An end-to-end postal audit test to examine the coincidence between the imaging isocenter and treatment beam isocenter of the IGRT linac system for Japan Clinical Oncology Group (JCOG) clinical trials

PurposeThe aim of this study was to develop an end-to-end postal audit test to examine the coincidence between the imaging isocenter and treatment beam isocenter of the image guided radiotherapy (IGRT) linac system for Japan Clinical Oncology Group (JCOG) trials, as a part of IGRT credentialing of institutions participating in JCOG trials.MethodsWe developed an end-to-end postal audit test to verify radiation positional errors associated with IGRT techniques. This test is intended for simulating a clinical IGRT flow and uses a static cubic phantom measuring 15 × 15 × 15 cm³ and weighing approximately 3.4 kg. The phantom has four gold fiducial markers and a spherical dummy target for setup, with known shift values from the phantom center. Two pairs of Gafchromic RTQA2 films were inserted 5 mm from the phantom’s anterior-posterior and right-left surfaces. Radiation positional errors at the isocenter were determined by analyzing the center of the radiation field on the films and the known shift values of the dummy target. The test was performed on 47 IGRT devices at 35 institutions.ResultsRadiation positional errors were within acceptance levels (1 mm/1°) for 42 IGRT devices (89.4%) in the first check. Median time to complete IGRT credentialing was 11.5 days. This audit method was applicable for any radiotherapy machine with an IGRT device.ConclusionsA postal audit test to verify radiation positional errors for JCOG trials was successfully developed. In the postal audit, all but one institution passed this credentialing item within two trials.     

Time and frequency to observe fiducial markers in MLC-modulated fields during prostate IMRT/VMAT beam delivery

ObjectiveThis work investigates the time and frequency to observe fiducial markers in MLC-modulated fields during intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) beam delivery for real-time prostate localization.MethodsThirty seven prostate patients treated with IMRT or VMAT were included in this retrospective study. DRR images were generated for all MLC segments/control points using the TPS. The MLC leaf pattern of each control point was overlaid on the DRR, and the number of fiducials within the MLC opening was analyzed. EPID images of fiducials in a pelvic phantom were obtained to demonstrate the fiducial visibility during modulated beam delivery.ResultsGold fiducials were visible on EPID images. The probability of seeing a number of fiducials within the MLC opening was analyzed. At least one fiducial was visible during 42 ± 2% and 52 ± 2% beam-on time for IMRT of the prostate with and without lymph nodes, and during 81 ± 4% and 80 ± 5% beam-on time for VMAT of the prostate with and without lymph nodes, respectively. The mean time interval to observe at least one fiducial was 8.4 ± 0.7 and 5.9 ± 0.5 s for IMRT of the prostate with and without the lymph nodes, respectively, and 1.6 ± 0.1 s for VMAT prostate patients. The estimated potential dosimetric uncertainty was 7% and 2% for IMRT and VMAT, respectively.ConclusionsOur results demonstrated that the time and frequency to observe fiducial markers in MLC-modulated fields during IMRT/VMAT beam delivery were adequate for real-time prostate localization. The beam’s eye view fiducial positions could be used for intrafractional target monitoring and motion correction in prostate radiotherapy.     

Adjuvant gamma knife surgery and image-guided,intensity-modulated radiation therapy for the treatment of sacral chordomas

AimThe aim of this study was to confirm whether patients with sacral chordoma benefit from adjuvant radiotherapy and to determine the optimal photon radiotherapy module for comprehensive treatment.BackgroundChordoma is a rare slow-growing neoplasm arisen from cellular remnants of the notochord. About 50% occur in the sacrococcygeal region. Surgical resection and adjuvant radiation therapy are recommended treatment due to the improving local control rate.Materials and methods118 patients treated by surgery and adjuvant radiotherapy from August 2003 to May 2015 were retrospectively analyzed. All patients received surgical resection after diagnosis. Among these patients, 44 were treated by exclusive surgery, and 48 were treated with adjuvant image-guided, intensity-modulated radiation therapy (IG-IMRT). In addition, 26 patients were treated with gamma knife surgery (GKS) after surgical resection. The median follow-up was 54 months for all patients. Kaplan–Meier analysis was used to calculate recurrence-free survival (RFS) overall survival (OS).ResultsPatients treated with adjuvant radiotherapy had better RFS (p = 0.014) than those treated exclusively by surgery. The patients in the IG-IMRT group exhibited better recurrence-free survival (p = 0.01) than the GKS group. Moreover, in the IG-IMRT group, patients treated by higher dose were associated with better RFS (p = 0.04). No significant difference in OS was found. No grade 3 late toxicity was found.ConclusionsWe confirmed that adjuvant radiotherapy improved RFS but not OS in sacral chordoma patients after surgery. Furthermore, favorable RFS and low adverse event rates were observed following IG-IMRT. Our results suggest that high dose IG-IMRT is an appropriate module of adjuvant radiotherapy for sacral chordoma patients.     

