Improving outcomes in high-risk prostate cancer with radiotherapy

There have been significant improvements in the radiotherapeutic management of patients with high risk prostate cancer. Randomized trials have clearly demonstrated improved outcomes with the combination of radiotherapy in conjunction with androgen deprivation. While these trials have utilized low doses of radiotherapy in the range of 70 Gy, recent studies have suggested that significant benefits of combined androgen deprivation therapy with dose escalated radiotherapy are also observed. The use of high radiation dose levels in the setting of high risk prostate cancer is important, and strategies which combine external beam radiotherapy with a brachytherapy boost may provide an opportunity for even greater intensification of the radiation dose to the prostate target. Systemic therapies, second generation anti-androgen therapy and novel targeted agents integrated with radiotherapy will open up new vistas and challenges for further improved outcomes in patients with high-risk disease.     

Posterior kV-CBCT scanning of the head and neck region minimizes doses to critical organs with sustained image quality

We evaluated the absorbed dose to critical organs, as well as the image quality, at different partial angles in kV-CBCT (Cone Beam Computed Tomography) scanning of the head and neck region. CBCT images of phantom from a 200° rotation were performed by using three different scanning paths, anterior, posterior, and right lateral with Catphan504 and RANDO phantoms. Critical organ dose was measured using TLD 100H in the RANDO phantom. The image quality of those phantoms was evaluated, using HU uniformity, HU linearity, contrast-to-noise ratio, low contrast visibility and spatial resolution with the Catphan504 dataset; and 5-point grading scales for the RANDO phantom dataset by five radiation oncologists. The image qualities from Catphan504 and RANDO phantom of every scanning path were comparable, with no statistically significant difference (p ≥ 0.05). However, there was a significant difference in the critical organ dose in all paths (p < 0.05), depending on the critical organ location and the scanning direction. Scanning directions show no effects on the image quality. Differences in absorbed dose to critical organs should were evaluated. The posterior scanning path for the CBCT was deemed preferable due because of considerably lower doses to several critical organs of the head and neck region.     

Transrectal implantation and stability of gold markers in prostate bed for salvage radiotherapy of macroscopic recurrences

Background and purposeThe objective of the study was to verify the stability of gold markers in the prostatic bed (PB) during salvage radiotherapy.Material and methodsSeven patients, diagnosed with a macroscopic nodule visible on MRI, underwent targeted MRI-guided biopsies. Three gold markers were implanted into the PB close to the relapsing nodule for CT/MRI fusion. A dose of 60 Gy was delivered using IMRT to the PB followed by a dose escalation up to 72 Gy to the macroscopic nodule. Daily anterior and left-lateral kV-images were acquired for repositioning. The coordinates of the center of each marker were measured on the two kV-images. The distance variations (Dvar) of the markers in the first session and the subsequent ones were compared.ResultsNo marker was lost during treatment. The average distance between markers was 7.8 mm. The average Dvar was 0.8 mm, in absolute value. A total of 380/528 (72%) Dvar were ⩽1 mm. A Dvar greater than 2 mm was observed in 5.7% of measurements, with a maximum value of 4.8 mm.ConclusionsDespite the absence of the prostate, the implantation of gold markers in the PB remains feasible, with Dvar often less than 2 mm, and could be used to develop new approaches of salvage focal radiotherapy on the macroscopic relapse after prostatectomy.     

Use of planar kV vs. CBCT in evaluation of setup errors in oesophagus carcinoma radiotherapy

Aim

The aim of this study is to evaluate differences in terms of the setup errors observed using kV planar image compared to CBCT for oesophageal cancer patients.

Background

Planar kV images are quick to acquire but only allow the observation of bony structures. CBCT allows the evaluation of soft tissues, which includes the oesophagus (and tumour) and OAR, giving a more accurate verification of the positioning.

Materials and Methods

All patients were imaged with both techniques between January 2012 and March 2014 were included in the study (16 patients, 212 kV images and 116 CBCT images). Differences between the setup errors observed on the two images modalities were studied. A correlation study between TNM staging, tumour location and immobilization systems with setup errors was also done. Finally, the calculation of systematic and random errors allowed to determine the CTV–PTV margin.

Results

A significant discrepancy (p < 0.05) between the setup errors observed with kV and CBCT was observed in the lateral direction. No statistical correlation was found between setup errors and tumour location, immobilization system or TNM staging. The CTV–PTV margin was smaller with CBCT in the vertical (0.6 cm vs. 0.9 cm) and longitudinal (0.7 cm vs. 1 cm) directions and smaller with kV for the lateral directions (0.8 cm vs. 0.9 cm).

Conclusions

The chosen modality influences the setup error observed which will influence the correction applied. Allowing a better observation of the volumes of interest, CBCT should be the modality of choice in this pathology. The CTV–PTV margins could be shrunk if CBCT is used.     

Stereotactic radiotherapy for early lung cancer: Evidence-based approach and future directions

AimTo review key studies evaluating stereotactic radiotherapy in the setting of early-stage non-small cell lung cancer (NSCLC) for inoperable or high-risk patients, and discuss areas of ongoing research and clinical trials.BackgroundThe use of stereotactic radiotherapy for the treatment of early stage non-small cell lung cancer (NSCLC) has increased rapidly over the past decade. Numerous studies have reported outcomes for patients treated with SBRT who are unfit for surgical resection, or at high risk of surgical complications.Materials and methodsA narrative review.ResultsThe preponderance of evidence suggests that SBRT is associated with excellent local control (∼90% at 3 years) and a favorable toxicity profile. In patients with higher operative risks, such as the elderly and patients with severe COPD, SBRT may provide a less-toxic treatment than surgery with similar oncologic outcomes. Ongoing studies are evaluating the use of SBRT for locally advanced or oligometastatic NSCLC.ConclusionsA large body of evidence now exists to support the use of SBRT for early-stage NSCLC. Decisions regarding the optimal choice of treatment should be individualized, and made in the context of a multidisciplinary team.     

Preliminary analysis for integration of spot-scanning proton beam therapy and real-time imaging and gating

PurposeSpot-scanning proton beam therapy (PBT) can create good dose distribution for static targets. However, there exists larger uncertainty for tumors that move due to respiration, bowel gas or other internal circumstances within the patients. We have developed a real-time tumor-tracking radiation therapy (RTRT) system that uses an X-ray linear accelerator gated to the motion of internal fiducial markers introduced in the late 1990s. Relying on more than 10 years of clinical experience and big log data, we established a real-time image gated proton beam therapy system dedicated to spot scanning.Materials and methodsUsing log data and clinical outcomes derived from the clinical usage of the RTRT system since 1999, we have established a library to be used for in-house simulation for tumor targeting and evaluation. Factors considered to be the dominant causes of the interplay effects related to the spot scanning dedicated proton therapy system are listed and discussed.Results/conclusionsTotal facility design, synchrotron operation cycle, and gating windows were listed as the important factors causing the interplay effects contributing to the irradiation time and motion-induced dose error. Fiducial markers that we have developed and used for the RTRT in X-ray therapy were suggested to have the capacity to improve dose distribution. Accumulated internal motion data in the RTRT system enable us to improve the operation and function of a Spot-scanning proton beam therapy (SSPT) system. A real-time-image gated SSPT system can increase accuracy for treating moving tumors. The system will start clinical service in early 2014.     

Displacements of fiducial markers in patients with prostate cancer treated with image guided radiotherapy: A single-institution descriptive study

Aim

To describe daily displacements when using fiducial markers as surrogates for the target volume in patients with prostate cancer treated with IGRT.

Background

The higher grade of conformity achieved with the use of modern radiation technologies in prostate cancer can increase the risk of geographical miss; therefore, an associated protocol of IGRT is recommended.

Materials and methods

A single-institution, retrospective, consecutive study was designed. 128 prostate cancer patients treated with daily on-line IGRT based on 2D kV orthogonal images were included. Daily displacement of the fiducial markers was considered as the difference between the position of the patient when using skin tattoos and the position after being relocated using fiducial markers. Measures of central tendency and dispersion were used to describe fiducial displacements.

Results

The implant itself took a mean time of 15 min. We did not detect any complications derived from the implant. 4296 sets of orthogonal images were identified, 128 sets of images corresponding to treatment initiation were excluded; 91 (2.1%) sets of images were excluded from the analysis after having identified that these images contained extreme outlier values. If IGRT had not been performed 25%, 10% or 5% of the treatments would have had displacements superior to 4, 7 or 9 mm respectively in any axis.

Conclusions

Image guidance is required when using highly conformal techniques; otherwise, at least 10% of daily treatments could have significant displacements. IGRT based on fiducial markers, with 2D kV orthogonal images is a convenient and fast method for performing image guidance.     

Application of leftover sample material from waterborne protozoa monitoring for the molecular detection of Bacteroidales and fecal source tracking markers

In this study, we examined the potential for detecting fecal bacteria and microbial source tracking markers in samples discarded during the concentration of Cryptosporidium and Giardia using USEPA Method 1623. Recovery rates for different fecal bacteria were determined in sewage spiked samples and environmental waters using different group-specific and host-specific PCR assays. Bacteroidales DNA recovery ranged from 59 to 71% for aliquots of supernatant collected after the elution step. The recovery of human-specific Bacteroidales DNA from sewage spiked samples was 54% in the elution step. An additional 1-7% Bacteroidales DNA was recovered after the immunomagnetic separation step, while recovery from the pellet left after the immunomagnetic separation of protozoa parasites was substantially lower. Comparison of Bacteroidales 16S rRNA gene sequences from elution and immunomagnetic separation discarded samples indicated that the distribution of clones was not statistically different, suggesting that there were no recovery biases introduced by these steps. Human- and cow-specific Bacteroidales and fecal indicator bacteria (i.e., enterococci,) were also detected in the discarded fractions of environmental samples collected from different geographic locations. Overall, the results of this study demonstrated the potential application of leftover sample fractions that are currently discarded for the PCR detection of fecal bacterial indicators and molecular source tracking.     

Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer

Aim

This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.

Estimation of tumor and local tissue dose in gold nanoparticles radiotherapy for prostate cancer

AimThe objective of this research was to estimate the dose distribution delivered by radioactive gold nanoparticles (¹⁹⁸AuNPs or ¹⁹⁹AuNPs) to the tumor inside the human prostate as well as to normal tissues surrounding the tumor using the Monte-Carlo N-Particle code (MCNP-6.1.1 code).BackgroundRadioactive gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated to treat prostate cancer in animals. In order to use them as a new therapeutic modality to treat human prostate cancer, accurate radiation dosimetry simulations are required to estimate the energy deposition in the tumor and surrounding tissue and to establish the course of therapy for the patient.Materials and methodsA simple geometrical model of a human prostate was used, and the dose deposited by ¹⁹⁸AuNPs or ¹⁹⁹AuNPs to the tumor within the prostate as well as to the healthy tissue surrounding the prostate was calculated using the MCNP code. Water and A-150 TEP phantoms were used to simulate the soft and tumor tissues.ResultsThe results showed that the dose due to ¹⁹⁸AuNPs or ¹⁹⁹AuNPs, which are distributed homogenously in the tumor, had a maximal value in the tumor region and then rapidly decreased toward the prostate–tumor interface and surrounding organs. However, the dose deposited by ¹⁹⁸Au is significantly higher than the dose deposited by ¹⁹⁹Au in the tumor region as well as normal tissues.ConclusionsAccording to the MCNP results, ¹⁹⁸AuNPs are a promising modality to treat prostate cancer and other cancers and ¹⁹⁹AuNPs could be used for imaging purposes.     

Comparison of dose distribution in IMRT and RapidArc technique in prostate radiotherapy

AimThe aim was to provide a dosimetric comparison between IMRT and RapidArc treatment plans with RPI index with simultaneous comparison of the treatment delivery time.BackgroundIMRT and RapidArc provide highly conformal dose distribution with good sparing of normal tissues. However, a complex spatial dosimetry of IMRT and RapidArc plans hampers the evaluation and comparison between plans calculated for the two modalities. RPI was used in this paper for treatment plan comparisons. The duration of the therapeutic session in RapidArc is reported to be shorter in comparison to therapeutic time of the other dynamic techniques. For this reasons, total treatment delivery time in both techniques was compared and discussed.Materials and methods15 patients with prostate carcinoma were randomly selected for the analysis. Two competitive treatment plans using respectively the IMRT and RapidArc techniques were computed for each patient in Eclipse planning system v. 8.6.15. RPIwin^® application was used for RPI calculations for each treatment plan.Additionally, total treatment time was compared between IMRT and RapidArc plans. Total treatment time was a sum of monitor units (MU) for each treated field.ResultsThe mean values of the RPI indices were insignificantly higher for IMRT plans in comparison to rotational therapy. Comparison of the mean numbers of monitor units confirmed that the use of rotational technique instead of conventional static field IMRT can significantly reduce the treatment time.ConclusionAnalysis presented in this paper, demonstrated that RapidArc can compete with the IMRT technique in the field of treatment plan dosimetry reducing the time required for dose delivery.     

Quantitative analyses of amount and localization of radiosensitizer gold nanoparticles interacting with cancer cells to optimize radiation therapy

Previous studies showed that gold nanoparticles (AuNPs) are useful radiosensitizers which optimize radiation therapy under low-dose radiation. However, the mechanisms of AuNP radiosensitization, including the amount and localization of the AuNPs interacting with cancer cells, has not yet been quantified. To answer these questions, we prepared AuNPs conjugated with anti-human epidermal growth factor receptor type 2 (HER2) antibody via polyethylene glycol (PEG) chains (AuNP-PEG-HER2ab). AuNP-PEG-HER2ab specifically bound to the HER2-expressing cancer cells and entered the cells via endocytosis. Whether endocytosis of AuNP-PEG-HER2ab occurred had no effect on radiosensitization efficacy by AuNP-PEG-HER2ab in vitro. The radiosensitization efficacy in vitro depended on dose of AuNP-PEG-HER2ab or dose of X-ray. Moreover, AuNP-PEG-HER2ab administrated into tumor-bearing mice was localized to both the periphery of the tumor tissue and near the nuclei in cancer cells in tumor deep tissue. The localization of AuNP-PEG-HER2ab in tumor tissues was important factors for in vivo powerful radiosensitization efficacy.     

SIMBOSPROST: Prevalence of metabolic syndrome and osteoporosis in prostate cancer patients treated with radiotherapy and androgen deprivation therapy: A multicentre,cross-sectional study

AimTo assess the prevalence of metabolic syndrome (MetS) and osteoporosis in patients with prostate cancer (PCa) treated with radical radiotherapy (RT) with or without androgen deprivation therapy (ADT).BackgroundWorldwide, the prevalence of MetS is estimated to range from 20% to 25% of the adult population. However, prevalence rates are much higher in PCa patients (pts) who undergo ADT.Materials and methodsMulticentre cross-sectional study of 270 pts in Spain with PCa. Patients were divided into 3 groups based on the duration of ADT (6, 12–18, ≥24 months) and compared to a control group without ADT. MetS was defined according to NCEP ATP III criteria. Osteoporosis was assessed by DEXA.ResultsA total of 270 pts, treated from November 2011 to October 2012, were included. Of these, 122 pts (47%) fulfilled the criteria for MetS. The median age of this group was significantly higher (71.3 vs. 69.38 years, p = 0.028). MetS prevalence was 50% in the control group. In pts who received ADT, prevalence was 44.8% after 6 months of ADT, 45.3% after 12–18 months, and 50% after ≥24 months (pns). Most pts (168/270; 62%) underwent DEXA. Of those tested, 78 (46.4%) had osteopenia and only 11 (6.5%) had osteoporosis.ConclusionsThe prevalence of MetS in pts with PCa treated with radical RT was higher (47%) than in the general population. However, there were no significant differences in the duration of ADT administration. The prevalence of osteoporosis was low. These findings suggest that the prevalence of MetS in PCa patients may be higher than previously reported.     

Fidelity of bacterial source tracking: Escherichia coli vs Enterococcus spp and minimizing assignment of isolates from nonlibrary sources

AIMS: The goal of the study was to improve the fidelity of library-dependent bacterial source tracking efforts in determining sources of faecal pollution. The first objective was to compare the fidelity of source assignments using Escherichia coli vs Enterococcus spp. The second objective was to determine the efficacy of using thresholds during source assignments to reduce the rate of misassignments when nonlibrary isolates (i.e. isolates from animals not used in building the identification library) are present. METHODS AND RESULTS: E. coli and Enterococcus isolates from 784 human, cow, deer, dog, chicken, and gull faecal samples were fingerprinted using BOX-PCR. Jack-knife analysis of the fingerprints showed that the overall rate of correct assignment (ORCA) of 867 E. coli isolates was 67% compared with 82% for 1020 Enterococcus isolates. In a separate blind test using similarity value and quality factor thresholds, the ORCA of 130 E. coli and 131 Enterococcus isolates were 70% and 98%, respectively. The use of these thresholds reduced misassignment of 262 nonlibrary enterococcal isolates from horses, goats, pigs, bats, squirrels, ducks, geese, and migratory song birds. Misassignment was reduced from 100% when thresholds were not used, to 47% using similarity threshold alone, and to 12% when both thresholds were used. CONCLUSIONS: The use of enterococci provides higher rates of correct source assignment compared with E. coli. The use of similarity thresholds to decide whether to accept source assignments made by computer programmes reduces the rate of misassignment of nonlibrary isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: Although both E. coli and Enterococcus spp. are still used in microbial source tracking, the use of enterococci should be preferred over the use of E. coli in DNA fingerprint-based efforts. In addition, because environmental isolates are not limited to those from animals used to build source tracking libraries, similarity thresholds should be used during source assignments to reduce the rate of misassignments.     

Assessment and evaluation of MV image guidance system performance in radiotherapy

Background and aim

The clinical use of imaging system in image guided radiotherapy (IGRT) necessitates performing periodic quality assurance of the system to be confident in applying corrections for patient set-up errors. We aim to develop and implement a quality assurance (QA) programme for megavoltage (MV) based image guidance system and assess its long term performance for a period of 3 years.

Materials and methods

Periodic QA tests were performed for the MV planar and cone beam computed tomography (CBCT) imaging system to assess the system safety, mechanical and geometrical accuracy, image quality and dose. The tests were performed using the equipment supplied by the manufacturer along with the image guidance system and using simple methods developed in-house. The test results were compared with expected or baseline values established during commissioning.

Results

The safety system was found to be functional. The results of mechanical and geometrical tests were in good agreement with the expected results. The system mechanical positioning was stable and reproducible within ±2 mm accuracy. The image quality and the imaging dose of the planar and CBCT imaging were found to agree with the baseline values and the manufacturer specifications.

Discussion

Throughout the three-year period, all the QA tests were within the specification. The mechanical and geometrical tests are most crucial as they directly affect the patient positioning accuracy.

Conclusion

We conclude that the MV image guidance system is efficient to perform IGRT and insist to perform periodic QA tests and calibration for the system.     

Isolation of phenolic constituents and characterization of antioxidant markers from sunflower (Helianthus annuus) seed extract

A new compound, benzyl alcohol β-d-apiofuranosyl-(1→6)-β-d-(4-O-caffeoyl) glucopyranoside (1), was isolated from the seed of sunflower (Helianthus annuus), together with eight known phenolic compounds: caffeic acid (2), methyl caffeoate (3), chlorogenic acid (4), 4-O-caffeoylquinic acid (5), 3-O-caffeoylquinic acid (6), methyl chlorogenate (7), 3,5-di-O-caffeoylquinic acid (8), and eriodictyol 5-O-β-d-glucoside (9). Their structures were elucidated on the basis of spectroscopic methods and chemical evidence. The antioxidative effect of the phenolic constituents from the sunflower seeds was also evaluated based on the oxygen-radical absorbance capacity (ORAC), and the fraction containing caffeic acid derivatives showed a high antioxidant potency.     

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients

The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment.