Weekly Image Guidance in Patients With Cervical Cancer Treated With Intensity-Modulated Radiation Therapy: Results of a Large Cohort Study.

BACKGROUND: Image guidance is recommended for patients undergoing intensity-modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long-term outcomes in a large cohort of patients. METHODS: The study enrolled patients with Stage IB-IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed. RESULTS: The median follow-up periods were 63.4 months. The incidence rates of loco-regional and distant failure were 9.9% and 13.6%. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5-year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5-year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para-aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty-six (4.0%) patients experienced late Grade 3/4 chronic toxicities. CONCLUSIONS: IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources.

Intensity-modulated proton radiotherapy spares musculoskeletal structures in regional nodal irradiation for breast cancer: a dosimetric comparison.

BACKGROUND AND PURPOSE: Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality. PATIENTS/MATERIAL AND METHODS: Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared. RESULTS AND INTERPRETATION: Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

Effect of replanning boost radiotherapy plan in locally advanced unresectable middle to lower thoracic esophageal cancer.

Thoracic bulky esophageal cancer shrinks during radiotherapy, changing the location and shape of the surrounding heart and lungs. The current study aimed to explore how replanning by volumetric-modulated arc radiotherapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) influences the target coverage and dose to organs at risk in locally advanced unresectable middle to lower thoracic esophageal cancer. We retrospectively collected CT simulation images of initial and boost radiotherapy plans for locally advanced unresectable thoracic esophageal cancer in 17 consecutive patients. First, we created boost plans of 20 Gy using 3DCRT and VMAT on the initially acquired CT images. Second, we replicated the process on CT images acquired after 20-40 Gy of radiotherapy. We then compared non-replanned boost radiotherapy plans with replanned boost plans. Replanned radiotherapy delivered more conformal doses to the target and reduced heart and lung doses. VMAT reduced more irradiated mean doses to the heart than 3DCRT in the case of replanning (1.7 and 1.1 Gy, p < 0.001). Replanning to accommodate tumor shrinkage during radiotherapy effectively lowers the irradiated doses to the heart and lungs in patients with locally advanced unresectable middle to lower thoracic esophageal cancer, especially those treated with VMAT.

Modeling of artificial intelligence-based respiratory motion prediction in MRI-guided radiotherapy: a review.

The advancement of precision radiotherapy techniques, such as volumetric modulated arc therapy (VMAT), stereotactic body radiotherapy (SBRT), and particle therapy, highlights the importance of radiotherapy in the treatment of cancer, while also posing challenges for respiratory motion management in thoracic and abdominal tumors. MRI-guided radiotherapy (MRIgRT) stands out as state-of-art real-time respiratory motion management approach owing to the non-ionizing radiation nature and superior soft-tissue contrast characteristic of MR imaging. In clinical practice, MR imaging often operates at a frequency of 4 Hz, resulting in approximately a 300 ms system latency of MRIgRT. This system latency decreases the accuracy of respiratory motion management in MRIgRT. Artificial intelligence (AI)-based respiratory motion prediction has recently emerged as a promising solution to address the system latency issues in MRIgRT, particularly for advanced contour prediction and volumetric prediction. However, implementing AI-based respiratory motion prediction faces several challenges including the collection of training datasets, the selection of prediction methods, and the formulation of complex contour and volumetric prediction problems. This review presents modeling approaches of AI-based respiratory motion prediction in MRIgRT, and provides recommendations for achieving consistent and generalizable results in this field.

Dosimetric comparison of gamma knife and linear accelerator (VMAT and IMRT) plans of SBRT of Lung tumours.

