Epidemiology of Aspergillosis in Cancer Patients in Taiwan.

Purpose: The incidence of aspergillosis is increasing, and the risk factors for infection include cancer, admission to the intensive care unit, chronic pulmonary diseases, immunocompromised status, and taking immunomodulatory drugs. There are limited data about the incidence of aspergillosis in patients with different types of cancer. The aim of our study was to survey the incidence of aspergillosis in different cancer types from 2006 to 2017. Patients and Methods: Data were collected from the Taiwan Cancer Registry database and International Classification of Diseases, 9th, 10th Revision, and Clinical Modification codes for diagnosing aspergillosis. Patients with a history of aspergillosis before cancer were excluded, and the secondary outcome was the risk of mortality in cancer patients with and without aspergillosis after 1 year. Results: Among 951 cancer patients with a diagnosis of aspergillosis, there were 614 hematopoietic and reticuloendothelial system patients, 100 lung cancer patients, and 73 lymphoma cancer patients. The overall incidence rates of aspergillosis tended to increase significantly from 2006 to 2017 (from 3.50 to 13.37 per 10,000 person-years, p value: <0.0001). Regarding sex, the incidence rates of aspergillosis in males and females were 12.52 and 7.53 per 10,000 person-years, respectively. Patients with a diagnosis of aspergillosis had a 2.30-fold (95% CI: 2.14-2.48, p value: <0.0001) higher risk of mortality than those without aspergillosis. Conclusion: The incidence of aspergillosis was increased in cancer patients, and cancer patients with aspergillosis had a significantly higher risk of mortality than those without aspergillosis.

IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma.

Predicting and overcoming radioresistance are crucial in radiation oncology, including in managing oral squamous cell carcinoma (OSCC). First, we used RNA-sequence to compare expression profiles of parent OML1 and radioresistant OML1-R OSCC cells in order to select candidate genes responsible for radiation sensitivity. We identified IRAK2, a key immune mediator of the IL-1R/TLR signaling, as a potential target in investigating radiosensitivity. In four OSCC cell lines, we observed that intrinsically low IRAK2 expression demonstrated a radioresistant phenotype (i.e., OML1-R and SCC4), and vice versa (i.e., OML1 and SCC25). Next, we overexpressed IRAK2 in low IRAK2-expression OSCC cells and knocked it down in high IRAK2-expression cells to examine changes of irradiation response. After ionizing radiation (IR) exposure, IRAK2 overexpression enhanced the radiosensitivity of radioresistant cells and synergistically suppressed OSCC cell growth both in vitro and in vivo, and vice versa. We found that IRAK2 overexpression restored and enhanced radiosensitivity by enhancing IR-induced cell killing via caspase-8/3-dependent apoptosis. OSCC patients with high IRAK2 expression had better post-irradiation local control than those with low expression (i.e., 87.4% vs. 60.0% at five years, P = 0.055), showing that IRAK2 expression was associated with post-radiation recurrence. Multivariate analysis confirmed high IRAK2 expression as an independent predictor for local control (HR, 0.11; 95% CI, 0.016 - 0.760; P = 0.025). In conclusion, IRAK2 enhances radiosensitivity, via modulating caspase 8/3-medicated apoptosis, potentially playing double roles as a predictive biomarker and a novel therapeutic target in OSCC.

Macrophage migration inhibitory factor regulates integrin-ß1 and cyclin D1 expression via ERK pathway in podocytes.

AIMS: Macrophage migration inhibitory factor (MIF) is found to increase in proliferative glomerulonephritis. MIF binds to the MIF receptor (CD74) that activates MAP kinase (ERK and p38). Integrins and cyclinD1 regulate cell proliferation, differentiation and adhesion. This study evaluates whether MIF can regulate integrin-ß1/cyclin D1 expression and cell adhesion of podocytes. MAIN METHODS: Expression of integrin-ß1 mRNA/protein and cyclin D1 mRNA under stimulation of MIF was evaluated by real-time PCR and Western blotting. MIF receptor (CD74) and MAP kinase under MIF treatment were examined to determine which pathway regulated integrin-ß1 and cyclin D1 expression. Cell adhesion was evaluated under MIF treatment and/or anti-integrin-ß1 antibody by cell adhesion assay. KEY FINDINGS: Protein levels of integrin-ß1 were up-regulated under MIF treatment in a dosage-dependent manner. CD74 protein levels were not changed after MIF treatment. Integrin-ß1 and cyclin D1 mRNA levels were up-regulated after MIF 100 ng/ml treatment. ERK inhibitor U0126 reduced MIF-induced the increase in integrin-ß1 mRNA and protein expression following MIF stimulation. However, p38 inhibitor SB 203580 did not inhibit MIF-induced increase in integrin-ß1 mRNA and protein expression following MIF stimulation. MIF-induced increase in cyclin D1 mRNA level also was inhibited only by U0126 following MIF stimulation. Podocyte adhesion was increased after MIF treatment, but, anti-integrin-ß1 antibody decreased MIF-enhanced podocyte adhesion. SIGNIFICANCE: MIF increases integrin-ß1 and cyclin D1 expression through the ERK pathway in podocytes, and the up-regulated expression of integrin-ß1 increases podocyte adhesion. These results provide further understanding for the role of MIF in developing proliferative glomerulonephritis.

Oligo(ethylene glycol) side chain effect on the physical properties and molecular arrangement of oligothiophene-isoindigo based conjugated polymers.

Oligo(ethylene glycol) (OEG) side chains are widely used in donor-acceptor conjugated polymers (D-A CPs) and enable the polymers to dissolve and be processed in environmentally friendly and cost-effective nonchlorinated solvents, such as water. However, the OEG effect on the physical properties of D-A CPs has not been thoroughly studied and sometimes the results are controversial. In this study, two oligothiophene-isoindigo based conjugated polymers, P3TI and P4TI, are selected as model polymers to investigate the OEG effect. PnTI has octyl side chains on the oligothiophene unit and 2-hexyldecyl side chains on the isoindigo unit. The replacement of an alkyl side chain with OEG not only changes the optical and thermal properties but also the molecular arrangements of the polymers such as π-π d-spacing, crystallinity, and packing orientation. The domination of the crystallization behavior changes from the oligothiophene unit to the isoindigo unit when the bulky alkyl group is replaced by the flexible and linear OEG. The packing changes from edge-on to face-on orientation. The results are intriguing and provide new insights into this class of polymers.

Moscatilin Inhibits Growth of Human Esophageal Cancer Xenograft and Sensitizes Cancer Cells to Radiotherapy.

Esophageal cancer prognosis remains poor in current clinical practice. We previously reported that moscatilin can induce apoptosis and mitotic catastrophe in esophageal cancer cells, accompanied by upregulation of polo-like kinase 1 (Plk1) expression. We aimed to validate in vitro activity and Plk1 expression in vivo following moscatilin treatment and to examine the treatment's radiosensitizing effect. Human esophageal cancer cells were implanted in nude mice. Moscatilin was intraperitoneally (i.p.) injected into the mice. Tumor size, body weight, white blood cell counts, and liver and renal function were measured. Aberrant mitosis and Plk1 expression were assessed. Colony formation was used to measure survival fraction after radiation. Moscatilin significantly suppressed tumor growth in mice bearing human esophageal xenografts without affecting body weight, white blood cell counts, or liver and renal function. Moscatilin also induced aberrant mitosis and apoptosis. Plk1 expression was markedly upregulated in vivo. Moreover, moscatilin pretreatment enhanced CE81T/VGH and BE3 cell radioresponse in vitro. Moscatilin may inhibit growth of human esophageal tumors and sensitize esophageal cancer cells to radiation therapy.

Andrographolide enhances the anti-metastatic effect of radiation in Ras-transformed cells via suppression of ERK-mediated MMP-2 activity.

