Fractional Delivery Research Articles

Leading Practice: Implementation of an Innovative Approach to Rapid Breast Radiotherapy

Whole breast radiotherapy (RT) is a standard management approach in early-stage breast cancer post-lumpectomy. Typically, the multi-step planning process requires wait-times varying from a few days to weeks. At our institution, the Clinical Specialist Radiation Therapist (CSRT) role has arisen as an integral part of an inter-professional team. The breast CSRT functions within the RT on-treatment reviews to assess and manage patient side effects and completes target volume delineation in select early-stage patients. The CSRT role development and validation occurred in parallel to the technological development of automated treatment planning software, which reduces multi-levels of manual planning. The incorporation of new models of care and technological innovation enable the development of a rapid breast RT process. The QuickStart program was developed with the goal to shorten wait-times for whole breast RT. Patients treated through this program have CT simulation, treatment planning and delivery of the first treatment fraction within 24 hours. The streamlined process is led by the advanced practice CSRT, who is responsible for all essential activities required to expedite the planning process, including upfront coordination of CT and treatment times, target delineation, and ongoing communication with the team and patient. The CSRT’s involvement in target delineation for the oncologist’s review and approval allows for increased workload flexibility of the radiation oncologists, enabling them to dedicate time to other complex medical issues and the provision of additional patient care activities. This furthers more efficient and cost-effective models of care. Initial results from a clinical study showed that women treated through QuickStart process received their first treatment 11 days in advance of similar patients treated through the standard process. Departmental quality control checks performed prior to the initiation of RT treatment did not detect any clinical or technical deficiencies in any of the plans. Independent peer-review of each plan in Quality Assurance rounds demonstrated 100% compliance with the departmental protocol. The QuickStart process effectively shortened the wait interval between patient consultation to the initiation of RT treatment and allowed patients to be treated well before the 14-day wait-time standards endorsed by Cancer Care Ontario. Since its inception, the program continues to be expanded to accommodate more patients. To date, more than 340 patients have been treated through this streamlined process. The QuickStart program helps to ensure patients have timely access to high quality care while enabling providers to: collaborate, further best practices, maintain a manageable workload and optimize the use of healthcare resources in a sustainable manner. By aligning the roles within a multidisciplinary team and leveraging technology, patient wait times can be reduced considerably. This innovative model of care offers breast cancer patients the same high quality and effective RT without a delay. Currently, the CSRT is training treatment planners to contour the post-operative cavity to further increase access to this process. Identification of the organizational enablers required for the Breast QuickStart process will enable the development of new models of care within other multi-disciplinary radiation oncology disease sites.

Injection of SVF combined with HBO2 improves viability of unfavorably designed flaps

Soft-tissue reconstruction is complicated by ischemia and reperfusion injury. Animal trials have documented the independent healing benefits of hyperbaric oxygen preconditioning (HBOP) and stem cell delivery in cutaneous flaps. We explored the role of HBOP and stem cell delivery in flap preconditioning and survival. We designed a randomized controlled trial to assess the effects of hyperbaric oxygen preconditioning and stromal vascular fraction (SVF) delivery on flap survival. Of the first 24 guinea pigs, six received neither HBOP nor injections, and six underwent HBOP without injections. Of the remaining 12 animals, six received SVF or saline injections in the absence of HBOP. The final six animals received autologous SVF injections or saline injections followed by four HBOP treatments. To enhance clinical relevance, a group of 6 animals underwent HBOP prior to SVF or saline injections. Thereafter, an unfavorably designed cutaneous flap was elevated and assessed via study-blinded observer, as well as by quantification of TUNEL-positive cells. Distal necrosis of the tissue flap was more extensive in the no-intervention group (45% of flap). Flaps treated with HBOP only and those treated with SVF injections demonstrated only 38.2% and 27.1% distal necrosis. The most significant difference occurred in the combination HBOP and SVF group, where distal necrosis was only 21.1% of the flap (p ≤ 0.05). SVF delivery immediately prior to flap elevation further minimized distal necrosis of the flap to 15.6%. These findings were mirrored by the TUNEL assay. Combining HBOP and SVF improves flap viability.

