Serious gastric perforation after second stereotactic body radiotherapy for peripheral lung cancer that recurred after initial stereotactic body radiotherapy: a case report

Background

In recent reports, re-irradiation with stereotactic body radiotherapy for lung tumors in patients previously treated with thoracic radiation therapy resulted in several serious toxicities. Serious non-lung toxicities were observed mostly in patients with central tumors, but we experienced a case of fatal gastric perforation after a second stereotactic body radiotherapy in a patient with a peripheral lung tumor.

Case presentation

An 83-year-old Asian man was diagnosed with T2N0M0 lung cancer in the form of squamous cell carcinoma in the lower lobe of his left lung. He was treated with stereotactic body radiotherapy of 40 Gy in 4 fractions and the tumor decreased in size in partial response. The local tumor recurred 8 months after the first stereotactic body radiotherapy, and he was re-irradiated with a second stereotactic body radiotherapy of 50 Gy in 4 fractions. A Sengstaken–Blakemore tube was inserted below his diaphragm by laparoscopic surgery before the second stereotactic body radiotherapy in order to reduce the stomach dose by keeping his stomach apart from the tumor. Two months after the second stereotactic body radiotherapy, he developed fatal gastric perforation and gastropleural fistula penetrating his diaphragm.

Conclusions

To the best of our knowledge, this is the first report about a gastric perforation after stereotactic body radiotherapy for lung tumors and it warns of serious complication of stereotactic body radiotherapy in not only centrally located but also peripherally located tumors like in this case.

     

Interfractional diaphragm changes during breath-holding in stereotactic body radiotherapy for liver cancer

Aim and background

IGRT based on bone matching may produce a large target positioning error in terms of the reproducibility of expiration breath-holding on SBRT for liver cancer. We evaluated the intrafractional and interfractional errors using the diaphragm position at the end of expiration by utilising Abches and analysed the factor of the interfractional error.

Influence of segment width on plan quality for volumetric modulated arc based stereotactic body radiotherapy

Aim

To study the influence of segment width on plan quality for volumetric modulated arc based stereotactic body radiotherapy.

Background

The redundancy of modulation for regularly shaped small volume tumors results in creation of many small segments and an increase of monitor units, with a consequent prolongation of treatment and uncertainty in treatment delivery.

Materials and methods

Six cases each in lung, abdomen and liver were taken for the study. For each case, three VMAT SBRT plans were generated with different penalties on minimum segment width of 0.5, 1.0 and 1.5 cm. A comparison was made on the metrics of dose volume histogram, dosimetric indices, monitor units (MUs) and delivery accuracy.

Results

The mean reduction of total MUs when compared with 0.5 cm plan was observed as 12.7 ± 6.0% and 17.5 ± 7.2% for 1.0 cm and 1.5 cm of minimum segment width, respectively. The p value showed a significant degradation in dosimetric indices for 1.5 cm plans when compared with 0.5 cm and 1.0 cm plans. The average deviation of measured dose with TPS calculated was 3.0 ± 1.1%, 2.1 ± 0.84% and 1.8 ± 0.9% for 0.5, 1.0 and 1.5 cm, respectively. The calculated gamma index with pass criteria of 2% dose difference and 2 mm distance to agreement was 95.9 ± 2.8%, 96.5 ± 2.6% and 97.8 ± 1.6% as calculated for 0.5, 1.0 and 1.5 cm of penalties, respectively. In view of the trade off between delivery efficiency and plan quality, 1 cm minimum segment width plans showed an improvement.

Conclusions

VMAT SBRT plans with increased optimal value of minimum segment width showed better plan quality and delivery efficiency for stereotactic body radiotherapy.     

Cell-free DNA as a prognostic marker in stage I non-small-cell lung cancer patients undergoing stereotactic body radiotherapy

Abstract

Objective: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT).

Materials and methods: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated.

Results: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR?=?5.9, 95%CI: 1.7–19.8, p?=?0.04).

Conclusion: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients.     

Dosimetric selection for helical tomotherapy based stereotactic ablative radiotherapy for early-stage non-small cell lung cancer or lung metastases

Background

No selection criteria for helical tomotherapy (HT) based stereotactic ablative radiotherapy (SABR) to treat early stage non-small cell lung cancer (NSCLC) or solitary lung metastases has been established. In this study, we investigate the dosimetric selection criteria for HT based SABR delivering 70 Gy in 10 fractions to avoid severe toxicity in the treatment of centrally located lesions when adequate target dose coverage is desired.

Materials and Methods

78 HT-SABR plans for solitary lung lesions were created to prescribe 70 Gy in 10 fractions to the planning target volume (PTV). The PTV was set to have ≥95% PTV receiving 70 Gy in each case. The cases for which dose constraints for ≥1 OAR could not be met without compromising the target dose coverage were compared with cases for which all target and OAR dose constraints were met.

Results

There were 23 central lesions for which OAR dose constraints could not be met without compromising PTV dose coverage. Comparing to cases for which optimal HT-based SABR plans were generated, they were associated with larger tumor size (5.72±1.96 cm vs. 3.74±1.49 cm, p<0.0001), higher lung dose, increased number of immediately adjacent OARs ( 3.45±1.34 vs. 1.66±0.81, p<0.0001), and shorter distance to the closest OARs (GTV: 0.26±0.22 cm vs. 0.88±0.54 cm, p<0.0001; PTV 0.19±0.18 cm vs. 0.48±0.36 cm, p = 0.0001).

Conclusion

Delivery of 70 Gy in 10 fractions with HT to meet all the given OAR and PTV dose constraints are most likely when the following parameters are met: lung lesions ≤3.78 cm (11.98 cc), ≤2 immediately adjacent OARs which are ≥0.45 cm from the gross lesion and ≥0.21 cm from the PTV.     

Simulation studies on the effect of absorbers on dose distribution in rotational radiotherapy

The effect of cylindrical protector dimensions, material and distance from the source on the dose distribution in rotational radiotherapy was studied to assess the potential protection possibilities of small-sized radiosensitive structures, such as spinal cord. The dose distributions were evaluated in terms of dose at the protected region and surface dose, ratio of the dose at the protected region to the maximum dose, and dose gradient. High-density materials, such as lead, tungsten, gold and cerrobend, along with new polymer–metal composite ones were used in simulation studies, performed by an in-house developed Monte Carlo Radiotherapy Simulator. To ensure correct modeling of the composite materials, simulated attenuation data were verified against experimentally measured data. The dependence of the dose at the protected region from the protector diameter and the field size was established. Protectors of higher density and larger diameter provide not only lower dose at the protected region, but also steeper dose gradient and lower ratio of the dose at the protected region to the treatment dose. For the protection of small structures, high-density protectors placed further from the source allow thicker protectors to be used. The surface dose increases insignificantly for the studied protector–surface distances. The results have shown that shielding properties of composite materials are close to those of lead.     

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

AimThe aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer.Background3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use.Materials and methodsOptimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed.ResultsThe quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed.ConclusionsOptimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively.     

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.     

A set of fortran subroutines for optimizing radiotherapy plans.

Quadratic Programming techniques have been applied to the optimization of radiation field weighting in Radiotherapy planning. Wedge selection has also been included by means of an exhaustive search. The radiation dose at any point in the patient may be constrained to be less than a stated percentage of the tumour dose. The routines have been successfully interfaced into a small computer interactive planning system, but they could represent an even more powerful tool in batch and time sharing systems. Minimum operator intervention is required in their use.     

Fractionated stereotactic radiotherapy plus bevacizumab after response to bevacizumab plus irinotecan as a rescue treatment for high-grade gliomas

Aim

To evaluate the possibility of implementing a new scheme of rescue treatment after relapse or progression of high-grade glioma (HGG) treated at the first-line with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT).

Materials and methods

We retrospectively analysed data from 59 patients with relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp protocol that were treated with BVZ+CPT11 for progression between July 2007 and August 2012, after which the response was assessed according to the Revised Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of 10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three days a week. The median follow-up was 38 months.

Results

The treatment was well-tolerated by all patients. The response after nuclear magnetic resonance imaging (MRI) at 3–6 months was progression in two patients, stable disease in four, and three patients had a partial response. The median overall survival (OS) from diagnosis until death or the last control was 36.8 months. The median progression-free survival (PFS) was 10.8 months. The results from tumour sub-group analysis indicated that the PFS was not statistically significant although it seemed that it was higher in grade-III. The OS was higher in grade-III gliomas.

Conclusions

The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well-tolerated and seems to offer promising results. We believe that multi-centre prospective studies are needed to determine the long-term efficacy and toxicity of this therapeutic approach.Abbreviations: HGG, high-grade glioma; BVZ, bevacizumab; CPT11, irinotecan; FSRT, fractionated stereotactic radiotherapy; RANO, revised Assessment in Neuro-Oncology; MRI, magnetic resonance imaging; OS, overall survival; PFS, progression-free survival; TMZ, temozolomide; KPS, Karnofsky Performance Scale; VEGF, vascular endothelial growth factor; PTV, planning target volume; CAT, computed axial tomography; GTV, gross tumour volume; SEOM, Sociedad Española de Oncología Médica; ASCO, American Society of Clinical Oncology; CTCAE, common terminology criteria for adverse events; PET, positron emission tomography; CI, confidence interval; MGMT, O-6-methylguanine-DNA methyltransferase; HR, hazard ratio; CR, complete response; PR, partial response; SD, stable disease; SRS, stereotactic radiosurgery; PD, progressive disease; FLAIR, fluid-attenuated inversion recovery; NA, not applicable     

Comparison of (125)I stereotactic brachytherapy and LINAC radiosurgery modalities based on physical dose distribution and radiobiological efficacy

The goal of this study was to make a comparison between stereotactic brachytherapy implants and linear accelerator-based radiosurgery of brain tumors with respect to physical dose distributions and radiobiological efficacy. Twenty-four treatment plans made for irradiation of brain tumors with low-dose-rate (125)I brachytherapy and multiple-arc LINAC-based radiosurgery were analyzed. Using the dose-volume histograms and the linear-quadratic model, the brachytherapy doses were compared to the brachytherapy-equivalent LINAC radiosurgery doses with respect to the predicted late effects of radiation on normal brain tissue. To characterize the conformity and homogeneity of dose distributions, the conformal index, external volume index, and relative homogeneity index were calculated for each dose plan and the mean values were compared. The average tumor volume was 5.6 cm(3) (range: 0.1-19.3 cm(3)). At low doses, the calculated radiobiological late effect on normal tissue was equivalent for external-beam and brachytherapy dose delivery. For brachytherapy at doses greater than 30 Gy, the calculated equivalent dose to normal tissues was less than for external-beam radiosurgery. However, the dose-calculated homogeneity was better for the LINAC radiosurgery, with a mean relative homogeneity index of 0.62 compared to the calculated value of 0.19 for the brachytherapy (P=0.0002). These results are only predictions based on calculations concerning normal tissue tolerance. More data and research are needed to understand the clinical relevance of these findings.     

The effect of dose distribution on risk of lung cancer after inhalation of actinide oxides

The aim of this work was to estimate risk of lung tumour occurrence after inhalation of actinide oxides from published studies and rat studies in progress. For the same delivered dose, the risk increases when homogeneity of irradiation increases, i.e., the number of particles deposited after inhalation increases (small particles and (or) low specific alpha activity). The dose-effect relationships reported appear linear up to a few gray, depending on the aerosol considered, and then the slope decreases. This slope, which corresponds with the risk, can vary over one order of magnitude depending on the aerosol used. An effective threshold at about 1 Gy was not observed for the most homogeneous dose distributions. A dosimetric and biological approach is proposed to provide a more realistic risk estimate.     

Skin surface markers for stereotactic body radiation therapy of sternal metastasis

Stereotactic body radiation therapy is an effective and safe treatment modality for bone metastasis which allows clinicians to accurately target lesions to high doses while minimizing dose to organs at risk. The commercially available CyberKnife^® Xsight? Spine Tracking System (Accuray, Inc., Sunnyvale, CA) tracks static skeletal structures and eliminates the need for implanted fiducial markers (FMs). However, the Xsight? Spine Tracking system is not appropriate for bone metastases outside the spine, which are moving due to respiration and ,typically, FMs have to be implanted close to the lesion. These FMs will be used to track the dynamic target. For targets close to the surface, non-invasive fixation of the FMs to the patient's skin could be an option.     

Effects of chronic low dose rotenone treatment on human microglial cells

Background

Exposure to toxins/chemicals is considered to be a significant risk factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is the naturally occurring herbicide rotenone that is now used widely in establishing PD models. We, and others, have shown that chronic low dose rotenone treatment induces excessive accumulation of Reactive Oxygen Species (ROS), inclusion body formation and apoptosis in dopaminergic neurons of animal and human origin. Some studies have also suggested that microglia enhance the rotenone induced neurotoxicity. While the effects of rotenone on neurons are well established, there is little or no information available on the effect of rotenone on microglial cells, and especially cells of human origin. The aim of the present study was to investigate the effects of chronic low dose rotenone treatment on human microglial CHME-5 cells.

Methods

We have shown previously that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y cells and therefore used these cells as a control for inclusion body formation in this study. SH-SY5Y and CHME-5 cells were treated with 5 nM rotenone for four weeks. At the end of week 4, both cell types were analysed for the presence of inclusion bodies, superoxide dismutases and cell activation (only in CHME-5 cells) using Haematoxylin and Eosin staining, immunocytochemical and western blotting methods. Levels of active caspases and ROS (both extra and intra cellular) were measured using biochemical methods.

Conclusion

The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others. However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low dose) induced damage.

     

Using electron beam radiation to simulate the dose distribution for whole body solar particle event proton exposure

As a part of the near solar system exploration program, astronauts may receive significant total body proton radiation exposures during a solar particle event (SPE). In the Center for Acute Radiation Research (CARR), symptoms of the acute radiation sickness syndrome induced by conventional radiation are being compared to those induced by SPE-like proton radiation, to determine the relative biological effectiveness (RBE) of SPE protons. In an SPE, the astronaut’s whole body will be exposed to radiation consisting mainly of protons with energies below 50 MeV. In addition to providing for a potentially higher RBE than conventional radiation, the energy distribution for an SPE will produce a relatively inhomogeneous total body dose distribution, with a significantly higher dose delivered to the skin and subcutaneous tissues than to the internal organs. These factors make it difficult to use a ⁶⁰Co standard for RBE comparisons in our experiments. Here, the novel concept of using megavoltage electron beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation is described. In these studies, Monte Carlo simulation was used to determine the dose distribution of electron beam radiation in small mammals such as mice and ferrets as well as large mammals such as pigs. These studies will help to better define the topography of the time-dose-fractionation versus biological response landscape for astronaut exposure to an SPE.