BACKGROUND: Activation of Ras oncogene in human tumors is associated with radiation-associated metastatic potential. Although ionizing radiation is one important method of cancer treatments, it has been shown to enhance matrix metalloproteinases (MMPs) activity and facilitates a more aggressive cancer phenotype. Our previous studies showed that andrographolide with lower dose rates of radiation could inhibit RAS-transformed cancer metastasis in vivo; however, the molecular mechanisms are not yet clear. In this study, we aimed to explore the anti-metastatic effect of andrographolide combined with radiation on Ras-transformed cells. METHODS: RAS-transformed cells were treated with andrographolide in the presence or absence of irradiation (2-4 Gy) or angiotensin II to examine cell invasion. In vivo tumorigenesis assays were also performed. The MMP-2 activity was detected by using Gelatin zymography. Signal transduction of NF-κB subunit, p65 and phosphor-ERK 1/2, were examined by using Western blotting analysis. RESULTS: Treatment with andrographolide inhibited migration of Ras-transformed cells. Andrographolide treatment with radiation significantly inhibited cancer metastasis in vivo. We found that andrographolide exhibited anti-migration and anti-invasive ability against cancer metastasis via inhibition of MMP2 activity rather than affected MMP-9 and EMT. In addition, combined andrographolide with radiation appeared to be more effective in reducing MMP-2 expression, and this effect was accompanied by suppression of ERK activation that inhibits cancer cell migration and invasion. CONCLUSIONS: These findings suggest that andrographolide enhances the anti-metastatic effect of radiation in Ras-transformed cells via suppression of ERK-mediated MMP-2 activity.

Rice protein prolamin promotes anti-leukemia immunity and inhibits leukemia growth in vivo.

Prolamin is a heat-stable storage protein of rice (Oryza sativa). This study aimed to examine the effect of prolamin on anti-tumor immune response in vitro and leukemia growth in vivo. The prolamin-enriched rice fractions were prepared to stimulate peripheral blood mononuclear cells (MNC) from mice spleen. The MNC-conditioned medium (MNC-CM) was collected to treat leukemia L1210 cells. Human MNC-CM was prepared to treat Jurkat acute T cell leukemia cells. Purified prolamin was orally administered to syngeneic L1210-bearing DBA/2 mice to assess weights of tumor, liver and spleen, liver histopathology, peripheral blood neutrophil count and cytokine levels. Prolamin-prepared MNC-CM inhibited the viability of murine leukemia L1210 cells and human leukemia Jurkat cells, indicating an immunomodulatory effect. In syngeneic L1210-bearing DBA/2 mice, oral administration of purified prolamin dose-dependently decreased the tumor weight and attenuated the leukemia-induced reduction of liver and spleen weights. Prolamin inhibited the increase of peripheral blood leukocyte count. The levels of tumor necrosis factor-α and interferon-γ in MNC-CM and mice serum were significantly increased by prolamin treatment. No significant change in body weight, serum alanine aminotransferase and creatinine levels was noted by prolamin treatment. Rice prolamin could effectively promote anti-tumor immunity and inhibit leukemia growth without significant toxicity.

Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens.

OBJECTIVE: Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. METHODS: Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3-6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. RESULTS: A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3-5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). CONCLUSION: Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age.

Daphnoretin modulates differentiation and maturation of human dendritic cells through down-regulation of c-Jun N-terminal kinase.

Daphnoretin, an active constituent of Wikstroemia indica C.A. Meys, has been shown possessing anti-cancer activity. In this study, we examined the effect of daphnoretin on differentiation and maturation of human myeloid dendritic cells (DCs). After treatment with daphnoretin (0, 1.1, 3.3, 10 and 30µM) to initiate monocytes, the recovery rate of DCs was reduced in a dose-dependent manner. The mature DCs differentiated in the presence of daphnoretin had fewer and shorter dendrites. Daphnoretin modulated DCs differentiation and maturation in terms of lower expression of CD1a, CD40, CD83, DC-SIGN, and HLA-DR. Daphnoretin inhibited the allostimulatory activity of DCs on proliferation of naive CD4+CD45+RA+ T cell. On the mitogen-activated protein kinase, daphnoretin down-regulated the lipopolysaccharide-augmented expression of phosphorylated c-Jun N-terminal kinase (pJNK), but not p38 and extracellular signal-regulated kinase 1/2 (ERK1/2). Activation of JNK by anisomycin reversed the effect of daphnoretin on daphnoretin-inhibited pJNK expression and dendrite formation of DCs. In disease model related to maturation of DCs, daphnoretin suppressed the acute rejection of skin allografts in mice. Our results suggest that daphnoretin modulated differentiation and maturation of DCs toward a state of atypical maturation with impaired allostimulatory function and this effect may go through down-regulation of phosphorylated JNK.

Pelvic inflammatory disease increases the risk of a second primary malignancy in patients with cervical cancer treated by surgery alone.

As the number of long-term cervical cancer survivors continues to increase because of improvements in treatment, concerns about second primary malignancy have grown. The high-risk area of second primary cancers in cervical cancer survivors is the pelvis. Pelvic inflammatory disease (PID) could be a useful marker for gynecological cancers. Thus, we designed a large-scale, nationwide, controlled cohort study to investigate whether PID or other risk factors increased the risk of second primary cancers in patients with cervical cancer treated by surgery alone.Between 2000 and 2010, a total of 24,444 cervical cancer patients were identified using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan. Patients who received definite surgery were selected. To exclude the effect on second primary malignancy by treatment modalities, all cervical patients who ever having received adjuvant or definite radiotherapy or chemotherapy for primary cervical cancer were excluded. Finally, 3860 cervical cancer patients treated by surgery alone without adjuvant treatments were analyzed.Cox proportional hazards model was used for multivariate analysis and the Kaplan-Meier method was used to assess the cumulative risks. Regarding the incidence of second primary cancers, the standardized incidence ratio (SIR) was used.The median follow-up time was 56.6 months. The 6-year cumulative risk of second primary cancers is 0.16% and 0.12% for PID and without PID, respectively. After adjustment for confounders, age of less than 50 years, the presence of diabetes mellitus, and PID were significantly positivity associated with the risk of second primary cancers. The hazard ratios (HRs) of age less than 50 years, diabetes mellitus, and PID were 1.38 (95% CI = 1.11-2.04), 1.40 (95% CI = 1.06-1.85), and 1.35 (95% CI = 1.00-1.81), respectively. A higher incidence of second primary cancers was observed in the genitals, bladder, and colon.In conclusion, the incidence of second primary cancers was higher in the genitals, bladder, and colon in patients with cervical cancer treated with surgery alone. The patients with PID had a higher risk of second primary cancers.

Serum ferritin is an independent factor in coronary artery stenosis among hemodialysis patients.

Hemodialysis patients frequently receive intravenous iron for the treatment of anemia. Iron status has been found to be correlated with coronary artery disease. In the post hoc study reported here, we evaluate the association between iron status and coronary arterial stenosis (CAS) in a 3-year follow-up period. We enrolled 76 patients and collected iron status, and clinical/biochemical data over 3 years. In this study, coronary arterial stenosis was considered significant when the narrowing of the coronary artery exceeded 50 % of the luminal diameter on coronary angiography. The mean age was 61 years old. The female/male ratio was 48/28, and the group included 16 diabetic patients and 23 smokers. Twenty-two of 76 patients had CAS. Mean intravenous iron dosage was 2167.11 ± 1738.38 in a 3-year period. On the univariate regression analysis, 3-year-averaged serum ferritin was positively associated with CAS (r = 0.288, P = 0.012). The 3-year-averaged intravenous iron dosage, DM, age, smoking, and other biochemical parameters showed no association with CAS. When these factors were added to the multivariate-adjusted models, 3-year-averaged serum ferritin remained a determinant of CAS event (ß = 0.290, P = 0.029). The odds ratio for CAS was 6.93 (95 % CI 2.41-19.94; P = 0.001) for patients with 3-year-averaged serum ferritin ≥600 ng/mL. In summary, serum ferritin was an independent risk factor for CAS among this group of hemodialysis patients, especially when serum ferritin was ≥600 ng/mL.

Preliminary results of a non-invasive method to measure tumor size and distribution in vivo.

Molecular imaging of reporter gene expression in cancer cells can provide rapid, sensitive and non-invasive monitoring of tumor behavior. The aim of the present study was to establish a non-invasive method to measure tumor size and distribution in vivo. Briefly, H-Ras-transformed cells were stably transfected with a plasmid containing the luciferase gene (Luc), designated as Ras/Luc. Ras/Luc cells were injected into the back or tail vein of nude BALB/cAnN-Foxn1nu/CrlNarl mice (age, 6-8 weeks). Mice were subsequently administered D-luciferin via intra-peritoneal injection, prior to image acquisition. Photons emitted from the mice were detected via an imaging system. Tumor size and distribution in vivo were quantified as photons/second. Andrographolide has demonstrated radiosensitization in previous in vitro and in vivo studies. In the present study, the potential effects of andrographolide cancer metastasis were investigated further, using an imaging system. Preliminary results of andrographolide combined with radiation indicated the inhibition of cancer metastasis. The present mechanistic study of andrographolide-mediated effects demonstrated that activated extracellular signal regulated kinase protein and H2O2 production levels were significantly increased by andrographolide. In summary, the present study established a non-invasive method to measure tumor size and distribution in vivo and indicated that andrographolide may be a potential therapeutic strategy in cancer therapy.

Multiple target drug cocktail design for attacking the core network markers of four cancers using ligand-based and structure-based virtual screening methods.

BACKGROUND: Computer-aided drug design has a long history of being applied to discover new molecules to treat various cancers, but it has always been focused on single targets. The development of systems biology has let scientists reveal more hidden mechanisms of cancers, but attempts to apply systems biology to cancer therapies remain at preliminary stages. Our lab has successfully developed various systems biology models for several cancers. Based on these achievements, we present the first attempt to combine multiple-target therapy with systems biology. METHODS: In our previous study, we identified 28 significant proteins--i.e., common core network markers--of four types of cancers as house-keeping proteins of these cancers. In this study, we ranked these proteins by summing their carcinogenesis relevance values (CRVs) across the four cancers, and then performed docking and pharmacophore modeling to do virtual screening on the NCI database for anti-cancer drugs. We also performed pathway analysis on these proteins using Panther and MetaCore to reveal more mechanisms of these cancer house-keeping proteins. RESULTS: We designed several approaches to discover targets for multiple-target cocktail therapies. In the first one, we identified the top 20 drugs for each of the 28 cancer house-keeping proteins, and analyzed the docking pose to further understand the interaction mechanisms of these drugs. After screening for duplicates, we found that 13 of these drugs could target 11 proteins simultaneously. In the second approach, we chose the top 5 proteins with the highest summed CRVs and used them as the drug targets. We built a pharmacophore and applied it to do virtual screening against the Life-Chemical library for anti-cancer drugs. Based on these results, wet-lab bio-scientists could freely investigate combinations of these drugs for multiple-target therapy for cancers, in contrast to the traditional single target therapy. CONCLUSIONS: Combination of systems biology with computer-aided drug design could help us develop novel drug cocktails with multiple targets. We believe this will enhance the efficiency of therapeutic practice and lead to new directions for cancer therapy.

Anti-platelet factor 4/heparin antibody is associated with progression of peripheral arterial disease in hemodialysis patients.

BACKGROUND: Heparin therapy may induce anti-platelet factor 4/heparin antibody (PF4-H Ab). Hemodialysis patients receive scheduled heparin and are at a risk of developing PF4-H Ab. Hemodialysis patients are also at a high risk of peripheral arterial disease (PAD). This study examines whether chronic PF4-H Ab exposure contributes to the progression of PAD measured by ankle brachial index (ABI) in hemodialysis patients. MATERIALS AND METHODS: A total of 71 hemodialysis patients were enrolled, and the association between clinical, biochemical parameters and ABI after 3 years was studied. PF4-H Ab was evaluated by ELISA, and patients with titer ≥ 0.4 were taken as having PF4-H Ab. RESULTS: Mean ABI was 1.04 ± 0.18 at baseline and 1.01 ± 0.17 after 3 years. Mean ΔABI (change in ABI after 3 years) was -0.04 ± 0.13. PF4-H Ab was positive in 26 patients. PF4-H Ab was not related to hemodialysis duration, DM history, smoking and age. Platelet count showed no correlation with PF4-H Ab. However, there was significance in ΔABI between PF4-H Ab-positive and PF4-H Ab-negative patients (p = 0.002). ΔABI was negatively correlated with PF4-H Ab and 3-year averaged serum Ca × P only (ß = -0.378, p = 0.001; ß = -0.263, p = 0.018, respectively). However, in PF4-H Ab-positive patients, the extent of ΔABI did not correlate with PF4-H Ab titers (r = -0.021, p = 0.921). CONCLUSIONS: PF4-H Ab positivity, along with high levels of serum Ca × P, played a potential role in the progression of PAD over time.

Moscatilin induces apoptosis and mitotic catastrophe in human esophageal cancer cells.

Moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii, has been shown to possess anticancer activity. We examined the effect of moscatilin on human esophageal cancer cells, including squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cells and its possible mechanisms. Moscatilin suppressed the growth of both the histological cell lines in a dose- and time-dependent manner. Morphological changes indicative of apoptosis and mitotic catastrophe were observed following moscatilin treatment. The population of cells in the sub-G1 phase and polyploidy phase significantly increased after treatment. Immunofluorescence revealed multipolar mitosis and subsequent multinucleation in moscatilin-treated cells, indicating the development of mitotic catastrophe. Western blot showed a marked increase in expressions of polo-like kinase 1 and cyclin B1 after exposure to moscatilin. In conclusion, moscatilin inhibits growth and induces apoptosis and mitotic catastrophe in human esophageal SCC- and ADC-derived cell lines, indicating that moscatilin has broad potential against esophageal cancer.

Cyclin D1 expression in podocytes: regulated by mitogens in collaboration with integrin-extracellular matrix interaction through extracellular signal-regulated kinase.

Cyclin D1 plays significant roles in cell cycle entry and migration. We have documented that both integrin α3ß1 expressions and the number of podocytes were reduced in focal segmental glomerulosclerosis. We wondered whether integrin-extracellular matrix (ECM) interaction was involved in the regulation of cyclin D1 expression, and the possible signaling pathways in mitogen-stimulating podocytes. Cultured podocytes were divided into serum (mitogens/growth factors)-starved and serum-stimulated groups. Reverse transcription polymerase chain reaction was used to detect cyclin D1 mRNA, and Western blot analysis was used to measure protein concentrations of cyclin D1 and extracellular signal-regulated kinase (ERK) activation (p-ERK/ERK). The integrin-ECM interaction was blocked by anti-ß1-integrin monoclonal antibody or RGDS (Arg-Gly-Asp-Ser). The MEK inhibitor, U0126, was used to inhibit ERK activation. The results showed that there was little cyclin D1 protein in serum-starved groups, but it was abundant in serum-stimulated groups. Both cyclin D1 mRNA and protein levels were reduced in serum-stimulated podocytes after blocking integrin-ECM interaction. ERK activation in serum-stimulated podocytes was significantly decreased after blocking integrin-ECM interaction. Cyclin D1 mRNA and protein concentrations in serum-stimulated podocytes were reduced after blocking ERK activation by U0126. We demonstrate that integrin-ECM interaction collaborates with mitogens to activate ERK/mitogen-activated protein kinase pathways which are essential for cyclin D1 expression in podocytes.

Image-guided intensity modulated radiotherapy with helical tomotherapy for postoperative treatment of high-risk oral cavity cancer.

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.

Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment--case report.

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.

Concurrent chemoradiotherapy with helical tomotherapy for oropharyngeal cancer: a preliminary result.

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.

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomotherapy.

BACKGROUND: To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer. METHODS: Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m2 intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). RESULTS: The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully. CONCLUSION: HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted.