radiation under US. TSER showed an enhanced therapeutic effect and survival in the treatment of an orthotropic GBM model with only 20% of the radiation dose compared to that of a 10-Gy RT. The strategy with the potential to inhibit GBM progress and rescue the organ at risk using low-dose RT, thereby improving the quality of life of GBM patients, shedding light on achieving cell-targeted RT using universally available linear accelerators. STATEMENT OF SIGNIFICANCE: We invented GoldenDisk (GD), a radioenhancer with hyaluronic-acid (HAc)-coated gold nanoparticle (AuNP)-core/silica shell nanoparticle, to make radiotherapy (RT) safer and smarter. The surface modification of HAc and silica allows GD to target CD44-overexpressed glioblastoma multiforme (GBM) cells and stay structurally stable in cytoplasm throughout the course of RT. By combining GD with low-energy ultrasound and an FDA-approved imaging agent, 5-aminolevulinic acid (5-ALA), GBM cells were sensitized to RT leaving healthy tissues in the vicinity unaffected. The ionized radiation can further be transferred to photoelectronic products with higher cytotoxicity by GD upon collision, achieving higher therapeutic efficacy. With the newly-developed strategy, we are able to achieve low-dose precision RT with the use of only 20% radiation dose., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

This study aims to develop a volume-based algorithm (VBA) that can rapidly optimize rotating gantry arc angles and predict the lung V 5 preceding the treatment planning. This phantom study was performed in the dynamic arc therapy planning systems for an esophageal cancer model. The angle of rotation of the gantry around the isocenter as defined as arc angle (θ A ), ranging from 360° to 80° with an interval of 20°, resulting in 15 different θ A of treatment plans. The corresponding predicted lung V 5 was calculated by the VBA, the mean lung dose, lung V 5 , lung V 20 , mean heart dose, heart V 30 , the spinal cord maximum dose and conformity index were assessed from dose-volume histogram in the treatment plan. Correlations between the predicted lung V 5 and the dosimetric indices were evaluated using Pearson's correlation coefficient. The results showed that the predicted lung V 5 and the lung V 5 in the treatment plan were positively correlated (r = 0.996, p < 0.001). As the θ A decreased, lung V 5 , lung V 20 , and the mean lung dose decreased while the mean heart dose, V 30 and the spinal cord maximum dose increased. The V 20 and the mean lung dose also showed high correlations with the predicted lung V 5 (r = 0.974, 0.999, p < 0.001). This study successfully developed an efficient VBA to rapidly calculate the θ A to predict the lung V 5 and reduce the lung dose, with potentials to improve the current clinical practice of dynamic arc radiotherapy.

Cone-beam computed tomography (CBCT) integrated with a linear accelerator is widely used to increase the accuracy of radiotherapy and plays an important role in image-guided radiotherapy (IGRT). For comparison with fan-beam computed tomography (FBCT), the image quality of CBCT is indistinct due to X-ray scattering, noise, and artefacts. We proposed a deep learning model, "Cycle-Deblur GAN", combined with CycleGAN and Deblur-GAN models to improve the image quality of chest CBCT images. The 8706 CBCT and FBCT image pairs were used for training, and 1150 image pairs were used for testing in deep learning. The generated CBCT images from the Cycle-Deblur GAN model demonstrated closer CT values to FBCT in the lung, breast, mediastinum, and sternum compared to the CycleGAN and RED-CNN models. The quantitative evaluations of MAE, PSNR, and SSIM for CBCT generated from the Cycle-Deblur GAN model demonstrated better results than the CycleGAN and RED-CNN models. The Cycle-Deblur GAN model improved image quality and CT-value accuracy and preserved structural details for chest CBCT images.

Purpose: Approximately 5%-10% of men who receive prostate cancer radiotherapy will suffer from radiation cystitis. Bladder filling before the administration of radiotherapy results in lower radiation exposure to the bladder. BladderScan, an ultrasound-based bladder volume scanner, has the potential to evaluate bladder volume during radiotherapy; thus, a prospective pilot study was initiated., Methods: Eleven men receiving tomotherapy for localized prostate cancer were enrolled. The validity of BladderScan was evaluated by comparing the measurements from BladderScan with the calculated volume from megavoltage computed tomography (MVCT). With a crossover design to compare different methods in bladder filling, the radiotherapy was divided into 2 sequences. Conventional method: the patient was asked to drink water after voiding urine. The amount of water and the duration of waiting were the same as in the setting of the simulation. BladderScan feedback method: the bladder filling procedure depended on the BladderScan measurements., Results: There were 314 sets of data from 11 patients. The correlation coefficient between V BS and V CT was 0.87, where V BS is the mean volume of 3 measurements by BladderScan and V CT is the bladder volume derived from MVCT. The BladderScan feedback method resulted in a significant larger bladder volume than the conventional method, with a mean difference of 36.9 mL. When the failure was defined as V CT <80% of planned volume, the BladderScan feedback method brought about a relative reduction in the failure rate with an odds ratio of 0.44 and an absolute reduction of 9.1%., Conclusion: The accuracy of BladderScan was validated by MVCT in our study. The BladderScan feedback method can help patients fill the bladder adequately, with a larger bladder volume and a lower failure rate.

Osteosarcoma is insensitive to radiation. High-dose radiation is often used as a treatment but causes side effects in patients. Hence, it is important to develop tumor cell-- targeted radiotherapy that could improve radiotherapy efficiency on tumor cells and reduce the toxic effect on normal cells during radiation treatment. In this study, we developed an innovative method for treating osteosarcoma by using a novel radiation-enhancer (i.e., carboxymethyl-hexanoyl chitosan-coated self-assembled Au@Fe3O4 nanoparticles; CSAF NPs). CSAF NPs were employed together with 5-aminolevulinic acid (5- ALA) to achieve tumor cell-targeted radiotherapy. In this study, osteosarcoma cells (MG63) and normal cells (MC3T3-E1) were used for an in vitro investigation, in which reactive oxygen species (ROS) assay, cell viability assay, clonogenic assay, and western blot were used to confirm the treatment efficiency. The ROS assay showed that the combination of CSAF NPs and 5-ALA enhanced radiation-induced ROS production in tumor cells (MG63); however, this was not observed in normal cells (MC3T3-E1). The cell viability ratio of normal cells to tumor cells after treatment with CSAF NPs and 5-ALA reached 2.79. Moreover, the clonogenic assay showed that the radiosensitivity of MG63 cells was increased by the combination use of CSAF NPs and 5-ALA. This was supported by performing a western blot that confirmed the expression of cytochrome c (a marker of cell mitochondria damage) and caspase-3 (a marker of cell apoptosis). The results provide an essential basis for developing tumor-cell targeted radiotherapy by means of low-- dose radiation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this study was to investigate the treatment of complicated keloids with helical tomotherapy (HT) and electron beam radiotherapy. From July 2018 to September 2018, 11 patients with 23 keloid lesions treated with HT were enrolled. Additionally, 11 patients with 20 lesions treated with electron beam radiotherapy in the same period were enrolled. Patients in both groups were treated within 24 h after surgical excision of the keloid lesion with 13.5 Gy in three consecutive daily fractions. The median follow-up period was 15 months. The local control rate was 91.3% and 80% in the HT group and the electron beam group, respectively. No acute adverse effects were observed in either group, but most patients exhibited pigmentation. No radiation-induced cancer occurred in these patients up to the time of this report. Pain and pruritus improved for all patients and more obviously for three patients with complicated keloids treated with HT. The measured surface dose was 103.7-112.5% and 92.8-97.6% of the prescribed dose in the HT group and the electron beam group, respectively. HT can be considered an alternative in cases where it is not feasible to use multiple electron fields, due to encouraging clinical outcomes.

Multifunctional nanoplatforms combined with photodynamic therapy (PDT) and anticancer drugs have shown great promising in cancer therapy. However, their efficacy is limited by the low specificity, low oxygen levels, and a tolerant tumor immune microenvironment. Herein, we developed a biocompatible theranostic nanoplatform (FM@VP) based on co-assembly of a nanocomplex formed by a functional polysaccharide fucoidan and a bioreducible polyamidoamine (PAMAM) dendrimer, a photosensitizer verteporfin (VP), and MnO 2 nanoparticles (a tumor microenvironment responsive oxygen evolving nanomaterial) into a multifunctional nanoparticle cluster. The dendrimer-fucoidan polyionic nanocomplex (DFPN) specifically targeted P-selectin-overexpressed triple-negative breast cancer (TNBC) and the tumor-associated vasculature, and was sensitive to glutathione (GSH) in tumor. More importantly, this FM@VP nanocomplex simultaneously overcame tumor hypoxia, suppressed oncogenic signaling, and attenuated tumor-mediated immunosuppression, resulting in improving therapeutic efficacy of PDT while enhancing antitumor immunity and anti-metastasis. This discovery provides a powerful strategy for synergetic cancer targeting/photodynamic/immunotherapy and could serve as a safe clinical translational approach., (Copyright © 2020. Published by Elsevier Ltd.)

Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer-related deaths. Thus, understanding the mechanism of lung cancer metastasis will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF-elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: To evaluate the feasibility and optimal restricted angle of the complete-directional-complete block (CDCB) technique in helical tomotherapy (HT) by including regional nodal irradiation (RNI) with the internal mammary node (IMN) in left-sided breast cancer., Methods: Ten left-sided breast cancer patients treated with 50 Gy in 25 fractions were compared with five-field intensity-modulated radiation therapy (5F-IMRT) and six types of HT plans. In the HT plans, complete block (CB), organ-based directional block (OBDB) and CDCB with different restricted angles were used., Results: The conformity index (CI) between the CDCB 0,10,15,20 and 5F-IMRT groups was similar. Compared to CB, OBDB and 5F-IMRT, CDCB 20 resulted in a decreased ipsilateral mean lung dose. The low-dose region (V 5 ) of the ipsilateral lung in OBDB (84.0%) was the highest among all techniques ( p < 0.001). The mean dose of the heart in CB was significantly reduced (by 11.5-22.4%) compared with other techniques. The V 30 of the heart in CDCB 20 (1.9%) was significantly lower than that of CB, OBDB and 5F-IMRT. Compared to the mean dose of the left anterior descending (LAD) artery of 5F-IMRT (27.0 Gy), CDCB 0 , CDCB 10 , CDCB 15 , CDCB 20 and OBDB reduced the mean dose effectively by 31.7%, 38.3%, 39.6%, 42.0 and 56.2%, respectively. Considering the parameters of the organs-at-risk (OARs), CDCB 10,15,20 had higher expectative values than the other techniques ( p = 0.01)., Conclusions: HT with the CDCB technique is feasible for treating left-sided breast cancer patients. The CDCB 10-20 techniques not only achieved similar planning target volume coverage, homogeneity and dose conformity but also allowed better sparing of the heart and bilateral lungs., Advances in Knowledge: For left-sided breast cancer patients whose RNI field includes the IMN, heart avoidance is an important issue. The CDCB technique achieved good PTV coverage, homogeneity and dose conformity and allowed better sparing of the mean dose of the lung, the LAD artery, and the heart and reduced the V 30 of the heart.

