Therapeutic Oncology Research Articles

Choosing Wisely: Opportunities for improving value of cancer care in the Deep South.

13 Background: Under the Choosing Wisely (CW) Campaign, the American Society of Clinical Oncology (ASCO) and the American Society of Therapeutic Radiology and Oncology (ASTRO) recommend against non-evidence-based costly medications, tests, and procedures. CW recommendation adherence in the Deep South is largely unknown, and opportunities to reduce overuse and costs may exist. Methods: Analysis of administrative claims and tumor registry data from 12 cancer centers of the University of Alabama Health System Cancer Community Network, for Medicare beneficiaries ≥65 years old with cancer. Main outcome: percent of beneficiaries adhering to 9 CW recommendations. Results: 2012-2015 (Q1) adherence varied across CW recommendations and cancer centers, and increased over time for CW 2 and 7, decreased for 3, 5, and 6, and did not change for others. Conclusions: Opportunities to improve quality and value of cancer care exist in the Deep South. Research should understand how to minimize use of non-evidence based medications, tests, and procedures. [Table: see text]

Postoperative radiotherapy treatment evolution in prostate cancer patients: A trend moving away from guidelines?

111 Background: Randomized prospective clinical trials have demonstrated the benefit of adding postoperative radiotherapy (P-RT) for patients with prostate cancer with adverse pathological factors who underwent radical prostatectomy. Based on scientific evidence, the American Urological Association and American Society of Therapeutic Radiologists and Oncology, recommend offering P-RT to this type of patients. Methods: Retrospective analysis of 156,795 patients with prostate cancer diagnosed between 2004 and 2012, who underwent radical prostatectomy. The clinic-pathological information has been extracted from the database "Surveillance Epidemiology and End Results Program". Stage IV patients, and those with "Unknown" information on the type of surgery, radiotherapy, stage or grade, were excluded. Results: Stage II was the most common (81.9%), followed by stage III (18% of the patients). A 60% of the patients had Gleason > / = 8. Only 11.7% of the patients were > / = 70 years old. Treatment with P-RT decreased significantly between 2004 and 2012 (-0.44%; p = 0.0003). Analyzed by subgroups, P-RT decreased significantly in stage II (-0.72%; p < 0.0001) and III (-2.69%; p = 0.005), in patients with Gleason 6-7 (-1.05%; p = 0.0002) and > / = 8 (-1.79%; p = 0.0001) and < 70 years (-0.37%; p = 0.0001), whereas in > / = 70 years decreased but not significantly (-0.53%; p = 0.13). Conclusions: The use of P-RT in patients with prostate cancer who underwent radical prostatectomy is declining. What is most striking, is that the magnitude of this decline, is greatest in patients with higher risk factors, as the percentage of patients with Gleason score > / = 8 and/or Stage III (extracapsular invasion and/or involvement of seminal vesicles) receiving P-RT, declined more than the decline in the percentage of patients with Gleason 6-7 and/or stage II receiving P-RT, which clearly departs from the recommendations contained in the main treatment guidelines.

Impact of Premium Rewards for the Promotion of Innovative Drug Discovery on the Japanese Pharmaceutical Market: An Analysis by Therapeutic Area.

A new incentive program, "Premium Rewards for the Promotion of Innovative Drug Discovery and Resolution of Off-Label Use, etc," was introduced in Japan in 2010 and subsequently applied in 2010, 2012, and 2014. In our previous study, we reported statistical evidence regarding the attributes of drugs for which these premium rewards were used. We found that orphan drugs and drugs in certain therapeutic areas, including neuroscience, oncology, and immunology, were likely to receive rewards. However, that investigation was not conducted to clarify how the rewards system affects pharmaceutical sales or whether drugs that received rewards led to more profits for pharmaceutical companies. The data set for this study was a list of the 500 top-selling pharmaceuticals in Japan from 2010 to 2014, which was obtained from the IMS Japan Pharmaceutical Market database. To clarify the effect of the rewards system on different therapeutic areas, total sales and quantity sold were compared between drugs that received rewards and those that did not. The rewards system positively affected drug sales in specific therapeutic areas, including those with Anatomical Therapeutic Chemical (ATC) classifications neuroscience (N) and oncology (L), as well as the quantity sold of neuroscience-related drugs. Our study suggests that this system has been working according to its original aim of promoting the development of innovative drugs in Japan.

第52回群馬放射線腫瘍研究会抄録集

第52回群馬放射線腫瘍研究会抄録集

第53回群馬放射線腫瘍研究会抄録集

第53回群馬放射線腫瘍研究会抄録集

NPred: QSAR classification model for identifying plant based naturally occurring anti-cancerous inhibitors

Prediction of naturally occurring plant based compounds as anticancer agents is the key to developing new chemical entities in the area of therapeutic oncology. A webserver for assessing anticancer potential of phytomolecules has been developed.

A quantitative analysis of therapeutic cancer vaccines in phase 2 or phase 3 trial.

Despite the progress that has been made in other forms of cancer therapy, Provenge® (Sipuleucel-T) is the only FDA-approved vaccine for the treatment of cancer. To understand the current landscape of therapeutic oncology vaccines we performed a quantitative analysis of phase 2 and phase 3 therapeutic cancer vaccine trials. We highlight shifts in trends for the vaccine platforms examined, common adjuvant use, target indications, antibody or treatment combinations between past and recent trials as well as discuss the relationship between these trends and ratio between the number of phase 3: phase 2 for different vaccine platforms. Despite the poor success rate in vaccine approvals, registration of phase 3 trials between 2010 and 2014 were stable indicating continued investment and efforts towards development of immunotherapeutic vaccines.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-015-0093-x) contains supplementary material, which is available to authorized users.

Evaluation of knowledge, attitude, and practice regarding positron emission tomography scan: A cross-sectional survey

Background and Objectives: Positron emission tomography (PET) scan is a radionuclide imaging technique with implications in diagnostic and therapeutic oncology. Due to the complexity in the technique and cost factor, this technique has not been popular among the general and specialty dental practitioners. This survey study utilizes the Likert item to evaluate the intensity of response toward the technical and practical aspects of PET scan in dentistry. Materials and Methods: A representative population of 500 respondents was chosen by randomization. These respondents were either postgraduates or staff of various dental specialties. A close-ended questionnaire was provided inclusive of the Likert items. Simple arithmetic percentages were calculated to evaluate the knowledge and practice. One-way ANOVA test was done to evaluate the Likert items and regression analysis was done to find a correlation between the questions asked in attitude. Result: Statistically significant values ( P = 0.0010) were obtained while evaluating the Likert items. Linear regression analysis showed a strong correlation between the questions asked in attitude. Conclusion: The overall impression of the survey revealed that the knowledge of the respondents was above optimum. However, the responses in attitude revealed a lack of practical knowledge and inhibitions pertaining to prescribe PET scan in dentistry.

第49回群馬放射線腫瘍研究会抄録

第49回群馬放射線腫瘍研究会抄録

第51回群馬放射線腫瘍研究会抄録

第51回群馬放射線腫瘍研究会抄録

第48回群馬放射線腫瘍研究会抄録

第48回群馬放射線腫瘍研究会抄録

MP74-09 P2PSA AND DERIVATIVES (%P2PSA AND PHI) ACCURATELY PREDICT PROSTATE CANCER IN OBESE MEN FROM A MULTICENTER PROSPECTIVE EUROPEAN STUDY

be a more robust determinant of patient outcome compared with the American Society for Therapeutic Radiology and Oncology (ASTRO) definition (three consecutive increases of PSA). However, the Phoenix definition is not suitable for comparing BF of BT and that of radical prostatectomy (RP) because BF after RP is diagnosed when PSA >0.2ng/mL and a large portion of the patients undergo salvage therapy before PSA reaches 2.0 ng/mL. The objective of this study is to compare a new definition of BF, PSA>0.2ng/mL with three consecutive increases (NTMC definition), with the Phoenix definition and the ASTRO definition. METHODS: A total of 1442 patients with clinically localized PCa were treated with BT between September 2003 and October 2010 at our institution, and followed at least 36 months (22 to 118, median 70.0 months). The patients were treated with seed implantation using I-125 with or without EBRT combination. The patients may have neoadjuvant androgen deprivation therapy (ADT), but ADT after BT was not performed in any of the cases before the diagnosis of disease recurrence. Sesitivity and specificity of each definition are calculated and compared. True failure is confirmed by clinical failure. Possible failure (PF) is defined as rising PSA toward the end of observation without clear evidence of clinical recurrence. There were 46 PF cases and they were excluded from the study. RESULTS: Sensitivity and specificity of the Phoenix, the ASTRO, and our definition are shown in a table. NTMC definition showed much higher sensitivity and slightly lower specificity compared to the Phoenix definition. NTMC definition had similar sensitivity and higher specificity to the ASTRO definition. Neoadjuvant ADT lowered sensitivity of the Phoenix definition, and raised specificity of the Phoenix and our definition. CONCLUSIONS: NTMC definition of BF after BT such as PSA>0.2ng/mL with three consecutive increases showed sufficiently high sensitivity and specificity. The definition is useful especially the cases with neoadjuvant ADT, or when comparing therapeutic effect of BT and RP.

Long-term results of radiation oncology seminar for medical students and residents held between 1995 and 2011: career paths of the participants

The radiation oncology seminar for medical students and residents was initiated by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) with the aim of increasing the numbers of radiation oncologists. We investigated the long-term results related to the career paths of the program participants. This study enrolled 531 individuals who were medical students and residents at the time of program participation, between 1995 and 2011. We surveyed participants with regard to their affiliation status with the Japan Radiological Society (JRS) and JASTRO and whether they were board-certified radiation oncologists. Forty-two percent of the participants were members of JRS and 26.4 % were members of JASTRO. The membership status with JASTRO was investigated in program participants from 2004 to 2009, and comparison by status revealed that 30.1 % of medical students and 47.2 % of residents were members, with a significant difference (p = 0.013). As high as 92.3 % of the participants in the 1995-2001 cohort who had joined JRS and JASTRO were board-certified radiation oncologists. This program has greatly contributed to increasing the numbers of radiation oncologists. Because residents had a higher rate of affiliation than medical students, it is necessary to share information with not only medical universities, but also teaching hospitals.

Direct one-step labeling of cysteine residues on peptides with [11C]methyl triflate for the synthesis of PET radiopharmaceuticals

Radiolabeled peptides have emerged as an attractive platform for the diagnostic and therapeutic oncology. However, the (11)C-radiolabeling of peptides for positron emission tomography (PET) has been poorly explored, owing to the relatively short half-life of carbon-11 (t 1/2 = 20.3 min) and time-consuming multi-step radiochemical reactions. Existing methods have found limited use and are not routinely encountered in the production of radiotracers. Herein, we propose a facile one-step direct (11)C-methylation of cysteine residues in peptides using [(11)C]methyl triflate under ambient temperatures (20 °C) and short reaction times, on the order of seconds. Good regioselectivity of this method was demonstrated by HPLC in a simple peptide (glutathione, GSH) and a more complex test decapeptide (Trp-Tyr-Trp-Ser-Arg-Cys-Lys-Trp-Thr-Gly) bearing multiple nucleophilic sites. In addition, we extend this method towards the synthesis of [(11)C]Cys(Me)-[Tyr(3)-octreotate] as a demonstration of applicability for peptides of biological interest. This octreotate derivative was obtained in non-decay-corrected radiochemical yields of 11 ± 2 % (n = 3) with a synthesis time of approx. 30 min.

Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo

Poor oral bioavailability of chelidonine, a bio-active ingredient of Chelidonium majus, showing anti-cancer potentials against cancer cells with multidrug resistance, makes its optimal use rather limited. To address this problem, we encapsulated chelidonine in biodegradable poly(lactide-co-glycolide) (PLGA) polymers and evaluated nano-chelidonine's (NCs) anti-cancer efficacy vis-à-vis free chelidonine (FC) against HepG2 cells and also evaluated its bioavailability in mice. Physicochemical characteristics indicated that stable spherical NC were formed in nanometer size range (123±1.15nm) with good yield (86.34±1.91%), better encapsulation efficiency (82.6±0.574%), negative surface charge (−19.6±2.48mV) and ability of prolonged and sustained release of chelidonine. Fourier transform infrared analysis revealed that NC resembled similar peaks as that of FC suggesting effective encapsulation in PLGA. NC exhibited rapid cellular uptake and stronger apoptotic effect (∼46.6% reduced IC50 value) than FC, blocking HepG2 cells at G2/M phase. p53, cyclin-D1, Bax, Bcl-2, cytochrome c, Apaf-1, caspase-9 and caspase-3 expressions also corroborated well to suggest greater anticancer potentials of NC. Our in vivo studies demonstrated NC to be more bio-available than FC and showed a better tissue distribution profile without inducing any toxicity (100mg/kg bw) in mice. Unlike FC, NC could permeate into brain tissue, indicating thereby NC's better potentials for use in therapeutic oncology.

PET imaging using radiolabelled antibodies: future direction in tumor diagnosis and correlate applications

Immuno-positron emission tomography (PET) is a new imaging tool that finds application in diagnostic as well as in prognostic and therapeutic oncology. Monoclonal antibodies (mAbs) present the unique ability to selectively bind specific antigens produced by tumors, establishing the presence, location, and number of neoplastic foci. They are produced in unlimited quantities with absolute specificity using the hybridoma method. Treatment with mAbs can have different forms: they can be administered alone or can be combined with a radioactive molecule, which then delivers the radiation directly to the tumor cells. In immuno-PET, mAbs are labeled with various radionuclides and used in cancer patients who produce tumor-associated antigens. In this review we will discuss immuno-PET applications in tumor diseases, focusing on the technique, mAbs, positron emitter selection, and on its future applications.

SU-E-T-456: Prospective Investigation of Feasibility of Three-Dimensional Treatment Planning of Intracavitary Brachytherapy for Cervical Cancer Based On Computed Tomography Images

Purpose: Our aim of this study was to prospectively investigate the feasibility of three‐dimensional (3D) treatment planning of intracavitary brachytherapy for cervical cancer based on computed tomography (CT) images. Two‐dimensional (2D) treatment planning based on Manchester method and the 3D treatment planning based on Groupe Europeen de Curietherapie‐European Society for Therapeutic Radiology and Oncology recommendations were compared using 2D and 3D‐based dose evaluation indices. Methods: The 2D and 3D treatment plans were made on Oncentra for six patients with stage IB‐IIB cervical cancer, who had undergone intracavitary brachytherapy (five fractions at 6Gy/fraction). Planning CT images were acquired on a 20‐slice CT scanner at the lithotomy position after inserting the applicator. Point A‐based and D90 dose prescriptions were employed for 2D and 3D treatment planning, respectively. The GTV plus 1‐cm margin was defined as a CTV in 3D treatment planning. The two kinds of treatment plans were evaluated by a conformity index (CI), homogeneity index (HI), and tumor control probability (TCP) for CTV, and doses at bladder and rectum evaluation points, D2cc, and normal tissue complication probability (NTCP) for organs at risk (OAR). Results: The CIs for 2D and 3D plans were 2.59 ± 0.59 and 1.12 ± 0.18 (p < 0.05), respectively, and the HIs were 2.18 ± 0.28 (2D) and 1.34 ± 0.27 (3D) (p < 0.05). The bladder D2cc for 2D and 3D plans were 378 ± 58.2 cGy and 504 ±47.2 cGy (p < 0.05), respectively, and the rectum D2cc were 316 ± 58.3 cGy (2D) and 455 ± 36.1 cGy (3D) (p < 0.05). There were no statistical significant differences for the TCP and NTCP. Conclusion: The 3D treatment planning could provide better dose conformity and uniformity in CTVs. The results suggested that the doses for OAR with 2D treatment planning may be underestimated.

CPC-146 Treatment of Glioblastoma Recurrences: Role of Chemotherapy – Retrospective and Descriptive Study Within 3 Centres of the N.E.N.O. Group (NorthEast Neuro-Oncology)

BackgroundGlioblastoma multiforme (GBM) are primary brain tumours that are currently incurable. Despite a well codified first-line treatment with concomitant radio-chemotherapy (temozolomide), recurrences of GBM occur and have limited treatment options....

A phase II study of hypofractionated proton therapy for prostate cancer

Background. Hypofractionated radiotherapy potentially offers therapeutic gain for prostate cancer. We investigated the feasibility of hypofractionated proton therapy (PT). Material and methods. Eighty-two patients with biopsy-proven T1-3N0M0 prostate adenocarcinoma and no history of androgen deprivation therapy were randomly assigned to five different dose schedules: Arm 1, 60 CGE (cobalt gray equivalent = proton dose in Gy × 1.1)/20 fractions/5 weeks; Arm 2, 54 CGE/15 fractions/5 weeks; Arm 3, 47 CGE/10 fractions/5 weeks; Arm 4, 35 CGE/5 fractions/2.5 weeks; or Arm 5, 35 CGE/5 fractions/5 weeks. Results. The median follow-up duration was 42 months (11–52 months). The acute GI and GU grade ≥ 2 toxicity rates were 0 and 5%, respectively. The late GI and GU grade ≥ 2 toxicity rates were 16% and 7%, respectively. The best arm for acute GU toxicity was Arm 3, while that for late GI toxicity was Arm 2 in which none had grade ≥ 2 toxicity. The four-year American Society for Therapeutic Radiology and Oncology and Nadir + 2ng/ml BCF free survival (BCFFS) rates were 85% and 86%, respectively. Conclusions. Hypofractionated PT for patients with prostate adenocarcinoma as used in this study is feasible with an acceptable toxicity profile. As the BCFFS rates do not seem to be inferior to those produced using conventional fractionation, the application of hypofractionated PT may save patients time and money.

&lt;I&gt;In Vitro&lt;/I&gt; Investigation on the Magnetic Thermochemotherapy Mediated by Magnetic Nanoparticles Combined with Methotrexate for Breast Cancer Treatment

Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. In therapeutic oncology, hyperthermic adjuvant chemotherapy termed as thermochemotherapy plays an increasing role in multimodality cancer treatment. Currently, targeted nanothermotherapy is one of the effective hyperthermia approach based on magnetic nanoparticles (MNPs), which can be achieved by applying biocompatible nanoscaled metallic particles that convert electromagnetic energy into heat, for instance, magnetic fluid hyperthermia (MFH) mediated by superparamagnetic iron oxide nanoparticles (SPIONs). Upon exposure under alternative magnetic field (AMF), SPIONs can generate heat through oscillation of their magnetic moment. Nowadays, clinical trials at phase II are now under investigations for MFH on patients in Germany and Japan and demonstrate very inspiring for cancer therapy. In this work we explore the feasibility and effectiveness of magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate, an anti-cancer drug, for breast cancer comprehensive treatment. Amino silane coated MNPs as agent of MFH were prepared by the chemical precipitation method. Physiochemical characterizations on MNPs have been systematically carried out by various instrumental analyses. Inductive heating property of the MNPs was evaluated by monitoring the temperature increase of the MNPs suspension under AMF. The in-vitro cytotoxicity results on human breast cancer cell MCF-7 by CCK-8 assay indicated the bi-modal cancer treatment approach for combined MFH and chemotherapy is more effective than mono-modal treatment, indicating a thermal enhancement effect of hyperthermia on drug cytocoxicity. The magnetic thermochemotherapy mediated by MNPs combined with methotrexate can realize cancer comprehensive treatment thus has great potential in clinical application.