Upper rectal fixation with an endorectal balloon in prostate cancer radiotherapy.

Purpose: Despite the efficacy of endorectal balloon (ERB) in reducing rectal radiation dose, the effectiveness of upper rectal fixation remains to be evaluated. The purpose of this study was to evaluate the impact of ERB on upper rectal fixation in patients diagnosed with localized prostate cancer. Materials: Cine MRI was performed in 46 patients with localized prostate cancer to assess the stability of the anterior rectal wall with and without ERB by calculating the standard deviation of the normalized signal intensity at the level of the midgland or the seminal vesicle. Results: The standard deviation of the normalized signal intensity for the anterior rectal wall decreased significantly with the use of ERB both at the level of the midgland (p < 0.05) and the seminal vesicle (p < 0.05). The standard deviation of the anterior rectal wall at the level of the seminal vesicle was significantly higher than at the level of the midgland without ERB (p < 0.05). But with ERB, the standard deviation of the normalized signal intensity at the level of the seminal vesicle became comparable to that at the level of the midgland (p = 0.392). Conclusion: The anterior rectal wall is stabilized by ERBs not only at the level of the midgland but also at the level of the seminal vesicle. ERBs can transform the rectum from a moving and deformable organ into a static and rigid organ.

Treatment outcome of localized prostate cancer using transperineal ultrasound image-guided radiotherapy.

BACKGROUND: We report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT). METHODS: A total of 124 patients (median age: 74 y, 46-84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5-7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76-78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2-3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation. RESULTS: A total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups. CONCLUSION: These results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy.

Optimizing Choice of Skin Surrogates for Surface-Guided Stereotactic Body Radiotherapy of Lung Lesions Using Four-Dimensional Computed Tomography.

Image-guided radiotherapy supported by surface guidance can help to track lower lung lesions' respiratory motion while reducing a patient's exposure to ionizing radiation. However, it is not always clear how the skin's respiratory motion magnitude and its correlation with the lung lesion's respiratory motion vary between different skin regions of interest (ROI). Four-dimensional computed tomography (4DCT) images provide information on both the skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. An analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on the respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing a lower lung lobe lesion, as well as the respiratory motion correlations between the nine ROIs and the TS. The effects of gender and the adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between the ROIs in both the respiratory motion magnitudes and their correlations with the TS have been detected. An overall negative correlation between the ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between the adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. The respiratory magnitudes in regions without rib support tend to be larger for men than for women, but no differences in the ROI-to-TS correlation between sexes have been detected. The described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

Assessing inter and intrafraction uncertainties in adult brain cancer patients using 2D/3D kV and CBCT imaging.

METHOD: 2D/3D kV imaging and CBCT data using 6 degrees of freedom (6DoF) were compared to evaluate inter and intrafraction motion. RESULTS: Results showed that intrafraction errors were low and interfraction levels were within institutional protocols. CONCLUSION: Confidence was given to use low dose 2D/3D kV imaging to confirm daily patient set up errors, and to use pre-treatment CBCT only once weekly for additional imaging information. IMPLICATIONS FOR PRACTICE: Further research is necessary to assess other uncertainties, to enable the calculation of a margin and determining the feasibility of further reduction of this.

Bringing online adaptive radiotherapy to a standard C-arm linac.

Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines.

The First Reported Case of Treating the Ultra-Central Thorax With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR).

Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. He was prescribed 55 Gy in five fractions with CT-STAR. A simulation was performed using four-dimensional CT, and patients were planned for treatment at end-exhale breath-hold. Treatment plans were generated using a strict isotoxicity approach, which prioritized organ at risk (OAR) constraints over target coverage. During treatment, daily CBCTs were acquired and used to generate adapted contours and treatment plans based on the patient's anatomy-of-the-day, all while the patient was on the treatment table. The initial and adapted plans were compared using dose-volume histograms, and the superior plan was selected for treatment. The adapted plan was deemed superior and used for treatment in three out of five fractions. The adapted plan provided improved target coverage in two fractions and resolved an OAR hard constraint violation in one fraction. We report the successful treatment of a patient with ultra-central NSCLC utilizing CT-STAR. This case report builds on previously published in silico data to support the viability and dosimetric advantages of CT-STAR in the ablative treatment of this challenging tumor location. Further data are needed to confirm the toxicity and efficacy of this technique.

Virtual clinical trial-based study for clinical evaluation of projection-reduced low-dose cone-beam CT for image guided radiotherapy.

Purpose: Repeated cone-beam CT (CBCT) scans for image-guided radiotherapy (IGRT) increase the health risk of radiation-induced malignancies. Patient-enrolled studies to optimize scan protocols are inadequate. We proposed a virtual clinical trial-based approach to evaluate projection-reduced low-dose CBCT for IGRT. Materials and methods: A total of 71 patients were virtually enrolled with 26 head, 23 thorax and 22 pelvis scans. Projection numbers of full-dose CBCT scans were reduced to 1/2, 1/4, and 1/8 of the original to simulate low-dose scans. Contrast-to-noise ratio (CNR) values in fat and muscle were measured in the full-dose and low-dose images. CBCT images were registered to planning CT to derive 6-degree-of-freedom couch shifts. Registration errors were statistically analyzed with the Wilcoxon paired signed-rank test. Results: As projection numbers were reduced, CNR values descended and the magnitude of registration errors increased. The mean CNR values of full-dose and half-dose CBCT were >3.0. For full-dose and low-dose CBCT (i.e. 1/2, 1/4 and 1/8 full-dose), the mean registration errors were< ± 0.4 mm in translational directions (LAT, LNG, VRT) and ±0.2 degree in rotational directions (Pitch, Roll, Yaw); the mean magnitude of registration errors were< 1 mm in translation and< 0.5 degree in rotation. The couch shift differences between full-dose and low-dose CBCT were not statistically significant (p>0.05) in all the directions. Conclusion: The results indicate that while the impact of dose-reduction on CBCT couch shifts is not significant, the impact on CNR values is significant. Further validation on optimizing CBCT imaging dose is required.

Transperineal versus transrectal prostate fiducial insertion in radiation treatment of prostate cancer: a systematic review and meta-analysis.

PURPOSE: To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR) approaches, a comprehensive review of observational studies and randomized controlled trials was conducted. This systematic review covered all eligible studies to facilitate a thorough comparison of complications linked to the two fiducial marker insertion methods, TP and TR. METHODS: A comprehensive search of the literature was conducted, encompassing databases such as PubMed, Embase, and the Cochrane Library, up to July 7, 2023. The relative risk and 95% confidence interval were utilized to evaluate the diagnosis and complication rates. RESULTS: The final selection for the methodological quality analysis included 13 observational studies that utilized TP and TR gold fiducial insertion approaches. The meta-analysis revealed significantly lower risks of urinary tract infections (UTI) and rectal bleeding with the TP approach. CONCLUSION: The use of both TP and TR techniques for placing gold seed fiducial markers has proven to be an effective, safe, and well-tolerated method for image-guided radiation therapy in prostate cancer patients. A significant benefit of the TP technique is its ability to avoid rectal puncture, thereby reducing the risk of UTIs. Although the incidence of UTIs and rectal bleeding associated with the TR method is relatively low, these complications can disrupt patient wellbeing and potentially cause delays in treatment.

Intrafraction organ movement in adaptive MR-guided radiotherapy of abdominal lesions - dosimetric impact and how to detect its extent in advance.

INTRODUCTION: Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs. MATERIALS & METHODS: Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future. RESULTS: A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5-10.5 mm) were detected within a median time of 17.1 min (range 1.6-28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement. CONCLUSION: Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.

A novel evaluation model of image registration for cone-beam computed tomography guided lung cancer radiotherapy.

BACKGROUND: The aim of the study was to establish a weighted comprehensive evaluation model (WCEM) of image registration for cone-beam computed tomography (CBCT) guided lung cancer radiotherapy that considers the geometric accuracy of gross target volume (GTV) and organs at risk (OARs), and assess the registration accuracy of different image registration methods to provide clinical references. METHODS: The planning CT and CBCT images of 20 lung cancer patients were registered using diverse algorithms (bony and grayscale) and regions of interest (target, ipsilateral, and body). We compared the coverage ratio (CR) of the planning target volume (PTVCT) to GTVCBCT, as well as the dice similarity coefficient (DSC) of the GTV and OARs, considering the treatment position across various registration methods. Furthermore, we developed a mathematical model to assess registration results comprehensively. This model was evaluated and validated using CRFs across four automatic registration methods. RESULTS: The grayscale registration method, coupled with the registration of the ipsilateral structure, exhibited the highest level of automatic registration accuracy, the DSC were 0.87 ± 0.09 (GTV), 0.71 ± 0.09 (esophagus), 0.74 ± 0.09 (spinal cord), and 0.91 ± 0.05 (heart), respectively. Our proposed WCEM proved to be both practical and effective. The results clearly indicated that the grayscale registration method, when applied to the ipsilateral structure, achieved the highest CRF score. The average CRF scores, excellent rates, good rate and qualification rates were 58 ± 26, 40%, 75%, and 85%, respectively. CONCLUSIONS: This study successfully developed a clinically relevant weighted evaluation model for CBCT-guided lung cancer radiotherapy. Validation confirmed the grayscale method's optimal performance in ipsilateral structure registration.

Prospective evaluation of patient-reported outcomes of invisible ink tattoos for the delivery of external beam radiation therapy: the PREFER trial.

Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.

Intra-fractional lung tumor motion monitoring using arbitrary gantry angles during radiotherapy treatment.

Intensity-based 2D/3D registration using kilo-voltage (kV) and mega-voltage (MV) on-board imaging is a promising approach for real-time tumor motion tracking. So far, the performance of the kV images as well as kV-MV image pairs for 2D/3D registration using only one gantry angle (in anterior-posterior (AP) direction) has been investigated on patient data. In stereotactic body radiation therapy (SBRT), however, various gantry angles are typically used. This study attempts to answer the question of whether automatic 2D/3D registration is possible using kV images as well as kV-MV image pairs for gantry angles other than the AP direction. We also investigated the effect of additional portal MV images paired with kV images to improve 2D/3D registration in extracting cranio-caudal (CC) and AP displacement at arbitrary gantry angles and different fractions. The kV and MV image sequences as well as 3D volume data from five patients suffering from non-small cell lung cancer undergoing SBRT were used. Diaphragm motion served as the reference signal. The CC and AP displacements resulting from the registration results were compared with the corresponding reference motion signal. Pearson correlation coefficients (R value) was used to calculate the similarity measure between reference signal and the extracted displacements resulting from the registration. Signals we found that using 2D/3D registration tumor motion in 5 degrees of freedom (DOF) with kV images and in 6 degrees of freedom with kV-MV image pairs can be extracted for most gantry angles in all patients. Furthermore, our results have shown that the use of kV-MV image pairs increases the overall chance of tumor visibility and therefore leads to more successful extraction of CC as well as AP displacements for almost all gantry angles in all patients. We observed an improvement in registration of at least 0.29% more gantry angle for all patients when we used kV-MV images compared to kV images alone. In addition, an improvement in the R-value was observed in up to 16 fractions in various patients.

Consideration of image guidance in patterns of failure analyses of intensity-modulated radiotherapy for head and neck cancer: a systematic review.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) is considered standard of care for head and neck squamous cell carcinoma (HNSCC). Improved conformity of IMRT and smaller margins, however, have led to concerns of increased rates of marginal failures. We hypothesize that while patterns of failure (PoF) after IMRT for HNSCC have been published before, the quality of patient positioning and image guided radiotherapy (IGRT) have rarely been taken into account, and their importance remains unclear. This work provides a systematic review of the consideration of IGRT in PoF studies after IMRT for HNSCC. MATERIALS AND METHODS: A systematic literature search according to PRISMA guidelines was performed on PubMed for HNSCC, IMRT and PoF terms and conference abstracts from ESTRO and ASTRO 2020 and 2021 were screened. Studies were included if they related PoF of HNSCC after IMRT to the treated volumes. Data on patient and treatment characteristics, IGRT, treatment adaptation, PoF and correlation of PoF to IGRT was extracted, categorized and analyzed. RESULTS: One-hundred ten studies were included. The majority (70) did not report any information on IGRT. The remainder reported daily IGRT (18), daily on day 1-3 or 1-5, then weekly (7), at least weekly (12), or other schemes (3). Immobilization was performed with masks (78), non-invasive frames (4), or not reported (28). The most common PoF classification was "in-field/marginal/out-of-field", reported by 76 studies. Only one study correlated PoF in nasopharyngeal cancer patients to IGRT. CONCLUSION: The impact of IGRT on PoF in HNSCC is severely underreported in existing literature. Only one study correlated PoF to IGRT measures and setup uncertainty. Further, most PoF studies relied on outdated terminology ("in/out-of-field"). A clearly defined and up-to-date PoF terminology is necessary to evaluate PoFs properly, as is systematic and preferably prospective data generation. PoF studies should consistently and comprehensively consider and report on IGRT.

Surface guided radiotherapy practice in paediatric oncology: a survey on behalf of the SIOPE Radiation Oncology Working Group.

INTRODUCTION: Surface guided radiotherapy (SGRT) is increasingly being implemented to track patient's surface movement and position during radiation therapy. However, limited information is available on the SGRT use in paediatrics. The aim of this double survey was to map SIOPE (European Society for Paediatric Oncology)-affiliated centres using SGRT and to gain information on potential indications, observed, or expected benefits. METHODS: A double online survey was distributed to 246 SIOPE-affiliated radiotherapy (RT) centres. Multiple choices, yes/no, and open answers were included. The first survey (41 questions) was active from February to March 2021. A shortened version (13 questions) was repeated in March 2023 to detect trends in SGRT use within the same community. RESULTS: Respectively, 76/142 (54%) and 28/142 (20%) responding centres used and planned to use SGRT clinically, including 4/34 (12%) new centres since 2021. Among the SGRT users, 33/76 (43%) already applied this technology to paediatric treatments. The main benefits of improved patient comfort, better monitoring of intrafraction motion, and more accurate initial patient set-up expected by future users did not differ from current SGRT-users (P = .893). Among non-SGRT users, the main hurdles to implement SGRT were costs and time for installation. In paediatrics, SGRT is applied to all anatomical sites. CONCLUSION: This work provides information on the practice of SGRT in paediatrics across SIOPE-affiliated RT centres which can serve as a basis for departments when considering the purchase of SGRT systems. ADVANCES IN KNOWLEDGE: Since little information is available in the literature on the use of SGRT in paediatrics, the results of this double survey can serve as a basis for departments treating children when considering the purchase of an SGRT system.

Deep learning-based target tracking with X-ray images for radiotherapy: a narrative review.

Background and Objective: As one of the main treatment modalities, radiotherapy (RT) (also known as radiation therapy) plays an increasingly important role in the treatment of cancer. RT could benefit greatly from the accurate localization of the gross tumor volume and circumambient organs at risk (OARs). Modern linear accelerators (LINACs) are typically equipped with either gantry-mounted or room-mounted X-ray imaging systems, which provide possibilities for marker-less tracking with two-dimensional (2D) kV X-ray images. However, due to organ overlapping and poor soft tissue contrast, it is challenging to track the target directly and precisely with 2D kV X-ray images. With the flourishing development of deep learning in the field of image processing, it is possible to achieve real-time marker-less tracking of targets with 2D kV X-ray images in RT using advanced deep-learning frameworks. This article sought to review the current development of deep learning-based target tracking with 2D kV X-ray images and discuss the existing limitations and potential solutions. Finally, it also discusses some common challenges and potential future developments. Methods: Manual searches of the Web of Science, and PubMed, and Google Scholar were carried out to retrieve English-language articles. The keywords used in the searches included "radiotherapy, radiation therapy, motion tracking, target tracking, motion estimation, motion monitoring, X-ray images, digitally reconstructed radiographs, deep learning, convolutional neural network, and deep neural network". Only articles that met the predetermined eligibility criteria were included in the review. Ultimately, 23 articles published between March 2019 and December 2023 were included in the review. Key Content and Findings: In this article, we narratively reviewed deep learning-based target tracking with 2D kV X-ray images in RT. The existing limitations, common challenges, possible solutions, and future directions of deep learning-based target tracking were also discussed. The use of deep learning-based methods has been shown to be feasible in marker-less target tracking and real-time motion management. However, it is still quite challenging to directly locate tumor and OARs in real-time with 2D kV X-ray images, and more technical and clinical efforts are needed. Conclusions: Deep learning-based target tracking with 2D kV X-ray images is a promising method in motion management during RT. It has the potential to track the target in real time, recognize motion, reduce the extended margin, and better spare the normal tissue. However, it still has many issues that demand prompt attention, and further development before it can be put into clinical practice.

Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment.

Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

Carbon-Iodine Polydiacetylene Nanofibers for Image-Guided Radiotherapy and Tumor-Microenvironment-Enhanced Radiosensitization.

Radiotherapy is a mainstay treatment used in clinics for locoregional therapy, although it still represents a great challenge to improve the sensitivity and accuracy of radiotherapy for tumors. Here, we report the conjugated polymer, polydiiododiacetylene (PIDA), with an iodine content of 84 wt %, as a highly effective computed tomography (CT) contrast agent and tumor microenvironment-responsive radiosensitizer. PIDA exhibited several key properties that contribute to the improvement of precision radiotherapy. The integrated PIDA nanofibers confined within the tumor envelope demonstrated amplified CT intensity and prolonged retention, providing an accurate calculation of dose distribution and precise radiation delivery for CT image-guided radiotherapy. Therefore, our strategy pioneers PIDA nanofibers as a bridge to cleverly connect a fiducial marker to guide accurate radiotherapy and a radiosensitizer to improve tumor sensitivity, thereby minimizing potential damage to surrounding tissues and facilitating on-demand therapeutic intervention in tumors.

Predicting cervical cancer target motion using a multivariate regression model to enable patient selection for adaptive external beam radiotherapy.

Background and purpose: Interfraction motion during cervical cancer radiotherapy is substantial in some patients, minimal in others. Non-adaptive plans may miss the target and/or unnecessarily irradiate normal tissue. Adaptive radiotherapy leads to superior dose-volume metrics but is resource-intensive. The aim of this study was to predict target motion, enabling patient selection and efficient resource allocation. Materials and methods: Forty cervical cancer patients had CT with full-bladder (CT-FB) and empty-bladder (CT-EB) at planning, and daily cone-beam CTs (CBCTs). The low-risk clinical target volume (CTVLR) was contoured. Mean coverage of the daily CTVLR by the CT-FB CTVLR was calculated for each patient. Eighty-three investigated variables included measures of organ geometry, patient, tumour and treatment characteristics. Models were trained on 29 patients (171 fractions). The Two-CT multivariate model could use all available data. The Single-CT multivariate model excluded data from the CT-EB. A univariate model was trained using the distance moved by the uterine fundus tip between CTs, the only method of patient selection found in published cervix plan-of-the-day studies. Models were tested on 11 patients (68 fractions). Accuracy in predicting mean coverage was reported as mean absolute error (MAE), mean squared error (MSE) and R2. Results: The Two-CT model was based upon rectal volume, dice similarity coefficient between CT-FB and CT-EB CTVLR, and uterine thickness. The Single-CT model was based upon rectal volume, uterine thickness and tumour size. Both performed better than the univariate model in predicting mean coverage (MAE 7 %, 7 % and 8 %; MSE 82 %2, 65 %2, 110 %2; R2 0.2, 0.4, -0.1). Conclusion: Uterocervix motion is complex and multifactorial. We present two multivariate models which predicted motion with reasonable accuracy using pre-treatment information, and outperformed the only published method.

Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE).

BACKGROUND: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. MATERIALS AND METHODS: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type. RESULTS: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively. CONCLUSION: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy.

OBJECTIVE: This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. MATERIAL AND METHODS: TRUS was utilized during and after applicator insertion, with each needle's visibility documented through axial images at the high-risk clinical target volume's largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. RESULTS: Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ±â€¯0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and -0.1 ±â€¯1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. CONCLUSION: Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.