This study evaluates dosimetric differences in Stereotactic Body Radiation Therapy (SBRT) for lung tumors using plans of Gamma Knife, and Volumetric Modulated Arc Therapy (VMAT), Intensity-Modulated Radiation Therapy (IMRT) plans based on Linear Accelerator, aiming to inform the reader of appropriate treatment strategy selection. Ten patients with 23 lung tumor lesions treated with SBRT at Zhongshan Hospital of Dalian University were analyzed. Plans of Gamma Knife, and VMAT, IMRT plans based on Linear Accelerator were created for each lesion, totaling 18 plans per type. Lesions were treated with 30-50 Gy in 5-10 fractions. Dosimetric parameters, including gradient index (GI), heterogeneity index (HI), conformity index (CI), and doses to the plan target volumes (PTVs), the gross tumor volumes (GTVs) and organs at risk (OARs) were compared. Plans of Gamma Knife showed superior HI and GI, higher PTV and GTV doses, and reduced doses to the ipsilateral and contralateral lungs, esophagus, spinal cord, and heart compared to VMAT and IMRT plans (p < 0.05). However, Plans of Gamma Knife required longer delivery times. When comparing VMAT and IMRT plans, VMAT plans had shorter delivery times than IMRT plans, but required more monitor units (MUs). Additionally, IMRT plans delivered a lower mean dose to the ipsilateral lung compared to VMAT plans. Gamma Knife SBRT plans achieves steeper dose falloff and minimizes radiation to normal lung tissue compared to VMAT and IMRT plans, but with longer delivery times. VMAT and IMRT plans displayed similar dose distributions for lung SBRT.

Quality of life in disease-free survived patients with early-stage extranodal nasal-type NK/T-cell lymphoma after definitive intensity-modulated radiotherapy: a cross-sectional study of 310 cases.

PURPOSE: Radiotherapy is a critical treatment for early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTL) and has yielded favorable survival outcomes. However, their postradiotherapy quality of life (QOL) has not been investigated. Here, we conducted a cross-sectional study to assess the QOL of ENKTL patients with disease-free survival after definitive radiotherapy and to identify factors associated with QOL and treatment optimization. METHODS: This cross-sectional study included 310 patients with stage I-II ENKTL of the upper aerodigestive tract (UADT) who had received simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) with a consistent design and achieved disease-free survival. The median postradiotherapy time was 47.2 months (range, 3.1-115.7). The EORTC QLQ-H&N35 questionnaire was used to assess symptom-related QOL, and nine additional items were added to incorporate nasal, optical, and aural-related symptoms. The scores indicate the severity of the symptoms. RESULTS: The most common postradiotherapy symptoms among patients with ENKTL were nose problems (49.7%), dry mouth (44.8%), tooth problems (41.3%), sensory problems (32.6%), and less sexuality (25.8%). Tooth problems had the highest average score of 18.6, which is still acceptable. The severity of these symptoms decreased over time and reached a plateau in the second year after radiotherapy. Multivariable regression analysis showed that whole-neck irradiation was an independent predictive factor for xerostomia (P = 0.013, OR = 1.114), while age > 60 years was a predictive factor for lower sexuality (P < 0.001, OR = 1.32). CONCLUSION: The QOL of patients with early-stage ENKTL after radiotherapy was favorable, and most symptoms improved over time. Radiotherapy was correlated with specific symptoms, which may suggest a direction for further improvement in SIB-IMRT.

Impact of contrast-enhanced CT in the dosimetry of SBRT for liver metastases treated with MR-Linac.

BACKGROUND: To investigate the impact of using contrast-enhanced computed tomography (CHCT) in the dosimetry of stereotactic body radiation therapy (SBRT) for liver metastases treated with MR-Linac. METHODS: A retrospective study was conducted on 21 liver cancer patients treated with SBRT (50 Gy in 5 fractions) using a 1.5 Tesla Unity MR-Linac. The clinical treatment plans optimised on plain computed tomography (pCT) were used as reference. The electronic density (ED) of regions of interest (ROIs) including the liver, duodenum, esophagus, spinal cord, heart, ribs, and lungs, from pCT and CHCT, was analysed. The average ED of each ROI from CHCT was used to generate synthetic CT (sCT) images by assigning the average ED value from the CHCT to the pCT. Clinical plans were recalculated on sCT images. Dosimetric comparisons between the original treatment plan (TPpCT) and the sCT plan (TPsCT) were performed using dose-volume histogram (DVH) parameters, and gamma analysis. RESULTS: Significant ED differences (p < 0.05) were observed in the liver, great vessels, heart, lungs, and spinal cord between CHCT and pCT, with the lungs showing the largest differences (average deviation of 11.73% and 12.15% for the left and right lung, respectively). The target volume covered by the prescribed dose (VDpre), and the dose received by 2% and 98% of the volume (D2%, and D98%, respectively) showed statistical differences (p < 0.05), while the gradient index (GI) and the conformity index (CI) did not. Average deviations in target volume dosimetric parameters were below 1.02%, with a maximum deviation of 5.57% for. For the organs at risk (OARs), significant differences (p < 0.05) were observed for D0.35cc and D1.2cc of the spinal cord, D10cc for the stomach, D0.5cc for the heart, and D30% for the liver-GTV, with mean deviations lower than 1.83% for all the above OARs. Gamma analysis using 2%-2 mm criteria yielded a median value of 95.64% (range 82.22-99.65%) for the target volume and 99.40% (range 58-100%) for the OARs. CONCLUSION: The findings suggest that the use of CHCT in the SBRT workflow for liver metastases may result in minor target volume overdosage, indicating its potential for adoption in clinical settings. However, its use should be further explored in a broader context and tied to personalized treatment approaches.

Outcomes with optimal treatment in geriatric head and neck cancers - Tertiary cancer centre experience.

AIM: Older patients with locally advanced head and neck cancers (LA-HNC) are under-represented in clinical trials and denied standard treatment with concurrent chemo-radiation. Most are treated with radiotherapy (RT) alone. However, with the use of Intensity Modulated Radiation Therapy (IMRT) and good supportive care, even this cohort of patients can be considered for chemo-radiation. METHODS AND MATERIALS: 69 patients with age >65 years with LA-HNC treated between April 2015 and December 2019 in our Institute were prospectively evaluated for treatment compliance and outcomes. All patients were planned to receive 70 Gy in 33-35 fractions with IMRT and weekly Cisplatin at a dose of 40 mg/m2 (or Carboplatin-AUC-2). Loco-regional control (LRC), Overall survival (OS), and prognostic factors were evaluated. RESULTS: Median age at presentation was 67 years (65-81). 54 were male. 64% had Karnofsky Performance Status of >90. 42% had Oropharyngeal Primary. 17% had co-morbidities, 66% had T3 disease, 77% had Node positive disease, and 54% had Stage III disease. All patients completed 70 Gy and 81% patients received at least 5 (>200 mg/m2) chemotherapy cycles. Acute grade-3 toxicity was seen in 20% of patients and 64% had complete response. With a median follow up of 23.6 months (3-71), OS was 53.5%. Estimated 2-year LRC was 60%; estimated 2- and 5-year OS was 53.5% and 34.3%, respectively. On univariate analysis, age <70 years, Cisplatin use, limited nodal disease, Stage III, and complete response to treatment showed good OS (p < 0.05). CONCLUSION: Definitive chemo-IMRT approach in older patients with LA-HNC is well tolerated with good clinical outcomes. Hence, older age should not be a barrier for standard treatment.

Effect of bilateral superficial parotid gland sparing IMRT on xerostomia and QOL: A prospective study.

BACKGROUND: Superficial lobe constitutes 80% of the parotid and is situated lateral to mandible and can be better spared during intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC). This study aimed to see the impact of bilateral superficial parotid gland (PG) sparing IMRT on xerostomia and quality of life (QOL) in patients with HNC receiving radiation. STUDY DESIGN: Prospective, questionnaire-based study. MATERIALS AND METHODS: Thirty-four patients with histopathologically proven non-nasopharyngeal non-oral cavity HNC were included in this study. IMRT technique was used and a constraint of 24 Gy was given to combined superficial PG. Physician- and patient-rated xerostomia and QOL scores were recorded at baseline and two weeks, three months, and six months post-radiation therapy (RT). The combined superficial PG dose correlated with xerostomia and QOL scores. RESULTS: The combined superficial PG and combined whole PG mean dose was 18.71 Gy and 30 Gy, respectively, and the difference was statistically significant (P-< 0.001). At two weeks, three months, and six months post-RT, the odds of xerostomia scores were 0.11, 0.071, 0.042, respectively for a median dose of <18 Gy compared to >18 Gy and was statistically significant P=(0.001). CONCLUSION: Bilateral superficial PG sparing IMRT is beneficial in reducing xerostomia and translates to a better QOL.

Can dysphagia aspiration related structures (DARS) be spared in patients with oropharyngeal cancers? Dosimetric evaluation in a prospective study of DARS optimized intensity modulated radiation therapy.

PURPOSE: To evaluate the feasibility of sparing the dysphagia-aspiration-related structures (DARS) in various head and neck cancer sites treated with definitive DARS-optimized intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: Target volumes, organs at risk, and in addition, individual DARS were delineated, including the superior, middle, and inferior pharyngeal constrictor muscles, supraglottic and glottic larynx, the base of the tongue, esophageal inlet muscles and cervical esophagus in 35 patients with head and neck squamous cell carcinoma. Volume-based dose constraints were applied to the DARS outside the planning target volume (PTV). An IMRT plan was then generated to limit doses to DARS without compromising PTV dose coverage. RESULTS: Twelve (34.3%) patients had an oropharyngeal primary (OPX), 18 (51.4%) had a laryngeal, and 5 (14.3%) patients had hypopharyngeal primary. The mean dose to the DARS was 47.93 Gy for the entire group, while it was 54.6 Gy in oropharyngeal primaries and 44.4 Gy in laryngopharyngeal primaries. DARS mean dose of ≤45 Gy could be achieved in a significantly lesser number of patients with oropharyngeal primaries (P < 0.02). Similarly, DARS mean dose was 42.25 Gy in patients with N0 disease, 49.6 Gy with ipsilateral involved nodes, and 55 Gy with bilateral disease. Sparing of DARS was feasible when the volume of PTV was ≤150 cc (P < 0.025). CONCLUSION: Sparing of DARS structures appears to be challenging in patients with oropharyngeal cancers without compromising the dose to the PTVs while it is feasible in laryngopharyngeal cancers. DARS sparing is feasible when the PTV volume is < 150 cc and in patients with negative or unilateral nodal disease.

Evaluation of gross target volumes in CECT vs MRI in head and neck cancer and its implication on concordance indices and dose-volume parameters of IMRT treatment plan.

BACKGROUND: Although radiotherapy treatment planning (RTP) for head and neck cancers (HNCs) is based on contrast enhanced computed tomography (CECT), soft tissue contrasts are better evident on magnetic resonance imaging (MRI). We therefore evaluated dose-volume histogram (DVH) parameters along with concordance index (ConI), conformity index (CI), and homogeneity index (HI) of planning target volume (PTV) of GTV delineated on CECT vs MRI in HNCs enrolled for intensity modulated radiotherapy (IMRT). METHODOLOGY: Forty consecutive HNCs were enrolled in this study. All underwent CECT and MRI simulations with immobilization devices. GTVp and GTVn were delineated independently on CECT and MRI images. Corresponding MRI volumes were then copied to CECT. IMRT plans were generated on the CECT incorporating PTV margins. DVH parameters of PTVpn for both CECT and MRI were compared. In addition, mean (±SD) percentage difference of GTVp, GTVn, GTVpn, ConI, CI, and HI were evaluated using paired t-test. RESULTS: The GTVp (P = 0.005), GTVn (P = 0.009), and GTVpn (P < 0.001) delineated on MRI were found to be significantly larger than GTV delineated on CECT. In eight patients, GTV outlined on CECT were larger than MRI. Significant mean differences in CECT vs MRI of CI (P < 0.001), HI (P < 0.001), ConI (P < 0.001), and DVH parameters (D2, D95, D98, V95, and V100 all P < 0.001; D50: P = 0.009) were noted. CONCLUSION: The GTVs and corresponding PTVs were significantly larger on MRI compared to CECT. This resulted in significant differences in DVH parameters, CI, ConI, and HI. This could be improved by co-registered MRI-CECT volumes during routine IMRT treatment planning for HNCs.

Comparison of long-term quality of life and their predictors in survivors between paediatric and adult nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL. METHODS: We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared. RESULTS: The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), role function (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), social function (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038), insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001), but poorer cognitive function (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than the adult group. Pretreatment clinical factors, including T stage, N stage, and pre-treatment EBV (Epstein-Barr Virus) DNA, showed a strong association with QoL. However, the factors that affected the QoL outcomes differed between the two groups. In survivors of paediatric cancer, global health status/QoL was strongly correlated with T stage (P < 0.001) and clinical stage (P = 0.018), whereas it was strongly correlated with pre-treatment EBV DNA (P = 0.008) in adults. CONCLUSION: Paediatric survivors of NPC have a significantly better QoL than adult NPC survivors. Moreover, pre-treatment T stage, N stage, and EBV DNA significantly influenced the overall health status of the survivors. These results highlight the need to tailor care to both age groups to promote better long-term health outcomes.

A deep learning-based dose calculation method for volumetric modulated arc therapy.

BACKGROUND: Volumetric modulated arc therapy (VMAT) planning optimization involves iterative adjustment of numerous parameters, and hence requires repeatedly dose recalculation. In this study, we used the deep learning method to develop a fast and accurate dose calculation method for VMAT. METHODS: The classical 3D UNet was adopted and trained to learn the physics principle of dose calculation. The inputs included the projected fluence map (FM), computed tomography (CT) images, the radiological depth and the source-to-voxel distance (SVD). The projected FM was generated by projecting the accumulated FM between two consecutive control points (CPs) onto the patient's anatomy. The accumulated FM was calculated by simulating the movement of the multi-leaf collimator (MLC) from one CP to the next. The dose, calculated by the treatment planning system (TPS), was used as ground truth. 51 head and neck VMAT plans were used, with 43, 1 and 7 cases as training, validation, and testing datasets, respectively. Correspondingly, 7182, 180 and 1260 CP samples were included in the training, validation, and testing datasets. RESULTS: This presented method was evaluated by comparing the derived dose distribution to the TPS calculated dose distribution. The dose profiles coincided for both the single CP and the entire plan (summation of all CPs). But the network derived dose was smoother than the TPS calculated dose. Gamma analysis was performed between the network derived dose and the TPS calculated dose. The average gamma pass rate was 96.56%, 98.75%, 98.03% and 99.30% under the criteria of 2% (tolerance) -2 mm (distance to agreement, DTA). 2%-3 mm, 3%-2 mm and 3%-3 mm. No significant difference was observed on the critical indices including the max, mean dose, and the relative volume covered by the 2000 cGy, 4000 cGy and the prescription dose. For one CP, the average computational time of the network and TPS was 0.09s and 0.53s. And for one patient, the average time was 16.51s and 95.60s. CONCLUSION: The dose distribution derived by the network showed good agreement with the TPS calculated dose distribution. The computational time was reduced to approximate one-sixth of its original duration. Therefore the presented deep learning-based dose calculation method has the potential to be used for planning optimization.

Minimizing human interference in an online fully automated daily adaptive radiotherapy workflow for bladder cancer.

PURPOSE: The aim was to study the potential for an online fully automated daily adaptive radiotherapy (RT) workflow for bladder cancer, employing a focal boost and fiducial markers. The study focused on comparing the geometric and dosimetric aspects between the simulated automated online adaptive RT (oART) workflow and the clinically performed workflow. METHODS: Seventeen patients with muscle-invasive bladder cancer were treated with daily Cone Beam CT (CBCT)-guided oART. The bladder and pelvic lymph nodes (CTVelective) received a total dose of 40 Gy in 20 fractions and the tumor bed received an additional simultaneously integrated boost (SIB) of 15 Gy (CTVboost). During the online sessions a CBCT was acquired and used as input for the AI-network to automatically delineate the bladder and rectum, i.e. influencers. These influencers were employed to guide the algorithm utilized in the delineation process of the target. Manual adjustments to the generated contours are common during this clinical workflow prior to plan reoptimization and RT delivery. To study the potential for an online fully automated workflow, the oART workflow was repeated in a simulation environment without manual adjustments. A comparison was made between the clinical and automatic contours and between the treatment plans optimized on these clinical (Dclin) and automatic contours (Dauto). RESULTS: The bladder and rectum delineated by the AI-network differed from the clinical contours with a median Dice Similarity Coefficient of 0.99 and 0.92, a Mean Distance to Agreement of 1.9 mm and 1.3 mm and a relative volume of 100% and 95%, respectively. For the CTVboost these differences were larger, namely 0.71, 7 mm and 78%. For the CTVboost the median target coverage was 0.42% lower for Dauto compared to Dclin. For CTVelective this difference was 0.03%. The target coverage of Dauto met the clinical requirement of the CTV-coverage in 65% of the sessions for CTVboost and 95% of the sessions for the CTVelective. CONCLUSIONS: While an online fully automated daily adaptive RT workflow shows promise for bladder treatment, its complexity becomes apparent when incorporating a focal boost, necessitating manual checks to prevent potential underdosage of the target.

Very pronounced bowel sparing during radiation therapy for anal carcinoma using a natural spacer (Myoma) - a case report.

BACKGROUND: Using dose-painted intensity-modulated radiation therapy, specific dose volume constraints or implantation of tissue expanders prior to radiotherapy are validated options for reducing radiation dose on the bowel and therefore minimizing acute gastrointestinal toxicity during chemoradiation for anorectal malignancies. We describe the rare case of a female patient with a locally advanced anal carcinoma where a large myomatous uterus served as a natural spacer to protect the bowel during radiation therapy. CASE PRESENTATION: Initially the patient presented with anal pain, proctoscopy followed by an excisional biopsy confirmed the diagnosis of a squamous cell carcinoma of the anus. Imaging examination showed a locally advanced tumor and in addition a large uterus with typical leiomyomas up to 11.5 cm in diameter. The patient underwent chemoradiation; because of the large leiomyomas there was almost no dose burden for the small intestine and therefore practically no gastrointestinal toxicity. CONCLUSION: As we know, this report describes the situation that a large myomatous uterus served as a natural spacer during radiation therapy in a way that is unique to date.

Early recurrence as a pivotal event in nasopharyngeal carcinoma: identifying predictors and key molecular signals for survivors.

PURPOSE: The duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors. METHODS: This investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER. RESULTS: Our results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response. CONCLUSIONS: Our comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression.

The Dose Difference of Dominant Intraprostatic Lesions (DILs) Defined by Magnetic Resonance-Guided and arc-based Intensity Modulated Radiation Therapy (IMRT), and the Association between Dose Difference and Recurrent Prostate Cancer.

BACKGROUND: There is growing evidence that local recurrence after radiotherapy often occurs within the dominant intraprostatic lesions (DILs) in prostate cancer. This study aimed to evaluate the dose difference between DILs defined by Magnetic Resonance-guided and arc-based Intensity Modulated Radiation Therapy (IMRT) and to assess the association between the dose difference and biochemical recurrence-free survival. MATERIALS AND METHODS: Between 2015 and 2019, 48 prostate cancer patients with DILs visible from multiparametric Magnetic Resonance Imaging (mpMRI) underwent arc-based IMRT with 70 Gy (2.5 Gy each fraction) to the prostate gland. Pretreatment mpMRI DILs contoured the prostate gland retrospectively. RESULTS: Biochemical recurrence was 8.3%. There was a significant difference between the median dose of DILs from MRI-guided imaging, 69.22 Gy, and the median dose of the whole prostate from arc-based IMRT which was 67.09 Gy (p < 0.001*). The Kaplan-Meier survival curve compared by log-rank test showed an escalation dose of at least 2 Gy tends to improve biochemical recurrence-free survival. However, this tendency did not reach statistical significance (p = 0.2). CONCLUSIONS: The dose distribution within DILs defined by mpMRI is significantly higher than the whole prostate dose from arc-based IMRT. Escalation doses in DILs tend to improve biochemical recurrence-free survival, further validation in larger patient cohorts with extended follow-up is warranted.

Impact of Reference Selection on Gamma Analysis in Patient-Specific Quality Assurance for Monte Carlo-Based Treatment Planning Systems.

OBJECTIVE: Our study aimed to establish a standardized methodology for selecting "reference" and "evaluated" distributions in gamma analysis for Monte Carlo (MC) based intensity modulated treatment plans. Evaluation of importance of reference selection in MC based and non MC based treatment planning systems were analysed using a study classification. METHODS: Three categories were utilized to analyzed gamma passing rates across using different treatment planning systems (TPS) and detectors for thirty five patients. Category 1 utilized MC-based Monaco TPS plans and a 2 dimensional(2D) I'mRTMatriXX detector. Category 2 employed non-MC-based Eclipse TPS plans, assessed with a 2D I'mRTMatriXX detector. In Category 3, MC-based Monaco TPS plans were validated using a Dolphin detector. All plans were subjected to analysis using gamma criteria, which considered a dose difference of 3% and a distance to agreement of 3mm. Additionally, another set of gamma criteria was employed, with a dose difference of 3% and a distance to agreement of 2mm. An introduced Asymmetric factors in both 2D and 3D analysis will quantify the asymmetric nature of gamma based on the choice of "reference" distribution. RESULT: For 2D Gamma analysis, MC-based Monaco TPS and I'mRTMatriXX showed a consistent positive Zk2D trend for all patients, with significant p-values below 0.01 for both gamma passing criteria. In contrast, non-MC based Eclipse TPS exhibited varied Zk2D results, with non-significant p-values. In 3D Gamma analysis, all patients exhibited positive Zk3D values with significant p-values below 0.01 when "references" were swapped. The Pearson correlation between asymmetricity and isodose volumes was notably high at 0.99 for both gamma criteria. CONCLUSION: Our study highlights the imperative of using MC-based TPS as the definitive "reference" in gamma analysis for patient specific quality assurance of intensity modulated radiation therapy, emphasizing that variations can mislead results, especially given gamma analysis's sensitivity to MC calculation noise.

Dose escalation in radical radio(chemo)therapy for cervical and upper thoracic esophageal cancer with 3DCRT/IMRT (ChC&UES): a multicenter retrospective study.

BACKGROUND: Cervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose. METHOD: We retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50-55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55-63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS). RESULTS: The median OS was 33.0 months (95% CI: 29.401-36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05). CONCLUSION: HD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn't improve survival but enhances ORR.

Preliminary study of feasibility of surface-guided radiotherapy with concurrent tumor treating fields for glioblastoma: region of interest.

OBJECTIVE: To evaluate the impact of the residual setup errors from differently shaped region of interest (ROI) and investigate if surface-guided setup can be used in radiotherapy with concurrent tumor treating fields (TTFields) for glioblastoma. METHODS: Fifteen patients undergone glioblastoma radiotherapy with concurrent TTFields were involved. Firstly, four shapes of region of interest (ROI) (strip-shaped, T-shaped, ⊥ -shaped and cross-shaped) with medium size relative to the whole face were defined dedicate for patients wearing TTFields transducer arrays. Then, ROI-shape-dependent residual setup errors in six degrees were evaluated using an anthropomorphic head and neck phantom taking CBCT data as reference. Finally, the four types of residual setup errors were converted into corresponding dosimetry deviations (including the target coverage and the organ at risk sparing) of the fifteen radiotherapy plans using a feasible and robust geometric-transform-based method. RESULTS: The algebraic sum of the average residual setup errors in six degrees (mm in translational directions and ° in rotational directions) of the four types were 6.9, 1.1, 4.1 and 3.5 respectively. In terms of the ROI-shape-dependent dosimetry deviations, the D98% of PTV dropped off by (3.4 ± 2.0)% (p < 0.05), (0.3 ± 0.5)% (p < 0.05), (0.9 ± 0.9)% (p < 0.05) and (1.1 ± 0.8)% (p < 0.05). The D98% of CTV dropped off by (0.5 ± 0.6)% (p < 0.05) for the strip-shaped ROI while remained unchanged for others. CONCLUSION: Surface-guided setup is feasible in radiotherapy with concurrent TTFields and a medium-sized T-shaped ROI is appropriate for the surface-based guidance.