Development and Evaluation of Terminalia Arjuna Loaded Phytosome for Bioavailability Enhancement

Present work was aimed to develop and investigate phosphatidylcholinatedphytosome system based on triterpenoid fraction of Terminalia Arjuna (TFTA) for secure and efficient delivery of triterpenoid to enhanced bioavailability. Microwave-assisted extraction (MAE) a green method with a significant reduction in extraction time and organic solvent consumption has been selected and successful extraction of triterpenoids with good yield. Planterosomes a novel carrier for drug delivery of triterpenoid fraction of Terminalia Arjuna were effectively fabricated with a specified molar ratio of 7:3 of TFTA-PC complex and cholesterol in chloroform: methanol (3:1) by the thin layer film hydration method and examined for particle size, zeta potential, drug entrapment efficiency, scanning electron microscopy, FTIR and differential scanning calorimetry study. Formulation of planterosomes showed a narrow size distribution with an average diameter of 381.2 ± 1.82 nm. The entrapment efficiency (EE) of TFTA was 87.94 ± 0.41%. Release study demonstrated prolonged triterpenoid release from phytosomes following higuchi release kinetics with r2 = 0.995. Ex-vivo permeation studies demonstrated the presence of significant absorption of TFTA-PC complex as compared to the TFTA and thereby, the superiority of complex which may be due to the amphiphilic nature of complex which greatly enhance the lipid miscibility of TFTA. From stability studies it was conclude that drug leakage was not significant at storage condition which suitable for vesicles. Conclusively, TFTA loaded planterosomes might be an efficient carrier for triterpenoids which enhance the absorption triterpenoids across the biological membrane for effective management of curing various diseases. 

Estuarine abandoned channel sedimentation rates record peak fluvial discharge magnitudes

Fluvial sediment deposits can provide useful records of integrated watershed expressions including flood event magnitudes. However, floodplain and estuarine sediment deposits evolve through the interaction of watershed/marine sediment supply and transport characteristics with the local depositional environment. Thus extraction of watershed scale signals depends upon accounting for local scale effects on sediment deposition rates and character. This study presents an examination of the balance of fluvial sediment dynamics and local scale hydro-geomorphic controls on alluviation of an abandoned channel in the Salinas River Lagoon, CA. A set of three sediment cores contained discrete flood deposits that corresponded to the largest flood events over the period of accretion from 1969 to 2007. Sedimentation rates scaled with peak flood discharge and event scale sediment flux, but were not influenced by longer scale hydro-meteorological activities such as annual precipitation and water yield. Furthermore, the particle size distributions of flood deposits showed no relationship to event magnitudes. Both the responsiveness of sedimentation and unresponsiveness of particle size distributions to hydro-sedimentological event magnitudes appear to be controlled by aspects of local geomorphology that influence the connectivity of the abandoned channel to the Salinas River mainstem. Well-developed upstream plug bar formation precluded the entrainment of coarser bedload into the abandoned channel, while Salinas River mouth conditions (open/closed) in conjunction with tidal and storm surge conditions may play a role in influencing the delivery of coarser suspended load fractions. Channel adjacent sediment deposition can be valuable records of hydro-meteorological and sedimentological regimes, but local depositional settings may dominate the character of short term (interdecadal) signatures.

Estimation of intra-arterial chemotherapy distribution to the retina in pediatric retinoblastoma patients using quantitative digital subtraction angiography.

Background and purpose The purpose of this article is to estimate the distribution of superselective intra-arterial chemotherapy (IAC) delivery to ocular target tissue using quantitative digital subtraction angiography (qDSA). Materials and methods From March 2010 to January 2016, 50 ophthalmic artery contrast DSAs obtained immediately prior to IAC infusions in 22 patients were analyzed. This study was conducted under a retrospective review IRB (no. 10-01862). Parametric color-coded DSAs (iFlow, Siemens Medical) were post-processed (MATLAB, The Mathworks Inc.) using two methods: two box regions of interest (pre-retina and globe) and four custom regions of interest (ROIs-ophthalmic artery, choroid, supraclinoid internal carotid artery (ICA), cavernous ICA). Mean interobserver reliability of custom ROI selection is presented as a 95% confidence interval of interclass correlation, and fractional chemotherapy delivery to selected ROIs as means ± standard deviation in this study. Results The estimated fraction of chemotherapy delivered to the globe with the first method was 79.5%. Percentage regional delivery using the second method was as follows: ophthalmic artery, 85.8%; choroid, 60.5%; supraclinoid ICA, 14.2%. The cavernous ICA ROI (encompassing distal catheter and potential reflux) gave a signal equivalent to 9.3% of total delivery. Conclusion Parametric color-coded qDSA can estimate the fraction of IAC delivered to the retina and other orbital structures in ocular retinoblastoma patients. This information can inform delivery location and dosing strategies on a patient-specific basis.