胸部肿瘤患者放疗中肺功能指标的变化及放射性肺炎的影响因素分析

目的:研究胸部肿瘤患者放疗中肺功能指标的变化并分析放射性肺炎的影响因素。方法:将2018年3月至2019年3月于我院接受放疗的胸部肿瘤患者100例记为观察对象,按照是否发生放射性肺炎分为肺炎组28例与无肺炎组72例。分别比较两组的临床资料、放疗前后肺功能及放疗参数,并采用多因素Logistic回归分析放射性肺炎的影响因素。结果:放疗后两组第1秒用力呼气容积(FEV_1)、FEV_1/用力肺活量(FVC)、一氧化碳弥散量(DLCO)均高于放疗前,且肺炎组放疗前、后FEV_1、FEV_1/FVC、DLCO均低于无肺炎组(均P0.05)。两组年龄、肿瘤类型、化疗史、美国东部肿瘤合作组(ECOG)评分、放疗靶区比较差异有统计学意义(均P0.05)。肺炎组计划靶区(PTV)、受到一定剂量以上照射的肺体积占全肺总体积的百分数(V_(dose))、平均肺计量(MLD)、正常组织并发症概率(NTCP)、总射野数高于无肺炎组(均P0.05)。经多因素Logistic回归分析可得:胸部肿瘤放疗患者放射性肺炎的独立危险因素有肺癌、化疗史、ECOG评分为2分、放疗靶区以肺野为主、PTV、MLD、V_(dose)、NTCP、总射野数、FEV_1、FEV_1/FVC(均P0.05)。结论:放疗可有效改善胸部肿瘤患者的肺功能,其中肺癌、化疗史、ECOG评分为2分、放疗靶区以肺野为主以及PTV、MLD、V_(dose)、NTCP、总射野数、FEV_1、FEV_1/FVC是放射性肺炎的影响因素。     

Automatic tracking of gold seed markers from CBCT image projections in lung and prostate radiotherapy

PurposeTo construct a method and software to track gold seed implants in prostate and lung patients undergoing radiotherapy using CBCT image projections.MethodsA mathematical model was developed in the MatLab (Mathworks, Natick, USA) environment which uses a combination of discreet cosine transforms and filtering to enhance several edge detection methods for identifying and tracking gold seed fiducial markers in images obtained from Varian (Varian Medical Systems, Palo Alto, USA) and Elekta (Kungstensgatan, Sweden) CBCT projections.ResultsOrgan motion was captured for 16 prostate patients and 1 lung patient.ConclusionImage enhancement and edge detection is capable of automatically tracking markers for up to 98% (Varian) and 79% (Elekta) of CBCT projections for prostate and lung markers however inclusion of excessive bony anatomy (LT and RT LAT) inhibit the ability of the model to accurate determine marker location.     

Integration of Diffusion Magnetic Resonance Tractography into tomotherapy radiation treatment planning for high-grade gliomas

IntroductionFractionated radiotherapy in brain tumors is commonly associated with several detrimental effects, largely related to the higher radiosensitivity of the white matter (WM) with respect to gray matter. However, no dose constraints are applied to preserve WM structures at present. Magnetic Resonance (MR) Tractography is the only technique that allows to visualize in vivo the course of WM eloquent tracts in the brain. In this study, the feasibility of integrating MR Tractography in tomotherapy treatment planning has been investigated, with the aim to spare eloquent WM regions from the dose delivered during treatment.MethodsNineteen high grade glioma patients treated with fractionated radiotherapy were enrolled. All the patients underwent pre-treatment MR imaging protocol including Diffusion Tensor Imaging (DTI) acquisitions for MR Tractography analysis. Bilateral tracts involved in several motor, language, cognitive functions were reconstructed and these fiber bundles were integrated into the Tomotherapy Treatment planning system. The original plans without tracts were compared with the optimized plans incorporating the fibers, to evaluate doses to WM structures in the two differently optimized plans.ResultsNo significant differences were found between plans in terms of planning target volume (PTV) coverage between the original plans and the optimized plans incorporating fiber tracts. Comparing the mean as well as the maximal dose (Dmean and Dmax), a significant dose reduction was found for most of the tracts. The dose sparing was more relevant for contralateral tracts (P < 0.0001).ConclusionThe integration of MR Tractography into radiotherapy planning is feasible and beneficial to preserve important WM structures without reducing the clinical goal of radiation treatment.     

Factors influencing the use of adaptive radiation therapy in vulvar carcinoma

AimWe aim to evaluate the variables affecting the frequency of adaptive radiotherapy (ART) in vulvar cancer.BackgroundART may be needed throughout a definitive RT course for vulvar carcinoma due to changes in patient’s anatomy and tumor response.Materials and methodsCharts of patients charts who had been treated with definitive concurrent chemo-radiotherapy for vulvar carcinoma, between January 2015 and December 2019 were inquired. Radiation therapy was delivered using intensity modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT). ART was defined as re-simulation and re-planning based on deformation in the irradiated volume by more than 1 cm. Univariate analysis was conducted to study the impact of patient’s demographics as well as tumor characteristics on the frequency of ART.Results22 patients were eligible for analysis. Median age at diagnosis was 55 years (range 43–82). Radiotherapy dose was 60−66 Gy over 30–35 fractions (fx). Median primary tumor volume was 30cc (9–140). Median Body Mass Index (BMI) was 32 (range 21–40). Thirteen out of 22 patients (59%) required ART, with median timing at 25 fx (19–31). On univariate analysis, larger primary tumor volume (> = 30cc) was associated significantly with increased frequency of ART (p value = 0.0005). There was no significant impact of ART on the frequency with respect to patient’s age, BMI, tumor stage, grade and location.ConclusionChanges in radiation target volume are common among vulvar carcinoma patients who are treated with definitive radiotherapy, especially large primary tumors. This review highlights the importance of ART for patients with vulvar carcinoma treated with definitive radiotherapy.     

Complication of radiation therapy among patients with positive S. aureus culture from genital tract

AimThe main goal of this investigation was to evaluate the influence of positive Staphylococcus aureus culture from the genital tract on patients receiving radiation therapy, suffering from carcinoma of the uterus. The other aim was to observe radiation therapy complications.BackgroundRadiation therapy of patients suffering from cervical cancer can be connected with inflammation of the genitourinary tract.Materials and methodsIn years 2006–2010 vaginal swabs from 452 patients were examined. 39 women with positive S. aureus cultures were analysed.ResultsComplications and interruptions during radiation therapy were observed in 7 (18.9%) of 37 patients with positive vaginal S. aureus culture. One of them, a 46-year-old woman developed pelvic inflammatory disease. None of the six patients who received palliative radiotherapy showed interruption in this treatment. Isolated S. aureus strains were classified into 13 sensitivity patterns, of which 8 were represented by 1 strain, two by 2 strains and three by 13, 8 and 6 strains. One strain was diagnosed as methicillin resistant S. aureus (MRSA).ConclusionsThe results of the present study show that S. aureus may generally be isolated from the genital tract of female patients with neoplastic disease of uterus but is not often observed as inflammation factor of this tract. Comparison of species’ resistance patterns may be used in epidemiological studies in order to discover the source of infections and therefore be of profound significance in the prevention of nosocomial infections.     

Impact of Pelvic Radiotherapy on Gut Microbiota of Gynecological Cancer Patients Revealed by Massive Pyrosequencing

Although pelvic irradiation is effective for the treatment of various cancer types, many patients who receive radiotherapy experience serious complications. Gut microbial dysbiosis was hypothesized to be related to the occurrence of radiation-induced complications in cancer patients. Given the lack of clinical or experimental data on the impact of radiation on gut microbiota, a prospective observational study of gut microbiota was performed in gynecological cancer patients receiving pelvic radiotherapy. In the current study, the overall composition and alteration of gut microbiota in cancer patients receiving radiation were investigated by 454 pyrosequencing. Gut microbial composition showed significant differences (P < 0.001) between cancer patients and healthy individuals. The numbers of species-level taxa were severely reduced after radiotherapy (P < 0.045), and the abundance of each community largely changed. In particular, the phyla Firmicutes and Fusobacterium were significantly decreased by 10% and increased by 3% after radiation therapy, respectively. In addition, overall gut microbial composition was gradually remolded after the full treatment course of pelvic radiotherapy. In this set of cancer patients, dysbiosis of the gut microbiota was linked to health status, and the gut microbiota was influenced by pelvic radiotherapy. Although further studies are needed to elucidate the relationship between dysbiosis and complications induced by pelvic radiotherapy, the current study may offer insights into the treatment of cancer patients suffering from complications after radiation therapy.     

Intrafraction esophageal motion in patients with clinical T1N0 esophageal cancer

Aim

To investigate the intrafraction movement of the esophagus using fiducial markers.

Evaluation of the motion of lung tumors during stereotactic body radiation therapy (SBRT) with four-dimensional computed tomography (4DCT) using real-time tumor-tracking radiotherapy system (RTRT)

PurposeWe investigated the usefulness of four-dimensional computed tomography (4DCT) performed before stereotactic body radiation therapy (SBRT) in determining the internal margins for peripheral lung tumors.Methods and MaterialsThe amplitude of the movement of a fiducial marker near a lung tumor measured using the maximum intensity projection (MIP) method in 4DCT imaging was acquired before the SBRT (Amp_CT) and compared with the mean amplitude of the marker movement during SBRT (Amp_mean) and with the maximum amplitude of the marker movement during SBRT (Amp_max) using a real-time tumor-tracking radiotherapy (RTRT) system with 22 patients.ResultsThere were no significant differences between the means of the Amp_mean and the means of the Amp_CT in all directions (LR, P = 0.45; CC, P = 0.80; AP, P = 0.65). The means of the Amp_max were significantly larger than the means of the Amp_CT in all directions (LR, P < 0.01; CC, P = 0.03; AP, P < 0.01). In the lower lobe, the mean difference of the Amp_CT from the mean of the Amp_max was 5.7 ± 8.0 mm, 12.5 ± 16.7 mm, and 6.8 ± 8.5 mm in the LR, CC, and AP directions, respectively.ConclusionsAcquiring 4DCT MIP images before the SBRT treatment is useful to establish the mean amplitude for a patient during SBRT but it underestimates the maximum amplitude during actual SBRT. Caution must be paid to determine the margin with the 4DCT especially for tumors at the lower lobe where it is of the potentially greatest benefit.     

Incidence of radiation toxicity in cervical cancer and endometrial cancer patients treated with radiotherapy alone versus adjuvant radiotherapy

AimThe study was made to evaluate early and late toxicity in a diversified group of patients receiving definitive or adjuvant radiotherapy in terms of clinical diagnosis and treatment methods.BackgroundRadiotherapy is a standard way of treatment in cervical and endometrial cancer patients, both as definitive and adjuvant therapy. But every radiation treatment may be involved with toxicity.Materials and methodsA detailed analysis was performed of 263 patients with gynaecological cancer treated with definitive (90 patients with cervical cancer received radiochemotherapy or radiotherapy exclusively) and adjuvant radiotherapy (38 with cervical and 135 with endometrial cancer).ResultsAcute reactions were found in 51.3% and late reactions were found in 14.8% of patients. It was stated that early (p < 0.007) and late (p < 0.003) post radiation reaction appear more frequently in women treated with definitive than adjuvant radiotherapy. The analysis of the whole group revealed higher rate of toxicity, both early and late, in the gastrointestinal tract than in the urinary system (p < 0.004). Comparing the subgroups, it was found that intestinal reactions occurred more frequently in the definitive radiotherapy group than in the adjuvant one.The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of radiotherapy. The comparison of the subgroups showed that interruptions occurred more frequently in patients receiving definitive rather than adjuvant radiotherapy (17.7–2.9%).ConclusionsDefinitive radiotherapy compared with adjuvant treatment may by associated with higher percentage of side effects caused by dose of therapy and correlation with chemotherapy.     

Radiation injury of the parotid glands during treatment for head and neck cancer: assessment using dynamic contrast-enhanced MR imaging

The parotid gland is an important organ at risk of complications of radiotherapy for head and neck cancer. In this study, we examined the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessment of radiation injury to the parotid glands. DCE-MRI was performed before and 3 months after radiotherapy in patients treated for head and neck cancer. DCE-MRI was analyzed using the pharmacokinetic model proposed by Tofts and Kermode to produce three DCE parameters: k(trans), v(e) and v(p). These parameters were correlated with the dose of radiation delivered to the parotid glands and the degree of radiation-induced parotid atrophy. The mean radiation dose received by the parotid glands was 47.1 ± 6.6 Gy. All patients received concurrent chemotherapy. There was a significant rise in all three parameters after therapy (P < 0.0001). Baseline v(e) and v(p) and the post-treatment rise in v(e) correlated with parotid gland atrophy (P = 0.0008, 0.0003 and 0.0022, respectively). DCE-MRI has the potential to be used as a non-invasive technique for predicting and assessing radiation injury in the parotid glands.     

Special stereotactic radiotherapy techniques: procedures and equipment for treatment simulation and dose delivery

Stereotactic radiotherapy (SRT ) is a multi-step procedure with each step requiring extreme accuracy. Physician-dependent accuracy includes appropriate disease staging, multi-disciplinary discussion with shared decision-making, choice of morphological and functional imaging methods to identify and delineate the tumor target and organs at risk, an image-guided patient set-up, active or passive management of intra-fraction movement, clinical and instrumental follow-up. Medical physicist-dependent accuracy includes use of advanced software for treatment planning and more advanced Quality Assurance procedures than required for conventional radiotherapy. Consequently, all the professionals require appropriate training in skills for high-quality SRT.Thanks to the technological advances, SRT has moved from a “frame-based” technique, i.e. the use of stereotactic coordinates which are identified by means of rigid localization frames, to the modern “frame-less” SRT which localizes the target volume directly, or by means of anatomical surrogates or fiducial markers that have previously been placed within or near the target. This review describes all the SRT steps in depth, from target simulation and delineation procedures to treatment delivery and image-guided radiation therapy. Target movement assessment and management are also described.     

Bladder Cancer After Radiotherapy for Prostate Cancer

External beam radiotherapy (EBRT) is frequently used in the management of prostate cancer (PCa) as definitive, postoperative, or salvage local treatment. Although EBRT plays a central role in the management of PCa, complications remain a troubling by-product. Several studies have demonstrated an association between radiotherapy and elevated risk of acute and late toxicities. A secondary malignancy induced by initial therapy represents one of the most serious complications related to definitive cancer treatment. The radiation-related secondary primary malignancy risk increases with increasing survival time. Transitional cell carcinoma of the bladder is the most frequent secondary primary malignancy occurring after radiotherapy and is described as more aggressive; it may be diagnosed later because some radiation oncologists believe that the hematuria that occurs after prostate EBRT is normal. Some patients treated for localized PCa will subsequently develop invasive bladder cancer requiring surgical intervention. Patients with PCa treated with EBRT should be monitored closely for the presence of bladder cancer.Key words: Bladder cancer, Prostate cancer, Radiotherapy, External beam radiotherapyThe phenomenon of radiation-inducing the carcinogenesis has been well described in literature for decades. The correlation between ionizing radiation and DNA damage has been discussed in several studies.^1–4 Most of these studies evaluated the growth of solid tumors in a large population exposed to moderate to heavy doses of radiation, such as factory workers, patients exposed to a large number of diagnostic radiographic studies, and survivors of atomic and nuclear explosions. ¹ The casual effects of radiation exposure with subsequent mutagenesis are quite clear, shown both in vivo and in vitro.² Previous radiotherapy (RT) for prostate cancer (PCa) may play an important role in the development of secondary primary bladder cancer. This is a fairly uncommon event but a very real entity, of which both urologists and radiation oncologists need to be aware.     

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.     

The impact of local control timing in Ewing sarcoma

AimTo assess the impact of delay in local control on survival outcomes of Ewing sarcoma (ES) patients.BackgroundThe cornerstone of therapy of localized ES includes chemotherapy and local control with surgery or radiotherapy. We sought to assess the impact of delay (>15 weeks) in timing of local control on survival outcomes of ES patients.MethodsData of consecutive patients with primary non-metastatic ES of the extremities, treated at a single institution were collected. The impact of delay of timing for local control, demographics, and disease characteristics on overall survival (OS) was analyzed.ResultsA total of 43 patients with ES of the extremity were included. All patients received neoadjuvant chemotherapy. Local control was by surgery in 36 patients and definitive radiation in 7. A total of 16 patients had delay in local control. At a median follow of up of 48 months, patients with delay in local control had significantly inferior OS compared to those with optimal local control timing (5-year OS 56% vs. 80%, respectively, p = 0.044). Other factors that predicted inferior OS included definitive radiation as opposed to definitive surgery (5-year OS 25% vs. 79%, respectively, p = 0.041) and tumor necrosis <90% as opposed to ≥90% (5-year OS 55% vs. 90%, respectively, p = 0.01).ConclusionDelay in definitive therapy, local control with radiation as opposed to surgery and poor post-chemotherapy tumor necrosis predict inferior OS in ES. Adopting strategies to minimize delay in local control could improve survival outcomes.     

Impact of rotational errors of whole pelvis on the dose of prostate-based image-guided radiotherapy to pelvic lymph nodes and small bowel in high-risk prostate cancer

BackgroundThe target volume increases when the prostate and pelvic lymph nodes (PLNs) are combined, and the fiducial markers (FMs) are placed at the edge of the irradiation field. Thus, the position of FMs may be changed by the rotational errors (REs) of “whole pelvis”. The aim of this study was to examine the impact of REs of “whole pelvis” on the dose of FMs-based image-guided radiotherapy to the PLNs and the small bowel in prostate cancer including the PLNs.Materials and methodsWe retrospectively evaluated 10 patients who underwent prostate cancer radiotherapy involving the PLNs. The position of FMs was calculated from the radiographs obtained before and after the 6D correction of pelvic REs. We simulated the delivery dose considering the daily pelvic REs and calculated the difference from the planned dose in the D_98% of the PLN clinical target volume and the D_2cc, and V_45Gy of the small bowel.ResultThe position of FMs strongly correlated with the pelvic REs in the pitch direction (r = 0.7788). However, the mean delivered doses to PLNs for 10 patients were not significantly different from the planned doses (p = 0.625). Although the D_2cc and V_45Gy of the small bowel strongly correlated with the pitch rotation of the pelvis, there was no significant difference between the delivered and planned doses (p = 0.922 and p = 0.232, respectively).ConclusionThe dosimetric effect of pelvic REs on the dose to PLNs and the small bowel was negligible during the treatment course.     

Minimizing the potential of cancer recurrence and metastasis by the use of graphene oxide nano-flakes released from smart fiducials during image-guided radiation therapy

An increasing number of studies show that cancer stem cells become more invasive and may escape into blood stream and lymph nodes before they have received a lethal dose during radiation therapy. Recently, it has been found that graphene oxide (GO) can selectively inhibit the proliferative expansion of cancer stem cells across multiple tumor types. In this study, we investigate the feasibility of using GO during radiotherapy to synergistically inhibit cancer stem cells, and lower the risk of cancer metastasis and recurrence. We hypothesize that graphene oxide nano-flakes (GONFs) released from newly-designed radiotherapy biomaterials (fiducial) can reach targeted tumor cells within 14–21 days. These are the typical time periods between the implantation of the fiducial and the start of image-guided radiation therapy. To test this hypothesis, the spatial-temporal diffusion of GONFs in soft tissue is investigated as a function of different particle sizes. Toxicity of GONFs to normal (HUVEC) and cancer (A549) cells has been assessed using the MTT assay. In addition, the survival fraction of A549 cells treated with GONFs is determined via clonogenic assay during radiotherapy. The diffusion study shows that only GONFs sizes of 50 and 200 nm could achieve the desired concentration of 50 μg/mL for 2 cm diameter tumor after 14 and 21 days respectively. The clonogenic and the MTT assay confirm the additional benefit of GONFs in killing lung cancer cells during radiotherapy. This work avails ongoing in vivo studies that use GONFs to enhance the treatment outcome for cancer patients during radiation therapy.