This study aimed to review clinical experiences using whole-field simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) and sequential IMRT in postoperative patients with oral cavity cancer (OCC). From November 2006 to December 2014, a total of 182 postoperative patients with OCC who underwent either SIB-IMRT (n = 63) or sequential IMRT (n = 119) were enrolled retrospectively and matched randomly according to multiple risk factors by a computer. The differences were well balanced after patient matching ( P = .38). The median follow-up time was 65 months. For patients treated with the SIB technique and the sequential technique, the respective mortality rates were 36.8% and 20.0% ( P = .04). The primary recurrence rates were 26.3% and 10.0% ( P = .02), respectively. The respective marginal failure rates were 26.7% and 16.7%. A multivariate logistic regression analysis showed that patients who received the SIB technique had a 2.74 times higher risk of death than those who received the sequential technique (95% confidence interval = 1.10-6.79, P = .03). Sequential IMRT provided a significantly lower dose to the esophagus (5.2 Gy, P = .02) and trachea (4.6 Gy, P = .03) than SIB-IMRT. For patients with locally advanced OCC, postoperative sequential IMRT may overcome an unpredictable geographic miss, potentially with a lower marginal failure rate in the primary area. Patients treated by sequential IMRT show equal overall survival benefits to those treated by SIB-IMRT and a lower mortality rate than those treated by SIB-IMRT. Additionally, a reduced dose to the esophagus and trachea compared to sequential IMRT was noted.

Background: In recent years, the development and diagnosis of secondary cancer have become the primary concern of cancer survivors. A number of studies have been developing strategies to extract knowledge from the clinical data, aiming to identify important risk factors that can be used to prevent the recurrence of diseases. However, these studies do not focus on secondary cancer. Secondary cancer is lack of the strategies for clinical treatment as well as risk factor identification to prevent the occurrence. Methods: We propose an effective ensemble feature learning method to identify the risk factors for predicting secondary cancer by considering class imbalance and patient heterogeneity. We first divide the patients into some heterogeneous groups based on spectral clustering. In each group, we apply the oversampling method to balance the number of samples in each class and use them as training data for ensemble feature learning. The purpose of ensemble feature learning is to identify the risk factors and construct a diagnosis model for each group. The importance of risk factors is measured based on the properties of patients in each group separately. We predict secondary cancer by assigning the patient to a corresponding group and based on the diagnosis model in this corresponding group. Results: Analysis of the results shows that the decision tree obtains the best results for predicting secondary cancer in the three classifiers. The best results of the decision tree are 0.72 in terms of AUC when dividing the patients into 15 groups, 0.38 in terms of F 1 score when dividing the patients into 20 groups. In terms of AUC, decision tree achieves 67.4% improvement compared to using all 20 predictor variables and 28.6% improvement compared to no group division. In terms of F 1 score, decision tree achieves 216.7% improvement compared to using all 20 predictor variables and 80.9% improvement compared to no group division. Different groups provide different ranking results for the predictor variables. Conclusion: The accuracies of predicting secondary cancer using k -nearest neighbor, decision tree, support vector machine indeed increased after using the selected important risk factors as predictors. Group division on patients to predict secondary cancer on the separated models can further improve the prediction accuracies. The information discovered in the experiments can provide important references to the personality and clinical symptom representations on all phases of guide interventions, with the complexities of multiple symptoms associated with secondary cancer in all phases of the recurrent trajectory., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: To evaluate the practicality of NS-21 cream with regard to its skin-related toxicity in patients with head and neck cancer (HNC) who are undergoing concurrent chemoradiation therapy (CCRT) or radiotherapy (RT)., Methods: Between July 2015 and November 2017, 30 HNC patients who underwent RT or CCRT were randomly allocated to receive either NS-21 or control treatment on their irradiated skin three times per day, starting at the initiation of RT or CCRT and ending 2 weeks after the completion of RT or until the appearance of grade 3 acute radiation dermatitis (ARD). Dermatitis was recorded weekly according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Skin humidity was monitored by a digital moisture meter. The generalized estimating equation (GEE) and logit link function method were used for statistical analysis., Results: No serious adverse events were observed in either group. Itching dermatitis occurred on the right lower neck in one patient of the NS-21 group during the 3rd week of CCRT, but the severity was mild. The median skin moisture value at the time of the final treatment was significantly different between the study and control groups (30.6 vs. 27.3, p = 0.013). Additionally, there was an inverse relationship between skin moisture and ARD grade (B = -0.04, p = 0.005). The incidence of ARD at the time of the last treatment was not significantly different between the study and control groups (6.7% vs 26.7%, p = 0.165). The risk of grade 3 ARD for skin that had received an irradiation dose of 47-70 Gy was higher than that of skin that had received an irradiation dose ≤46 Gy (OR = 31.06, 95% CI =5.95-162.21, p < 0.001). Nevertheless, the risk of ARD was not significantly different between the groups (OR = 0.38, 95% CI = 0.08-1.74, p = 0.212)., Conclusions: NS-21 was well tolerated and effective for the maintenance of skin moisture; however, there was no statistically significant reduction in the risk of ARD in HNC patients undergoing RT or CCRT when compared with HNC patients in the control group., Trial Registration: The study was approved by the Institutional Review Board of Far Eastern Memorial Hospital ( FEMH-IRB , 104048-F), Registered 1st June 2015.

Background: This study seeks to assess quality of life (QOL) and utility scores of head and neck cancer survivors., Methods: We compared QOL as indicated by EORTC QLQ-C30, QLQ-H&N35, utility scores by time trade off (TTO) with previous published reference values and tested series characteristics related to global QOL and utility., Results: A total of 127 patients were recruited. Of the patients, 102 (80%) completed the utility assessment. Cancer survivors had lower scores compared with norm values. Patients without a spouse had a lower utility than those with a spouse. Patients with a low annual family income also had lower global QOL and utility scores (p < 0.05). Other factors were not significantly related to QOL and utility scores., Conclusion: Disease and treatment of head and neck cancer lead to disability and poor health-related QOL and utility. Economic status may contribute to health-related QOL and utility, while marital status is related to utility for head and neck cancer patients.

Background: Helical irradiation of the total skin (HITS) was modified as simultaneous integrated boost (SIB)-helical arc radiotherapy of total skin (HEARTS) technique and applied to an acute myeloid leukemia (AML) patient with disseminated leukemia cutis., Methods: The original HITS plan was revised for different regimens, i.e. HEARTS, low-dose HEARTS and SIB-HEARTS. The uniformity index (UI), conformity index (CI), and dose of organs at risk (OARs) were used to evaluate the plans. Additionally, the SIB-HEART (21/15 Gy) was delivered to the total skin and chloromas., Results: No significant differences were observed for the CI and UI between HITS and HEARTS regimens. Compared with HITS, the reduced mean doses to various bone marrows ranged from 17 to 88%. The mean OARs doses for the head, chest and abdomen of a patient with AML treated with SIB-HEARTS (21/15 Gy) were 2.1 to 21.9 Gy, 1.8 to 7.8 Gy and 1.7 to 3.3 Gy, respectively. No severe adverse effects were noted except for grade 4 leukocytopenia and thrombocytopenia., Conclusion: HEARTS and different regimens reduced the dose to OARs and bone marrow while maintaining the uniformity and conformity. SIB-HEARTS deliveries different doses to the total skin and enlarged tumors simultaneously., Trial Registration: Retrospectively registered and approved by the Institutional Review Board of our hospital ( FEMH-106151-C ).

Background: The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self-expandable metal stents (SEMS) for the treatment of locally advanced esophageal cancer., Materials and Methods: Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty-eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed., Results: The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio [HR], 72.30; 95% confidence interval [CI], 8.62-606.12; p  < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15-15.21; p  < .001)., Conclusion: CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life-threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations., Implications for Practice: Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Because of the anatomical location, patients with head and neck cancer (HNC) frequently experience dysphagia and malnutrition at the time of diagnosis and these conditions are often exacerbated after chemoradiotherapy. There is an emerging medical need to establish a consensus on nutritional intervention for these patients. A panel of 30 senior physicians and experts from multidisciplinary teams drafted clinical recommendations to improve the management of nutritional interventions in Taiwan and to provide updated treatment strategy recommendations in hope of improving the nutritional status of patients with HNC. This clinical review describes the resulting consensus document, including the impact of malnutrition on clinical outcomes, the role of prophylactic tube feeding, the choice of tube feeding, and the benefit of oral nutritional supplements in patients with HNC undergoing chemoradiotherapy. The outcomes of this review will support clinicians in their efforts to improve the nutritional status of patients with HNC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To establish a real-time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation., Methods: One-hundred forty-four irradiation-treated patients underwent ultrasonography and ultrasound-guided fine-needle aspirations (USgFNAs), and the resultant data were used to construct a real-time and computerised predictive scoring model. This scoring system was further compared with our previously proposed prediction model., Results: A predictive scoring model, 1.35 × (L axis) + 2.03 × (S axis) + 2.27 × (margin) + 1.48 × (echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c-statistic) were 0.89 and 0.81, respectively (P < .05)., Conclusions: A real-time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation., (© 2017 John Wiley & Sons Ltd.)

Rationale: Nasopharyngeal carcinoma (NPC) has a high propensity of metastasis. The most commonly described sites of distant metastasis are the bones, lungs, and liver, whereas axillary metastasis is seldom reported., Patient Concerns: We hereby present the case of a 66-year-old man with NPC, cT2N2M0, at diagnosis. He had completed chemoradiotherapy and been disease-free for 7 years., Diagnoses: After that period, late recurrence in the form of a solitary axillary lymph node metastasis was detected and confirmed by core-needle biopsy., Interventions: The lesion was chemoresistant but responded to salvage radiotherapy at a dose of 65 Gy in 21 fractions., Outcomes: Post-radiotherapy positron emission tomography scan showed no evidence of disease., Lessons: We suggested that long-term follow-up of NPC patients is important because a late relapse may occur at an unusual site. Aggressive management of solitary metastasis may achieve good outcome.

Little is known about the clinical effects of shared medical decision making (SMDM) associated with quality of life about oral cancer? To understand patients who occurred potential cause of SMDM and extended to explore the interrelated components of quality of life for providing patients with potential adaptation of early assessment. All consenting patients completed the SMDM questionnaire and 36-Item Short Form (SF-36). Regression analyses were conducted to find predictors of quality of life among oral cancer patients. The proposed model predicted 57.4% of the variance in patients' SF-36 Mental Component scores. Patient mental component summary scores were associated with smoking habit (β=-0.3449, p=0.022), autonomy (β=-0.226, p=0.018) and Control preference (β=-0.388, p=0.007). The proposed model predicted 42.6% of the variance in patients' SF-36 Physical component scores. Patient physical component summary scores were associated with higher education (β=0.288, p=0.007), employment status (β=-0.225, p=0.033), involvement perceived (β=-0.606, p=0.011) and Risk communication (β=-0.558, p=0.019). Future research is necessary to determine whether oral cancer patients would benefit from early screening and intervention to address shared medical decision making.

Often, clinical decision making of reconstructive procedure is coupled and their concurrent resolution by interacting stakeholders is required. This study was to give new insight into the tradeoff method to elicit the utility function first and then the probability weighting function, to determine if and how stakeholder engagement can contribute to managing decisional conflict processes. The proposed methodology is illustrated through three subjects (physician, patient and family member). We found that significant evidence of probability weighting both at the aggregate level and at the individual subject level. The pattern of probability weights is consistent with an inverse shaped probability weighting function: Small probabilities are overweighed and intermediate and large probabilities are underweight. In addition, the degree of upper subadditivity exceeds the degree of lower subadditivity. Finally, the proposed procedure can reduce clinical risk by considering stakeholders' behavior attribute and providing physicians the effective support need for quality decision making.

Objectives: To investigate the effect of radiotherapy (RT) on ultrasound-guided fine needle aspiration (USgFNA) and sonographic characteristics in the assessment of cervical lymph nodes (LNs) in oral squamous cell carcinoma (OSCC) patients after primary treatment., Materials and Methods: 88 treated OSCC patients underwent 111 USgFNAs of the neck LNs after US evaluation. Among them, 48 USgFNAs were performed on 40 patients following RT and 63 USgFNAs on 48 patients without previous RT. The results of USgFNA and the US characteristics were compared between these two groups., Results: USgFNA had a sensitivity of 88.0%, specificity of 91.4%, positive predictive value (PPV) of 88.0%, negative predictive value (NPV) of 91.4% and accuracy of 90.0% in patients without previous RT, and a sensitivity of 97.1%, specificity of 83.3%, PPV of 94.3%, NPV of 90.9% and accuracy of 93.5% in those with previous neck RT. The ranges of the short-axis and long-axis length were 13.3 ± 8.0 mm (mean ± SD) versus 17.8 ± 9.1 mm, and 18.6 ± 9.0 mm versus 24.4 ± 10.9 mm for recurrent LNs from patients with, versus without, previous RT (both ps < 0.05), respectively. 76.5% (26/34) of the recurrent nodes after RT and 48% (12/25) of the recurrent nodes without previous RT exhibited an irregular margin (p < 0.05). Additionally, irradiated recurrent LNs had a significantly decreased percentage of discernable calcification compared with non-irradiated recurrent nodes (48% versus 20.6%, p < 0.05)., Conclusions: RT had influence on sonographic characteristics but no influence on USgFNA in diagnosing recurrent LNs in treated OSCC patients.

Background: We compared the outcome of patients who received non-image-guided intensity-modulated radiotherapy (IMRT) with those who received helical tomotherapy (HT), a daily image-guided radiotherapy (IGRT), after surgery for oral cavity cancer (OCC)., Methods: During the period November 2006 to December 2013, a total of 152 postoperative OCC patients underwent either IMRT (n = 79) or daily IGRT (n = 73) 4 to 6 weeks after surgery. Patients in the IMRT group received 6 MV photon beams to 7 fields and those in the IGRT group received daily fractions of 1.8 or 2 Gy on five consecutive days., Results: Patients who received daily IGRT had higher 5-year overall survival than those who received IMRT (87% versus 48%, p = 0.015). The local progression-free survival rate was also higher in patients who received IGRT (85% versus 58%, p = 0.006). More patients in the IGRT group completed the package of overall treatment time in ≤ 13 weeks and completed their course of radiation therapy in ≤ 8 weeks than patients in the IMRT group (89% versus 68%, p = 0.002; 84% versus 58%, p = 0.001), respectively. The rate of local failure in the primary tumor area was 24.0 % in the IMRT group and 6.8% in the IGRT group. Among patients with primary local failure, the marginal failure rate was 52.6% in the IMRT group and 0 % in the IGRT group., Conclusions: For patients with locally advanced OCC, postoperative IGRT results in better overall survival, better local progression-free survival, less marginal failure and shorter overall treatment time than postoperative non-image-guided IMRT.

Aortic pseudoaneurysm formation subsequent to concurrent chemoradiotherapy (CCRT) for esophageal cancer patient with esophageal metallic stent insertion is a rare condition.A 52-year-old man with esophageal cancer, cT4N1M0, stage IIIC, was treated with concurrent weekly cisplatin (30 mg/m) and 5-Fluorouracil (500 mg/m) as well as radiotherapy (50.4 Gy in 28 fractions) for 6 weeks. An esophageal metallic stent was inserted for dysphagia 1 week after initiation of CCRT. During the treatment regimen, the platelet count dropped to less than 200 × 10 /μL. One month after the completion of CCRT, chest CT revealed the presence of an aortic pseudoaneurysm as well as aortoesophageal fistulas. A thoracic aortic endografting was performed and the patient responded well to surgery. However, the patient died 2 months later due to a nosocomial infection.Multimodality treatment for esophageal cancer comprising cisplatin-based CCRT and esophageal metallic stent placement near a great vessel may increase the risk of pseudoaneurysm formation.

Radiation pneumonitis (RP) is a common complication for radiotherapy of esophageal cancer and is associated with the low dose irradiated lung volume. This study aims to reduce the mean lung dose (MLD) and the relative lung volume at 20 Gy (V 20) and at low dose region using various designs of the fan-shaped complete block (FSCB) in helical tomotherapy. Hypothetical esophageal tumor was delineated on an anthropomorphic phantom. The FSCB was defined as the fan-shaped radiation restricted area located in both lungs. Seven treatment plans were performed with nonblock design and FSCB with different fan angles, that is, from 90° to 140°, with increment of 10°. The homogeneous index, conformation number, MLD, and the relative lung volume receiving more than 5, 10, 15, and 20 Gy (V 5, V 10, V 15, and V 20) were determined for each treatment scheme. There was a substantial reduction in the MLD, V 5, V 10, V 15, and V 20 when using different types of FSCB as compared to the nonblock design. The reduction of V 20, V 15, V 10, and V 5 was 6.3%-8.6%, 16%-23%, 42%-57%, and 42%-66% for FSCB 90°-140°, respectively. The use of FSCB in helical tomotherapy is a promising method to reduce the MLD, V 20, and relative lung volume in low dose region, especially in V 5 and V 10 for esophageal cancer.

To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal-Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy.

Purpose: Limited-tomotherapy and hybrid-IMRT treatment techniques were compared for reductions in ipsilateral and contralateral lung, heart, and contralateral breast radiation doses., Methods and Materials: Thirty consecutively treated left-sided early-stage breast cancer patients were scheduled for lTomo and hIMRT. For the hIMRT plan conventional tangential-field and four-field IMRT plans were combined with different weightings in the prescribed dose. For the lTomo plan a geometrically limited arc was designed for the beamlet entrance. A D p of 50.4 Gy in 28 fractions was used for the PTV. The dose coverage, homogeneity index, conformity index of the target, and the dose volumes of critical structures were compared., Results: Both modalities presented similar target coverage. The homogeneity and conformity were improved for lTomo with P < 0.001 and P = 0.006, respectively. In the lTomo plan a concave dose distribution was generated with significant dose reductions in both high and low dose regions for ipsilateral lung and heart (P < 0.001). Conclusions. lTomo plan can have similar dose coverage and better homogeneity and conformity to the target. By properly designing the directionally and completely blocked structure, lTomo plan was developed successfully in reducing doses to the healthy tissues for early-stage left-sided breast cancer radiotherapy.

Background: The prevalence of esophageal neoplasia in head and neck (H&N) cancer patients is not low; however, routine esophageal surveillance is not included in staging of newly-diagnosed H&N cancers. We aimed to investigate the risk factors for synchronous esophageal neoplasia and the impact of endoscopy on management of H&N cancer patients., Methods: A total of 129 newly diagnosed H&N cancer patients who underwent endoscopy with white-light imaging, narrow-band imaging (NBI) with magnifying endoscopy (ME), and chromoendoscopy with 1.5% Lugol's solution, before definite treatment were enrolled prospectively., Results: 60 esophageal lesions were biopsied from 53 (41.1%) patients, including 11 low-grade, 14 high-grade intraepithelial neoplasia and 12 invasive carcinoma in 30 (23.3%) patients. Alcohol consumption [odds ratio (OR) 5.90, 95% confidence interval (CI) 1.23-26.44], advanced stage (stage III and IV) of index H&N cancers (OR 2.98, 95% CI 1.11-7.99), and lower body mass index (BMI) (every 1-kg/m2 increment with OR 0.87, 95% CI 0.76-0.99) were independent risk factors for synchronous esophageal neoplasia. NBI with ME was the ideal screening tool (sensitivity, specificity, and accuracy of 97.3%, 94.1%, and 96.3%, respectively, for detection of dysplastic and cancerous esophageal lesions). The treatment strategy was modified after endoscopy in 20 (15.5%) patients. The number needed to screen was 6.45 (95% CI 4.60-10.90)., Conclusions: NBI-ME surveillance of esophagus should be done in newly-diagnosed H&N cancer patients, especially those with alcohol drinking, lower BMI, and advanced stage of primary tumor.

A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS) and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB) technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

To compare the outcomes of melphalan 200 mg/m² (HDM200) and 8 Gy total marrow irradiation (TMI) delivered by helical tomotherapy plus melphalan 140 mg/m² (HDM140 + TMI 8 Gy) in newly diagnosed symptomatic multiple myeloma (MM) Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT) were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD) regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP). In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P = 0.048). However, hematologic recovery (except for neutrophils), transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P = 0.387). As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200.

An anthropomorphic phantom was used to investigate a treatment technique and analyze the dose distributions for helical irradiation of the total skin (HITS) by helical tomotherapy (HT). Hypothetical bolus of thicknesses of 0, 10, and 15 mm was added around the phantom body to account for the dose homogeneity and setup uncertainty. A central core structure was assigned as a "complete block" to force the dose tangential delivery. HITS technique with prescribed dose (D p ) of 36 Gy in 36 fractions was generated. The radiochromic EBT2 films were used for the dose measurements. The target region with 95.0% of the D p received by more than 95% of the PTV was obtained. The calculated mean doses for the organs at risk (OARs) were 4.69, 3.10, 3.20, and 2.94 Gy for the lung, heart, liver, and kidneys, respectively. The measurement doses on a phantom surface for a plan with 10 mm hypothetical bolus and bolus thicknesses of 0, 1, 2, and 3 mm are 89.5%, 111.4%, 116.9%, and 117.7% of D p , respectively. HITS can provide an accurate and uniform treatment dose in the skin with limited doses to OARs and is safe to replace a total skin electron beam regimen.

In patients given postmastectomy radiotherapy (PMRT), the chest wall is a very thin layer of soft tissue with a low-density lung tissue behind. Chest wall treated in this situation with a high-energy photon beam presents a high dosimetric uncertainty region for both calculation and measurement. The purpose of this study was to measure and to evaluate the surface and superficial doses for patients requiring PMRT with different treatment techniques. An elliptic cylinder cork and superflab boluses were used to simulate the lung and the chest wall, respectively. Sets of computed tomography (CT) images with different chest wall thicknesses were acquired for the study phantom. Hypothetical clinical target volumes (CTVs) were outlined and modified to fit a margin of 1-3 mm, depending on the chest wall thickness, away from the surface for the sets of CT images. The planning target volume (PTV) was initially created by expanding an isotropic 3-mm margin from the CTV, and then a margin of 3 mm was shrunk from the phantom surface to avoid artifact-driven results in the beam-let intensity. Treatment techniques using a pair of tangential wedged fields (TWFs) and 4-field intensity-modulated radiation therapy (IMRT) were designed with a prescribed fraction dose (D(p)) of 180 cGy. Superficial dose profiles around the phantom circumference at depths of 0, 1, 2, 3, and 5 mm were obtained for each treatment technique using radiochromic external beam therapy (EBT) films. EBT film exhibits good characteristics for dose measurements in the buildup region. Underdoses at the median and lateral regions of the TWF plans were shown. The dose profiles at shallow depths for the TWF plans show a dose buildup about 3 mm at the median and lateral tangential incident regions with a surface dose of about 52% of D(p). The dose was gradually increased toward the most obliquely tangential angle with a maximum dose of about 118% of D(p.) Dose profiles were more uniform in the PTV region for the 4-F IMRT plans. Most of the PTV region had doses >94% of D(p) at depths >1 mm. The mean surface dose was about 65% of D(p) for the 4-F IMRT plans. The maximum dose for the 4-F IMRT plans was <118.4% of D(p). The application of added bolus has to consider the treatment technique, tumor coverage, and possible skin reactions. For PMRT, if the chest surface and wall are treated adequately, at least 3 mm bolus should be added to the chest wall when tangential beams and 6-MV photon energy are arranged. However, when the surface and superficial regions are not high-risk areas, an IMRT plan with tangential beams and 6-MV photon energy can provide uniform dose distributions within the PTV, spare the skin reaction, and deliver sufficient doses to the chest wall at depths >1 mm., (Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Malignant melanoma of the uterine cervix is a rare extracutaneous melanoma which develops aggressively and is associated with a bleak prognosis. To our knowledge, no prior published reports have discussed the role of 18F-FDG positron emission tomography/computed tomography (PET/CT) in managing this disease. Our case study involved a 66-year-old woman with a malignant melanoma of the uterine cervix. The patient received PET/CT that identified metastases and lesions which had not been detected from her MRI. Serial PET/CT elucidated that the disease was initially limited to the pelvis, but then metastasized to the abdominal para-aortic lymph nodes, followed by extensive metastases to the brain, lungs, breast, supraclavicular, neck, and other abdominal lymph nodes, as observed at 6-month follow-up. PET/CT was used to complement conventional anatomic imaging modalities, and provided a novel modality for whole body screening. Visualization of the metabolic activity of indeterminate lesions may help in staging, re-staging, treatment planning, and prognostic prediction for patients with this rare disease.

Background: To examine the effects of norcantharidin (NCTD) on development of human myeloid dendritic cells (DCs) in vitro and in skin allograft transplantation in vivo., Methods: Human CD14(+) monocytes were isolated and triggered differentiation and maturation toward myeloid DCs with and without NCTD. The cell morphology, viability, cell death, expression of surface markers and co-stimulatory molecules, allostimulatory activity, and cytokine production were examined for characterization of DCs. The rejection of mice skin allograft model was used to translate the in vitro effect of cantharidin (CTD) and NCTD on DCs., Results: DCs developed in the presence of NCTD showed decreased viability, cell death with necrosis, and lower expression of CD1a and CD83. DCs triggered in the presence of NCTD possessed a greater allostimulatory activity in naive CD4(+)CD45RA(+) T cells. NCTD modulated DCs through calcineurin phosphatase but not through mammalian target of rapamycin or downstream molecule p70S6 kinase. In vivo, NCTD caused accumulation and co-localization of antigen-presenting cells and regulatory T cells in the interfollicular area of the recipients' spleens. CTD and NCTD prolonged skin allograft survival along with less severe histopathological inflammatory reactions. CTD, but not NCTD, treatment caused elevation of serum alanine aminotransferase and evident mortality of the recipients., Conclusion: NCTD modulated the differentiation and maturation of human myeloid DCs and caused deviation of standard DC differentiation toward a tolerogenic phenotype through calcineurin phosphatase inhibition. In vivo, both drugs effectively prolonged skin allograft survival. NCTD was less toxic than CTD, and thus, has potential for development as an immunosuppressant for transplant rejection.

Background: To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC)., Methods: Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction., Results: After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively., Conclusion: HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings.

Background: To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer., Methods: From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison., Results: The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% vs .37.5%, respectively; the corresponding values for disease-free survival were 58.3% vs. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% vs. 83.3%, respectively; and for metastases-free survival, the values were 66.7% vs. 60.0%, respectively. The 2-year OS rates for T1, 2 vs. T3, 4 were 66.7% vs. 35.4%, respectively (p = 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, p = 0.004)., Conclusion: IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate.

Purpose: Dosimetric uncertainty in the surface and superficial regions is still a major concern for radiation therapy and becomes more important when using the inverse planning algorithm for IMRT. The purpose of this study was to measure dose distributions and to evaluate the calculation accuracy in the superficial region for different planning target volume (PTV) shrinkage methods for head and neck IMRT plans., Methods: A spherical polystyrene phantom 160 mm in diameter (ball phantom) was used to simulate the shape of the head. Strips of superflab bolus with thicknesses of 3.5 and 7.0 mm were spread on the surface of the ball phantom. Three sets of CT images were acquired for the ball phantom without and with the bolus. The hypothetical clinical target volume (CTV) and critical structures (spinal cord and parotid glands) were outlined on each set of CT images. The PTVs were initially created by expanding an isotropic 3 mm margin from the CTV and then margins of 0, 3, and 5 mm were shrunk from the phantom surface for dosimetric analysis. Seven-field IMRT plans with a prescribed dose of 180 cGy and same dose constraints were designed using an Eclipse treatment planning system. Superficial doses at depths of 0, 3.5, and 7.0 mm and at seven beam axis positions (gantry angles of 0 degrees, 30 degrees, 60 degrees, 80 degrees, 330 degrees, 300 degrees, and 280 degrees) were measured for each PTV shrinkage margin using 0.1 mm ultrathin thermoluminescent dosimeters. For each plan, the measured doses were compared to the calculated doses., Results: The PTV without shrinkage had the highest intensity and the steepest dose gradient in the superficial region. The mean measured doses for different positions at depths of 0, 3.5, and 7.0 mm were 106 +/- 18, 185 +/- 16, and 188 +/- 12 cGy, respectively. For a PTV with 3 mm shrinkage, the mean measured doses were 94 +/- 13, 183 +/- 8, and 191 +/- 8 cGy. For a PTV with 5 mm shrinkage, the mean measured doses were 86 +/- 11, 173 +/- 8, and 187 +/- 5 cGy. The comparisons indicated that more than 73.3% of the calculated points are with doses lower than the measured points and the difference of the dose becomes more significant in the shallower region. At 7.0 mm depth, the average difference between calculations and measurements was 2.5% (maximum 5.5%)., Conclusions: Application of the PTV shrinkage method should take into account the calculation inaccuracy, tumor coverage, and possible skin reaction. When the tumor does not invade the superficial region, an adequate shrinkage margin from the surface is helpful for reducing the skin reaction. As the tumor invades the superficial region, adding a bolus is a method better than only contouring PTV with skin inclusion.

Background: The aim of this study was to assess the treatment results and toxicity profiles of helical tomotherapy (HT) for postoperative high-risk oral cavity cancer., Methods: From December 6, 2006 through October 9, 2009, 19 postoperative high-risk oral cavity cancer patients were enrolled. All of the patients received HT with (84%) or without (16%) chemotherapy., Results: The median follow-up time was 17 months. The 2-year overall survival, disease-free survival, locoregional control, and distant metastasis-free rates were 94%, 84%, 92%, and 94%, respectively. The package of overall treatment time > 13 wk, the interval between surgery and radiation ≤ 6 wk, and the overall treatment time of radiation ≤ 7 wk was 21%, 84%, and 79%, respectively. The percentage of grade 3 mucositis, dermatitis, and leucopenia was 42%, 5% and 5%, respectively., Conclusions: HT achieved encouraging clinical outcomes for postoperative high-risk oral cavity cancer patients with high compliance. A long-term follow-up study is needed to confirm these preliminary findings.

Background: Stereotactic body radiation therapy (SBRT) applied by helical tomotherapy (HT) is feasible for lung cancer in clinical. Using SBRT concurrently with erlotinib for non-small cell lung cancer (NSCLC) is not reported previously., Case Presentation: A 77-year-old man with stage III NSCLC, received erlotinib 150 mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9 fractions was delivered to the tumor bed. The tumor responded dramatically and the combined regimen was well tolerated. After concurrent erlotinib-SBRT, erlotinib was continued as maintenance therapy. The patient developed dyspnea three months after the combined therapy and radiation pneumonitis with interstitial lung disease was suspected., Conclusions: Combination SBRT, HT, and erlotinib therapy provided effective anti-tumor results. Nonetheless, the potential risks of enhanced adverse effects between radiation and erlotinib should be monitored closely, especially when SBRT is part of the regimen.

Background: Stereotactic body radiation therapy (SBRT) administered via a helical tomotherapy (HT) system is an effective modality for treating lung cancer and metastatic liver tumors. Whether SBRT delivered via HT is a feasible alternative to brachytherapy in treatment of locally advanced cervical cancer in patients with unusual anatomic configurations of the uterus has never been studied., Case Presentation: A 46-year-old woman presented with an 8-month history of abnormal vaginal bleeding. Biopsy revealed squamous cell carcinoma of the cervix. Magnetic resonance imaging (MRI) showed a cervical tumor with direct invasion of the right parametrium, bilateral hydronephrosis, and multiple uterine myomas. International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer was diagnosed. Concurrent chemoradiation therapy (CCRT) followed by SBRT delivered via HT was administered instead of brachytherapy because of the presence of multiple uterine myomas with bleeding tendency. Total abdominal hysterectomy was performed after 6 weeks of treatment because of the presence of multiple uterine myomas. Neither pelvic MRI nor results of histopathologic examination at X-month follow-up showed evidence of tumor recurrence. Only grade 1 nausea and vomiting during treatment were noted. Lower gastrointestinal bleeding was noted at 14-month follow-up. No fistula formation and no evidence of haematological, gastrointestinal or genitourinary toxicities were noted on the most recent follow-up., Conclusions: CCRT followed by SBRT appears to be an effective and safe modality for treatment of cervical cancer. Larger-scale studies are warranted.

Purpose: To review the experience with and evaluate the treatment plan for helical tomotherapy for the treatment of oropharyngeal cancer., Methods and Materials: Between November 1, 2006 and January 31, 2009, 10 histologically confirmed oropharyngeal cancer patients were enrolled. All patients received definitive concurrent chemoradiation with helical tomotherapy. The prescription dose to the gross tumor planning target volume, the high-risk subclinical area, and the low-risk subclinical area was 70 Gy, 63 Gy, and 56 Gy, respectively. During radiotherapy, all patients were treated with cisplatin, 30 mg/m(2), plus 5-fluorouracil (425 mg/m(2))/leucovorin (30 mg/m(2)) intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. Several parameters, including maximal or median dose to critical organs, uniformity index, and conformal index, were evaluated from dose-volume histograms., Results: The mean survival was 18 months (range, 7-22 months). The actuarial overall survival, disease-free survival, locoregional control, and distant metastasis-free rates at 18 months were 67%, 70%, 80%, and 100%, respectively. The average for uniformity index and conformal index was 1.05 and 1.26, respectively. The mean of median dose for right side and left side parotid glands was 23.5 and 23.9 Gy, respectively. No Grade 3 toxicity for dermatitis and body weight loss and only one instance of Grade 3 mucositis were noted., Conclusion: Helical tomotherapy achieved encouraging clinical outcomes in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable, even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings., ((c) 2010 Elsevier Inc. All rights reserved.)

Background: To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT)., Methods: Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46-54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30<30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram., Results: HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively., Conclusion: Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.