Pediatric dermatology procedures and pearls: Multimodal revision of earlobe keloids.

Keloid scars are benign proliferations of fibrous tissue and collagen that usually occur in response to cutaneous injury. Many treatment modalities have been described in the literature, with variable rates of recurrence and no clear consensus. Keloids remain a therapeutic challenge to patients and physicians alike. Herein we describe a novel technique for treating recurrent earlobe keloids in an outpatient setting with multimodal therapy including shave removal followed immediately by ablative fractional laser resurfacing (AFR) and laser-assisted delivery (LAD) of corticosteroids.

Short-pulsed laser for the treatment of tattoos, pigmented lesions, scars and rejuvenation.

This review describes the use of picosecond lasers for the treatment of tattoos, pigmented lesions, scars, and their use in rejuvenation. These devices have delivered enhanced efficacy for the treatment of tattoos and pigmented lesions when compared to the older 40-50 nanosecond devices. The fractional delivery with the picosecond devices have opened up a new method of rejuvenation for photodamaged skin and the treatment of scars. The delivery of these high-energy short pulses have created zones of injury in the skin referred to as areas of laser-induced optical breakdown. These areas of damage appear to produce cytokines and chemokines which result in epidermal and dermal repair and remodeling. The dual use of these devices with the flat and the fractional optics have made these devices useful in many ways that have been unanticipated.

Opportunities for laser-assisted drug delivery in the treatment of cutaneous disorders.

Fractional laser-assisted drug delivery (LADD) is increasingly finding its way into clinical practice as a new means to enhance topical drug uptake and improve treatment of cutaneous disorders. To date, LADD has been used for a wide range of conditions, including photodamaged skin, neoplastic lesions, scars, cutaneous infections, and vitiligo as well as for topical anesthetic and aesthetic procedures. Substantiated by randomized controlled clinical trials, strong evidence is available for LADD's usefulness for photodynamic therapy (PDT), for which improved efficacy using laser-assisted photosensitizer treatment is established for actinic keratosis compared with conventional PDT. Over time, the modality has undergone increasing refinement and offers the potential advantages of reduced treatment durations, shortened incubation times, and the replacement of cumbersome, patient-dependent treatment regimens with quick, in-office procedures. Notwithstanding, LADD is still a new enhancement technique, and risks of both local and systemic adverse events are insufficiently explored. With conscientious development, however, LADD promises to improve existing regimens and make new pharmacological treatments a reality for a wide range of cutaneous disorders.

Evaluation of Gross Tumor Volume Changes Prior to the First Delivered Fraction in Primary and Metastatic Lung Tumors Treated By Stereotactic Body Radiation Therapy: Does Time from Simulation to Start Matter?

To quantify potential volumetric discrepancies in gross tumor volume (GTV) from time of simulation to the delivery of the first radiation fraction and to identify predictors of size change for patients with primary and metastatic lung tumors treated by image-guided stereotactic body radiotherapy (SBRT). The cone beam computed tomography (CBCT) scan obtained at the first fraction of radiation for 14 primary early-stage non-small cell lung cancer tumors and 10 metastatic lung tumors treated with thoracic SBRT were rigidly registered to the initial computed tomography (CT) scans obtained at simulation. All patients were treated with four-dimensional CT (4DCT)-based image-guided 3-5 fraction SBRT using abdominal compression and body-fixation. The GTV was delineated on both the mean intensity projection (MeanIP) data set of the CT simulation scan and the CBCT scan, and percent change in GTV volume was calculated from time of CT simulation to first fraction of treatment. The most common prescription dose and fractionation regimen was 50 Gy in 5 fractions (n = 21). The fraction size ranged from 8 to 18 Gy (median, 10 Gy). The correlation between percentage GTV change and treatment variables, tumor characteristics, and clinical outcome (median 45 months, range 25 to 77 months) were statistically evaluated using linear regression to test significance. The median patient age was 72 years (range, 43 to 90 years). GTV and planning target volume (PTV) were 7.8 cc (range, 0.8 to 53.8 cc), and 31.2 cc (range, 7.5 to 118.2 cc), respectively. For all treated tumors, GTV increased a median of 19.9% (range, -4.4 to 45.9%) over a median time interval of 13 days (range, 2 to 39 days). When stratified according to tumor status, primary lung tumors exhibited a median percent GTV change of 16.2% (range, -4.4 to 39.49%), and metastatic lung tumors GTV size increased a median of 23.4% (range, -3.7 to 45.9 %). The degree of percentage GTV change was inversely related to initial tumor volume on CBCT scan for all treated tumors (P = 0.004). The observed change in GTV volume and treatment interval for all tumors approached significance (P = 0.07) with tumors treated less than or equal to 10 days exhibiting smaller % change in volume compared to those treated after 10 days. Right sided lung tumors were more likely to experience increase in GTV size (P = 0.03). Primary vs. metastatic status, histology, and central vs. peripheral tumor location did not correlate with observed tumor volume change (P > 0.05). Degree of GTV change did not correlate with clinically observed local control rates (P > 0.05). Target localization during SBRT is critical, and our results emphasize the value for accurate image guidance techniques for all thoracic tumors treated with hypofractionated courses, particularly in smaller tumors in which larger changes gross tumor volume may be observed. Decreasing time interval from CT simulation to first fraction to 10 days or less may minimize the degree of volumetric tumor change.

Impact of Prolonged Fraction Delivery Time Modelling Stereotactic Body Radiation Therapy with High Dose Hypofractionation on the Killing of Cultured ACHN Renal Cell Carcinoma Cell Line.

Stereotactic body radiotherapy delivers hypofractionated irradiation with high dose per fraction through complex treatment techniques. The increased complexity leads to longer dose delivery times for each fraction. The purpose of this study is to investigate the impact of prolonged fraction delivery time with high-dose hypofractionation on the killing of cultured ACHN cells. The radiobiological characteristics and repair half-time of human ACHN renal cell carcinoma cell line were studied with clonogenic assays. A total dose of 20 Gy was administered in 1, 2 or 3 fractions over 15, 30 or 45 min to investigate the biological effectiveness of radiation delivery time and hypofractionation. Cell cycle and apoptosis analysis was performed after 3-fraction irradiation over 30 and 45 min. The α/β and repair half-time were 5.2 Gy and 19 min, respectively. The surviving fractions increased with increase in the fraction delivery time and decreased more pronouncedly with increase in the fraction number over a treatment period of 30 to 45 min. With increase in the total radiation time to 30 and 45 min, it was found that with the same total dose, 2- and 3-fraction irradiation led to more cell killing than 1-fraction irradiation. 3-fraction radiation induced G2/M arrest, and the percentage of apoptotic cells decreased when the fraction delivery time increased from 30 min to 45 min. Our findings revealed that sublethal damage repair and redistribution of the cell cycle were predominant factors affecting cell response in the prolonged and hypofractionated irradiation regimes, respectively.

The influence of radiotherapy on ceruloplasmin and transferrin in whole blood of breast cancer patients

Ceruloplasmin and transferrin are proteins which play a potential role in the process of breast cancer development. These molecules contain Cu2+ (ceruloplasmin) or Fe3+ ions (transferrin) and thus constitute paramagnetic centers, which can be studied using electron paramagnetic resonance method. The aim of the study was to determine how paramagnetic centers in whole blood of breast cancer patients change under the influence of radiation therapy. Samples of whole blood were taken from 17 women with breast cancer treated with radiotherapy. The measurements were carried out at 170 K using X-band electron paramagnetic resonance (EPR) spectrometer Bruker EMX-10. Two distinct EPR lines, derived from high-spin Fe3+ in transferrin and Cu2+ from ceruloplasmin, were revealed in all frozen samples. The amplitude and integrated intensity of the EPR signal from Cu2+ in ceruloplasmin significantly decreased in all patients after the delivery of the radiation fraction. When comparing the integral intensity of the signal from Fe3+ in transferrin, three different situations were identified which are patient specific: a significant increase, an insignificant change, or a significant decrease after the irradiation. A decreased level of Cu2+ from ceruloplasmin in patients after radiotherapy means a low level of ceruloplasmin in the plasma or an increased content of reduced Cu+ ions. Differences in the integrated intensity of the EPR signal from transferrin translate directly into the amount of bound iron. The observed changes could indicate how well the organism fights against cancer and how easily it adapts to the situation of biochemical stress.

Vaccine vial stopper performance for fractional dose delivery of vaccines

ABSTRACTShortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced—or fractional—doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery.

Stereotactic body radiation therapy for liver metastasis – The linac-based Greater Poland Cancer Centre practice

AimThe main purpose of this work is to give a technical description and present the properties of the liver SBRT protocol implemented in the Greater Poland Cancer Centre (GPCC) in Poznan, Poland. BackgroundStereotactic body radiation therapy (SBRT) for liver metastasis is a non-invasive therapeutic option which enables irradiation of a small target in the body with a high dose. Materials and methodsThis study presents details of our linac-based liver SBRT protocol. Special emphasis has been placed on fiducial implantation, patient preparation (CT scanning, immobilization), treatment planning, and its implementation. ResultsThe liver SBRT treatment course implemented in the GPCC consists of three fractions to deliver a total of 45Gy. Fraction delivery details with description of patient positioning (localization of liver metastasis) are presented below. ConclusionsThe literature validation of the assumptions concerning the steps of the GPCC linac-based liver SBRT procedure show their potential for an effective and patient friendly implementation.

Fractional laser-assisted percutaneous drug delivery via temperature-responsive liposomes

Liposomes are used for transdermal delivery of drugs and vaccines. Our objective was to develop temperature-responsive (TR) liposomes to achieve temperature-dependent, controlled release of an encapsulated drug, and use fractional laser irradiation to enhance transdermal permeability of these liposomes. TR-liposomes prepared using a thermosensitive polymer derived from poly-N-isopropylacrylamide, N,N-dimethylacrylamide, egg phosphatidylcholine, and dioleoylphosphatidylethanolamine, delivered fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as a model drug. Effect of temperature on liposome size and drug release rate was estimated at two temperatures. Transdermal permeation through hairless mouse skin, with and without CO2 fractional laser irradiation, and penetration into Yucatan micro-pig skin were investigated using Franz cell and fluorescence microscopy. Dynamic light scattering showed that mean liposome diameter nearly doubled from 190 to 325 nm between 37 and 50 °C. The rate and amount of OVA-FITC released from TR-liposomes were higher at 45 °C that those at 37 °C. Transdermal permeation of OVA-FITC across non-irradiated skin from both TR- and unmodified liposomes was minimal at 37 °C, but increased at 45 °C. Laser irradiation significantly increased transdermal permeation of both liposome groups at both temperatures. Fluorescence microscopy of frozen biopsy specimens showed deeper penetration of FITC from unmodified liposomes compared to that from polymer-modified liposomes. Rhodamine accumulation was not observed with polymer-modified liposomes at either temperature. Temperature-dependent controlled release of an encapsulated drug was achieved using the TR-liposomes. However, TR-liposomes showed lower skin permeability despite higher hydrophobicity. Fractional laser irradiation significantly increased the transdermal permeation. Additional studies are required to control liposome size and optimize transdermal permeation properties.

Fractional Delivery: Toward a Painless, Safe and Effective Cutaneous Vaccination

Fractional Delivery: Toward a Painless, Safe and Effective Cutaneous Vaccination

Particle size affects the cytosolic delivery of membranotropic peptide-functionalized platinum nanozymes.

Delivery of therapeutic agents inside the cytosol, avoiding the confinement in endo-lysosomal compartments and their degradative environment, is one of the key targets of nanomedicine to gain the maximum remedial effects. Current approaches based on cell penetrating peptides (CPPs), despite improving the cellular uptake efficiency of nanocarriers, have shown controversial results in terms of intracellular localization. To elucidate the delivery potential of CPPs, in this work we analyzed the role of the particle size in influencing the ability of a membranotropic peptide, namely gH625, to escape the endo-lysosomal pathway and deliver the particles in the cytosol. To this aim, we carried out a systematic assessment of the cellular uptake and distribution of monodisperse platinum nanoparticles (PtNPs), having different diameters (2.5, 5 and 20 nm) and citrate capping or gH625 peptide functionalization. The presence of gH625 significantly increased the amount of internalized NPs in human cervix epithelioid carcinoma cells, as a function of particle size. However, scanning transmission electron microscopy (STEM) and electron tomography (ET) revealed a prevalent confinement of PtNPs within vesicular structures, regardless of the particle size and surface functionalization. Only in the case of the smallest 2.5 nm particles, the membranotropic peptide was able to partly maintain its functionality, enabling cytosolic delivery of a small fraction of internalized PtNPs, though particle agglomeration in culture medium limited single-particle transport across the cell membrane. Interestingly, membrane crossing by 2.5 nm functionalized-PtNPs seemed to occur by diffusion through the lipid bilayer, with no apparent membrane damage. For larger particle sizes (≥5 nm), their hindrance likely blocked the membranotropic mechanism. Combining the enhanced uptake and partial cytosolic delivery promoted by gH625, we were able to achieve a strong improvement of the antioxidant nanozyme function of 2.5 nm PtNPs, decreasing both the endogenous ROS level and its overproduction following an external oxidative insult.

Melanoma: Last call for radiotherapy.

Melanoma is traditionally considered to be a radioresistant tumor. However, radiotherapy and immunotherapy latest developments might upset this radiobiological dogma. Stereotactic radiotherapy allows high dose per fraction delivery, with high dose rate. More DNA lethal damages, less sublethal damages reparation, endothelial cell apoptosis, and finally clonogenic cell dysfunction are produced, resulting in improved local control. Radiotherapy can also enhance immune responses, inducing neoantigens formation, tumor antigen presentation, and cytokines release. A synergic effect of radiotherapy with immunotherapy is expected, and might lead to abscopal effects. If hadrontherapy biological properties seem able to suppress hypoxia-induced radioresistance and increase biological efficacy, ballistic advantages over photon radiations might also improve radiotherapy outcomes on usually poor prognosis locations. The present review addresses biological and clinical effects of high fraction dose, bystander effect, abscopal effect, and hadrontherapy features in melanoma. Clinical trials results are warranted to establish indications of innovative radiotherapy in melanoma.

Fractional laser-assisted topical delivery leads to enhanced, accelerated and deeper cutaneous 5-fluorouracil uptake

ABSTRACTBackground: Topical 5-Fluorouracil (5-FU) exhibits suboptimal efficacy for non-melanoma skin cancer, attributed to insufficient intracutaneous penetration. This study investigates the impact of ablative fractional laser (AFXL) at different laser-channel depths on cutaneous 5-FU pharmacokinetics and biodistribution.Methods: In vitro porcine skin underwent AFXL-exposure using a fractional 10,600 nm CO2-laser, generating microscopic ablation zones (MAZ) reaching the dermoepidermal junction (MAZ-ED), superficial-(MAZ-DS), or mid-dermis(MAZ-DM). 5-FU in AFXL-exposed and control skin was measured in Franz diffusion cells at 4 and 24 hours (n = 55). HPLC quantified 5-FU in full-thickness skin, specific skin depths of 100μm-1500μm, and transcutaneous receiver-compartments. Qualitative matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) visualized 5-FU in selected samples.Results: Overall, AFXL enhanced and accelerated 5-FU uptake versus unexposed controls, with increased accumulation in deep skin layers (p < 0.01). While total, 24-hour 5-FU uptake in control skin was 0.096 mg/cm3 (0.19% of applied concentration), AFXL delivered up to 4.707 mg/cm3 (MAZ-DM; 9.41% uptake, 49-fold enhancement) (p = 0.002; 24 hours). Indicating accelerated delivery, 5-FU in laser-exposed samples at 4 hours was at least 10-fold that of 24-hour controls (p = 0.002). Deeper laser-channels increased delivery throughout the skin (MAZ-ED vs. MAZ-DM; p<0.01). MALDI-MSI confirmed enhanced, accelerated, deeper and more uniform 5-FU distribution after AFXL versus controls.Conclusions: AFXL offers laser-channel depth-dependent, enhanced and accelerated 5-FU uptake, with increased deposition in deep skin layers.

Peer Review of Radiotherapy Planning: Quantifying Outcomes and a Proposal for Prospective Data Collection

AimsThe Canadian Partnership for Quality Radiotherapy quality assurance guidelines recommend that radiation oncologist peer review of curative radiotherapy plans takes place ideally before the first fraction of treatment is delivered. This study documented and evaluated the outcomes of weekly, disease site-specific, radiotherapy peer review, quality assurance rounds at the Tom Baker Cancer Centre in Calgary, Canada with a view to making recommendations about the optimal timing and documentation of peer review during the radiotherapy planning processes. Materials and MethodsOutcomes of each case reviewed at (i) breast, (ii) head and neck (including thyroid and cutaneous cases) and (iii) lung team quality assurance rounds from 6 January to 5 May 2015 were recorded prospectively. Each radiotherapy plan was assigned an outcome: A for plans with no suggested changes; B for satisfactory, but where issues were raised to consider for future patients; or C when a change was recommended before the first or next fraction. The B outcomes were further subdivided into B1 for a case-specific concern and B2 for a policy gap. Plans were assessed after contour definition and before the plan was formulated (post-contouring reviews) and/or assessed when the plan was complete (post-planning reviews). Results209 radiotherapy plans prescribed by 20 radiation oncologists were peer reviewed at 43 quality assurance meetings. 93% were curative-intent and 7% were palliative. 83% of plans were reviewed before delivery of the first treatment fraction. There were a total of 257 case reviews: 60 at the post-contouring stage, 197 at the post-planning stage, including 46 patients reviewed at both time points. Overall rates of A, B1, B2 and C outcomes were 78%, 9%, 4% and 9%, respectively. The most common reason for a B or C outcome was related to target volume definition. Only 56% of C outcomes at the post-planning stage would have been detected at the post-contouring stage. Results varied between tumour site groups. Conclusions9% of radiotherapy plans reviewed had changes suggested before delivery to the patient. Review at the post-planning stage after plan completion was necessary to detect all suggested changes, but for head and neck cases, all C outcomes could have been detected at the post-contouring stage. More widespread implementation of radiotherapy peer review in the UK is recommended.

Dosimetric impact of different bladder and rectum filling during prostate cancer radiotherapy.

BackgroundThe aim of this study was to analyze the influence of volumetric changes of bladder and rectum filling on the 3D dose distribution in prostate cancer radiotherapy.MethodsA total of 314 cone-beam CT (CBCT) image data sets from 19 patients were enrolled in this study. For each CBCT, the bladder and rectum were contoured and volume sizes were normalized to those on their original CT. The daily delivered dose was recalculated on the CBCT images and the doses to bladder and rectum were investigated. Linear regression analysis was performed to identify the mean dose change of the volume change using SPSS 19.ResultsThe data show that the variances of the normalized volume of the bladder and the rectum are 0.13–0.58 and 0.12–0.50 respectively. The variances of V70Gy, V60Gy, V50Gy, V40Gy and V30Gy of bladder are bigger than those of rectum for 17 patients. The linear regression analysis indicates a 10 % increase in bladder volume will cause a 5.6 % (±4.9 %) reduction in mean dose (p <0.05).ConclusionsThe bladder’s volume change is more significant than that of the rectum for the prostate cancer patient. The rectum volume variations are not significant except for air bubbles, which change the shape and the position of the rectum. The bladder volume variations may cause dose changes proportionately. Monitoring the bladder’s volume before fractional treatment delivery will be crucial for accurate dose delivery.