Impact of different optimization strategies on the compatibility between planned and delivered doses during radiation therapy of cervical cancer

PurposeTo analyse the impact of different optimization strategies on the compatibility between planned and delivered doses during radiotherapy of cervical cancer.Material/methodsFour treatment plans differing in optimisation strategies were prepared for ten cervical cancer cases. These were: volumetric modulated arc therapy with (_OPT) and without optimization of the doses in the bone marrow and for two sets of margins applied to the clinical target volume that arose from image guidance based on the bones (IG(B)) and soft tissues (IG(ST)). The plans were subjected to dosimetric verification by using the ArcCHECK system and 3DVH software. The planned dose distributions were compared with the corresponding measured dose distributions in the light of complexity of the plans and its deliverability.ResultsThe clinically significant impact of the plans complexity on their deliverability is visible only for the gamma passing rates analysis performed in a local mode and directly in the organs. While more general analyses show statistically significant differences, the clinical relevance of them has not been confirmed. The analysis showed that IG(ST)_OPT and IG(B)_OPT significantly differ from IG(ST) and IG(B). The clinical acceptance of IG(ST)_OPT obtained for hard combinations of gamma acceptance criteria (2%/2 mm) confirm its satisfactory deliverability. In turn, for IG(B)_OPT in the case of the rectum, the combination of 2%/2 mm did not meet the criteria of acceptance.ConclusionDespite the complexity of the IG(ST)_OPT, the results of analysis confirm the acceptance of its deliverability when 2%/2 mm gamma acceptance criteria are used during the analysis

Currently used in clinical practice beam rate changes have no significant effect on the reduction of clonogenic capacity of PNT1A cells in vitro

Background: Due to the lack of selectivity of ionizing radiation between normal and cancer cells, it is important to improve the existing radiation patterns. Lowering the risk of cancer recurrence and comfort during treatment are priorities in radiotherapy. Materials and methods: In the experiment we used dose verification to determine the irradiation time calculated by a treatment planning system for 6XFFF and 10XFFF beams. Cells cultured under standard conditions were irradiated with a dose of 2 Gy at different beam rates 400 MU/min, 600 MU/min, 800 MU/min, 1000 MU/min, 1400 MU/min,  1600 MU/min and 2400 MU/min using 6XFFF, 10XFFF and 6XFF beams. Results: The experiment was aimed at comparing the biological response of normal prostate cells after clinically applied radiation patterns. No statistically significant differences in the cellular response were observed. The wide range of beam rates as well as the beam profiles did not significantly affect cell proliferation. Conclusions: High beam rates, without significantly affecting the clonogenic capacity of cells, have an impact on the quality of patient's treatment. With the increasing beam rate the irradiation time is shortened, which has an important impact on patients’ health. This experiment can have a practical significance

Verification of electron beam parameters in an intraoperative linear accelerator using dosimetric and radiobiological response methods

Background: The availability of linear accelerators (linac) for research purposes is often limited and therefore alternative radiation sources are needed to conduct radiobiological research. The National Centre for Radiation Research in Poland recently developed an intraoperative mobile linac that enables electron irradiation at energies ranging from 4 to 12 MeV and dose rates of 5 or 10 Gy/min. The present study was conducted to evaluate the electron beam parameters of this intraoperative linac and to verify the set-up to evaluate out-of-field doses in a water phantom, which were determined through dosimetric and biological response measurements. Materials and methods: The distribution of radiation doses along and across the radiation beam were measured in a water phantom using a semiconductor detector and absolute doses using an ionisation chamber. Two luminal breast cancer cell lines (T-47D and HER2 positive SK-BR-3) were placed in the phantom to study radiation response at doses ranging from 2 to 10 Gy.  Cell response was measured by clonogenic assays. Results and Conclusion: The electron beam properties, including depth doses and profiles, were within expected range for the stated energies. These results confirm the viability of this device and set-up as a source of megavoltage electrons to evaluate the radiobiological response of tumour cells

Results of the IROCA international clinical audit in prostate cancer radiotherapy at six comprehensive cancer centres

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5-87.5% of cases); presentation to multidisciplinary tumour board (2.5-100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42-102.5 days); number of treatment interruptions ≥ 1 day (7.5-97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures

IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits — Training and Education for Standardization

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus-based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits — Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres

EPID-based daily verification of reproducibility of patients’ irradiation with IMRT plans

AimThe aim of the work was to catch potential errors with daily EPID measurements of repeatability of the dose distribution during irradiation of IMRT patients.Materials and methodsIn the first stage, measurements were made using an anthropomorphic phantom in which the method of collecting data with an EPID device and the possibility of detecting errors in positioning were developed. Next, for 23 patients, the pelvis (P) and head and neck (H&N) regions, images were collected with an EPID device for each IMRT subfield daily and compared to reference images using the gamma method (DTA 3mm, DD 3%). Finally, the dependencies between treatment plan parameters, pre-verification results and repeatability of collected images were evaluated.ResultsThe anthropomorphic phantom study has shown what kind of effects we can expect with EPID measured at potential shifts during radiotherapy. For the clinical case, score results were obtained for individual tumor regions as below: (P) 0.786±1.046, (H&N) 0.720±1.552. For most evaluated cases, score values were below 1%: (P) 75.5% and (H&N) 83.9% of analyzed fields. 95% of all evaluated data was with the score below: (P) 2.86% and (H&N) 3.40%. The relationship between the results of the analysis of daily collected images and the results of pre-verification, field size and irradiation time was shown.ConclusionsThe EPID-based daily verification can provide extra information about day-to-day repeatability of treatment, without additional dose

Software simulation of tumour motion dose effects during flattened and unflattened ITV-based VMAT lung SBRT

PurposeRestricted studies comparing different dose rate parameters are available while ITV-based VMAT lung SBRT planning leads to perform the analysis of the most suitable parameters of the external beams used. The special emphasis was placed on the impact of dose rate on dose distribution variations in target volumes due to interplay effects.MethodsFour VMAT plans were calculated for 15 lung tumours using 6 MV photon beam quality (flattening filter FF vs. flattening filter free FFF beams) and maximum dose rate of 600 MU/min, 1000 MU/min and 1400 MU/min. Three kinds of motion simulations were performed finally giving 180 plans with perturbed dose distributions.Results6FFF-1400 MUs/min plans were characterized by the shortest beam on time (1.8 ± 0.2 min). Analysing the performed motion simulation results, the mean dose (Dmean) is not a sensitive parameter to related interplay effects. Looking for local maximum and local minimum doses, some discrepancies were found, but their significance was presented for individual patients, not for the whole cohort. The same was observed for other verified dose metrics.ConclusionsGenerally, the evaluation of VMAT robustness between FF and FFF concepts against interplay effect showed a negligible effect of simulated motion influence on tumour coverage among different photon beam quality parameters. Due to the lack of FFF beams, smaller radiotherapy centres are able to perform ITV-based VMAT lung SBRT treatment in a safe way. Radiotherapy department having FFF beams could perform safe, fast and efficient ITV-based VMAT lung SBRT without a concern about significance of interplay effects

FLASH radiotherapy: an emerging approach in radiation therapy

FLASH radiotherapy (RT) is a technique involving the delivery of ultra-high dose rate radiation to the target. FLASH-RT has been shown to reduce radiation-induced toxicity in healthy tissues without compromising the anti-cancer effects of treatment compared to conventional radiation therapy. In the present article, we review the published data on FLASH-RT and discuss the current state of knowledge of this novel approach. We also highlight the technological constraints and complexity of FLASH-RT and describe the physics underlying this modality, particularly how technology supports energy transfer by ionising radiation (e.g., beam on/off sequence, pulse-energy load, intervals). We emphasise that current preclinical experience is mostly based on FLASH electrons and that clinical application of FLASH-RT is very limited. The incorporation of FLASH-RT into routine clinical radiotherapy will require the development of devices capable of producing FLASH photon beams

Zalecenia Polskiego Towarzystwa Fizyki Medycznej dotyczące kontroli jakości w radioterapii śródoperacyjnej promieniowaniem elektronowym (IOERT) za pomocą mobilnych akceleratorów

Planując i realizując leczenie z użyciem promieniowania jonizującego, należy zapewnić podanie zleconej przez lekarza dawki terapeutycznej, minimalizując równocześnie dawki podane poza objętością tarczową. Osiągnięcie tych dwóch celów w znacznym stopniu zależy od wielkości objętości tarczowej, jej położenia względem narządów krytycznych oraz rodzaju promieniowania użytego do terapii. Charakterystyki głębokościowe powszechnie stosowanych wiązek promieniowania stosowanych w radioterapii pokazują, że szczególnie narażone na pochłonięcie dawki wyższej są tkanki prawidłowe, które położone są na mniejszej głębokości niż tkanki objęte procesem nowotworowym. Dlatego jedną z podstawowych zasad przygotowania leczenia jest taki wybór kierunku napromieniania, aby objętość tarczowa znajdowała się jak najbliżej źródła promieniowania. Realizacja tego celu może zostać osiągnięta poprzez zastosowanie techniki napromieniania śródoperacyjnego, której istotą jest odsunięcie metodami chirurgicznymi tkanek otaczających objętość tarczową od strony wlotowej poza obszar eksponowany na promieniowanie pierwotne i ewentualnie ochrona tkanek znajdujących się dystalnie względem objętości tarczowej. Taka technika określana terminem „radioterapia śródoperacyjna” ma długą historię, ale dopiero w XXI wieku znalazła szersze zastosowanie. Umożliwił to rozwój technologiczny mobilnych urządzeń terapeutycznych oraz zgromadzona wiedza z zakresu radioterapii i radiobiologii. Radioterapia śródoperacyjna znajduje coraz szersze zastosowanie w radioterapii nowotworów głowy i szyi, mięsaków, nowotworów jelita grubego i trzustki [36]. Szczególne znaczenie, głównie z powodów epidemiologicznych, ma radioterapia śródoperacyjna w leczeniu pacjentek z nowotworem piersi [25, 27, 28]

Different levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics.

The implication of the let-7 family in cancer development is multifaceted. The family acts as tumor suppressor miRNA although overexpression of let-7 has also been described in many types of cancer, including head and neck squamous cell carcinoma (HNSCC). The aim of this study includes whether different expression levels of let-7d has an influence on chemo- and radiosensitivity. FaDu cell line models with a gradually increased level of let-7d (models from A to E) were generated with the lentiviral system. Expression levels of pluripotency, chemo-radioresistance/apoptosis, and targets of mRNAs were analyzed by real-time reverse transcription-PCR (qRT-PCR). Radiosensitivity was analyzed using a clonogenic assay after irradiation. Response to cisplatin, 5-FU, doxorubicin, and paclitaxel was done with MTT assay. Statistically significant decrease of K-RAS (p = 0.0369) and CASPASE3 (p = 0.0342) were observed with the growing expression level of let-7d. Cisplatin, 5-FU and doxorubicin caused similar decreased of cell survival with the increase of let-7d level (p = 0.004, post-trend p = 0.046; p = 0.004, post trend p = 0.0005 and p<0.0001, post trend p = 0.0001, respectively). All models were resistant to paclitaxel, irrespective of let-7d expression levels. Only two of the generated models (A and C) were radiosensitive (p = 0.0002). CONCLUSION:the above results indicated that the level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics