Image-guided Intensity-modulated Radiotherapy Research Articles

Longitudinal Costs of Image-Guided Intensity-Modulated Radiation Therapy Versus Three-Dimensional Conformal Radiation: Lessons From Phase III PARCER Trial for Shaping Resource-Stratified Guidelines in Low- and Middle-Income Countries.

The PARCER trial provided level I evidence for image-guided intensity-modulated radiation therapy (IG-IMRT) in patients with cervical cancer. Further information regarding long-term financial impact is imperative for adoption into the National Cancer Grid of India cervical cancer resource-stratified guidelines. Patient data from the PARCER trial were analyzed to evaluate the cost implications of transitioning to IG-IMRT. Lacking differences in outcomes between the three-dimensional conformal radiation (3D-CRT) and IG-IMRT, differences in treatment costs, adverse event incidence, and toxicity management costs were examined. The overall financial impact was estimated by adding the treatment costs, toxicity management, and wage loss. This was extrapolated nationally to determine if a transition to IG-IMRT would be feasible for the Indian health care system. Of the 300 patients in the PARCER trial, 93 faced grades ≥2 adverse events (3D-CRT = 59, IG-IMRT = 34). Patients in the 3D-CRT and IG-IMRT arms spent an average of 2.39 years and 1.96 years in toxicity, respectively. The average toxicity management and the yearly financial impact per patient were, respectively, 1.50 and 1.44 times higher for 3D-CRT patients compared with IG-IMRT patients. Extrapolation to the national level showed that treatment with 3D-CRT led to a 2.88 times higher cost ratio when compared with treatment with IG-IMRT. Although the initial costs of IG-IMRT are high, on the basis of longitudinal data, it is financially inefficient to treat with 3D-CRT. Resource-stratified guidelines should include longitudinal health intervention costs rather than solely initial costs for policy decisions to implement advanced radiation technology.

Simulation and pre-planning omitted radiotherapy (SPORT): a feasibility study for prostate cancer

This study explored the feasibility of on-couch intensity modulated radiotherapy (IMRT) planning for prostate cancer (PCa) on a cone-beam CT (CBCT)-based online adaptive RT platform without an individualized pre-treatment plan and contours. Ten patients with PCa previously treated with image-guided IMRT (60 Gy/20 fractions) were selected. In contrast to the routine online adaptive RT workflow, a novel approach was employed in which the same preplan that was optimized on one reference patient was adapted to generate individual on-couch/initial plans for the other nine test patients using Ethos emulator. Simulation CTs of the test patients were used as simulated online CBCT (sCBCT) for emulation. Quality assessments were conducted on synthetic CTs (sCT). Dosimetric comparisons were performed between on-couch plans, on-couch plans recomputed on the sCBCT and individually optimized plans for test patients. The median value of mean absolute difference between sCT and sCBCT was 74.7 HU (range 69.5–91.5 HU). The average CTV/PTV coverage by prescription dose was 100.0%/94.7%, and normal tissue constraints were met for the nine test patients in on-couch plans on sCT. Recalculating on-couch plans on the sCBCT showed about 0.7% reduction of PTV coverage and a 0.6% increasing of hotspot, and the dose difference of the OARs was negligible (<0.5 Gy). Hence, initial IMRT plans for new patients can be generated by adapting a reference patient’s preplan with online contours, which had similar qualities to the conventional approach of individually optimized plan on the simulation CT. Further study is needed to identify selection criteria for patient anatomy most amenable to this workflow.

Small Bowel Dose Constraints in Radiation Therapy—Where Omics-Driven Biomarkers and Bioinformatics Can Take Us in the Future

Radiation-induced gastrointestinal (GI) dose constraints are still a matter of concern with the ongoing evolution of patient outcomes and treatment-related toxicity in the era of image-guided intensity-modulated radiation therapy (IMRT), stereotactic ablative radiotherapy (SABR), and novel systemic agents. Small bowel (SB) dose constraints in pelvic radiotherapy (RT) are a critical aspect of treatment planning, and prospective data to support them are scarce. Previous and current guidelines are based on retrospective data and experts’ opinions. Patient-related factors, including genetic, biological, and clinical features and systemic management, modulate toxicity. Omic and microbiome alterations between patients receiving RT to the SB may aid in the identification of patients at risk and real-time identification of acute and late toxicity. Actionable biomarkers may represent a pragmatic approach to translating findings into personalized treatment with biologically optimized dose escalation, given the mitigation of the understood risk. Biomarkers grounded in the genome, transcriptome, proteome, and microbiome should undergo analysis in trials that employ, R.T. Bioinformatic templates will be needed to help advance data collection, aggregation, and analysis, and eventually, decision making with respect to dose constraints in the modern RT era.

Clinical Implementation of “Plan of the Day” Strategy in Definitive Radiation Therapy of Cervical Cancer: Online Adaptation to Address the Challenge of Organ Filling Reproducibility

Background: Definitive pelvic intensity-modulated radiotherapy (IMRT) in cervical cancer is susceptible to geographic miss due to daily positional and volumetric variations in target and organs at risk. Hence, despite evidence of reduced acute and late treatment-related toxicities, implementation of image-guided IMRT (IG-IMRT) with a reasonable safety margin to encompass organ motion is challenging. Materials and Methods: In this prospective, non-randomized phase II study, patients with cervical cancer FIGO (2009) stage IB2-IIIB between the ages of 18 and 65 years were treated with definitive pelvic CT-RT with a pre-specified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily comprehensive adaptive IGRT, with a library of 3 IMRT (VMAT) plans with incremental expansions of CTV to PTV (Primary) margins (small 0.7 cm, adequate 1 cm and large 1.5 cm) and a backup motion robust 3DCRT plan; the appropriate plan is chosen based on pre-treatment CBCT (‘Plan of the Day’ approach). Results: Fifty patients with a median age of 49 years (IQR 45-56 years), received definitive RT (45-46Gy in 23-25 fractions to pelvis; with simultaneous integrated boost to gross nodes in 15 patients) with the said IGRT protocol. In the analysis of 1171 CBCT images (in 1184 treatment sessions), the mean planning CT and CBCT bladder volumes were 417 ccs and 373 ccs respectively. Significant inter-fractional variation in bladder volume was noted with a mean absolute dispersion of 29.5% with respect to planning CT; significant influential random factors were post-chemotherapy sessions (p=<0.001), pre-CBCT protocol duration (p= 0.001), grades of CINV (p=0.001). Significantly higher variation in bladder filling noted in patients with higher age (p=0.014) and larger planning CT bladder volume (p=<0.001). Time trend analysis of fraction-wise bladder volume revealed an absolute systemic reduction of 16.3% in bladder volume means from 1st to 5th week. Variation in rectal diameter was much less pronounced, with 19.2% mean dispersion, without any significant factors affecting it.While in 19% and 2% of sessions ‘Large’ IMRT PTV and ‘3DCRT’ were necessary to cover the primary target respectively, reduction in treated volume was possible in 43% of sessions with ‘Small’ PTV selection instead of standard ‘Adequate’ PTV (36% sessions). ‘Plan of the day’ selection had a moderate to strong correlation with non-absolute dispersion of bladder filling (Spearman's R= 0.4; p= 0.001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no radiation-induced local grade III toxicity. Conclusion: Inter-fractional variation in organ filling (especially bladder) is inevitable despite fixed pre-treatment protocol in definitive settings (intact cervix). Despite the logistical challenges; adaptive IGRT in form of ‘plan of the day’ based on incremental CTV-to-PTV margins is a relatively simple and feasible strategy to minimise geometric uncertainties in radical IG-IMRT of cervical cancer.

Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Long-Term Results From the PKUFH Randomized Phase 3 Trial

PURPOSEIn the randomized, single-center, PKUFH phase III trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the two cohorts at 4 years. In the current analysis, we provide 7-year outcomes. MATERIALS AND METHODSPatients with stage pT3-4, positive surgical margins, or prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image-guided intensity-modulated radiotherapy. The primary end point was bPFS. Secondary end points were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS), as estimated using the Kaplan–Meier method. RESULTSBetween September 2011 and November 2016, 144 patients were enrolled, with 73 and 71 in the 72 and 66 Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72 and 66 Gy cohorts (70.3% vs 61.2%; hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.41-1.29; P = 0.274). However, in patients with a higher Gleason score (GS 8-10), the 72 Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66 Gy cohort (66.5% vs 30.2%; HR = 0.37, 95%CI: 0.17-0.82; P = 0.012). In addition, in patients with multiple positive surgical margins (mSM+), the 72 Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR = 0.36, 95%CI: 0.13-0.99; P = 0.037). The 7-year DMFS (88.4% vs 84.9%; HR = 0.93, 95%CI: 0.39-2.23; P = 0.867), CSS (94.1% vs 95.5%; HR = 1.19, 95%CI: 0.42-3.39; P = 0.745), and OS (92.8% vs 94.1%; HR = 1.29, 95%CI: 0.51-3.24; P = 0.594) had no statistically difference between the 72 and 66 Gy cohorts. CONCLUSIONThe current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared to the 66 Gy regimen. However, patients with a higher GS (8-10) or mSM+ might benefit from the 72 Gy regimen, but this requires further prospective research.

Outcomes of dose-escalated IMRT and ADT in Octogenarians with prostate cancer.

We evaluated long-term outcomes for octogenarians with localised prostate cancer treated using dose-escalated image-guided intensity-modulated radiation therapy (IMRT) at our institution. The charts of octogenarians treated for localised prostate cancer were retrospectively reviewed. Overall survival (OS), prostate cancer-specific survival (PCaSS), toxicity rates and changes from baseline were collected. The median follow-up was 97 months. Of 107 eligible patients, 27.1% had intermediate-risk and 72.9% had high-risk localised prostate cancer. Median dose was 78Gy, and 97.2% received ADT. OS was 91.4% and 67.2% at 5 and 10 years. PCaSS was 98.0% and 88.7% at 5 and 10 years. In all, 39 (36.4%) of patients died, with the cause of death known in 30: in 26.7% of these patients, prostate cancer was the cause of death. Grade ≥ 2 late GI and GU toxicity was 0.9% and 24.3% respectively. In all, 11.2% and 22.4% of patients reported worsening of GI or GU function from baseline, and 13.1% and 21.5% reported improvement in GI and GU function compared to baseline. Selected octogenarian patients with localised prostate cancer appear to benefit from radiation therapy and ADT. Despite excellent long-term PCaSS, 26.7% of patients died of prostate cancer. Rates of GI and GU toxicity were acceptable, and deterioration of urinary and bowel function compared to baseline was just as common as improvement in function from baseline.

Boron Neutron Capture Therapy Followed by Image-Guided Intensity-Modulated Radiotherapy for Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

This trial investigated the efficacy and safety of salvage boron neutron capture therapy (BNCT) combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for recurrent head and neck cancer after prior radiotherapy (RT). BNCT was administered using an intravenous boronophenylalanine-fructose complex (500 mg/kg) in a single fraction; multifractionated IG-IMRT was administered 28 days after BNCT. For BNCT, the mucosa served as the dose-limiting organ. For IG-IMRT, the clinical target volume (CTV) and the planning target volume (PTV) were generated according to the post-BNCT gross tumor volume (GTV) with chosen margins. This trial enrolled 14 patients, and 12 patients received combined treatment. The median BNCT average dose for the GTV was 21.6 Gy-Eq, and the median IG-IMRT dose for the PTV was 46.8 Gy/26 fractions. After a median (range) follow-up period of 11.8 (3.6 to 53.2) months, five patients had a complete response and four had a partial response. One patient had grade 4 laryngeal edema; another patient had a grade 4 hemorrhage. Most tumor progression occurred within or adjacent to the CTV. The 1-year overall survival and local progression-free survival rates were 56% and 21%, respectively. Despite the high response rate (64%) of this trial, there was a high incidence of in-field and marginal failure with this approach. Future studies combining BNCT with modalities other than radiation may be tried.

Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image-guided intensity modulated radiation therapy in locally advanced rectal cancers.

155 Background: The paradigm of locally advanced (T3/4; T1-4N1-2) rectal cancers (LARC) requires an intensified treatment for better pathological outcomes. Treatment intensification may be done by radiation dose escalation of long course neoadjuvant chemoradiation therapy (NACRT) by image guided Intensity Modulated Radiation Therapy (IG-IMRT) to increase downstaging with potentially higher local control rates. We aimed to analyze the efficacy and safety of NACRT with dose escalated IG-IMRT in LARC. Methods: 20 patients of LARC were recruited in this prospective interventional phase-II study treated by IG-IMRT with 45 Gray/25 fractions to elective nodal volumes and concomitant boost of 55 Gray/25 fractions to gross primary and nodal disease with concurrent capecitabine (825 mg/m2 twice a day on radiation days). All were planned to undergo definitive surgery 6-8 weeks post completion of NACRT with Total mesorectal excision by Low anterior resection (LAR) or Abdominoperineal resection (APR) followed by 6-8 cycles of adjuvant chemotherapy. Post operative response assessment was assessed by Modified Ryan’s scheme for regression and by tumor downstaging. Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Of 20 patients, 18 underwent definitive surgery and received full course adjuvant chemotherapy (90%). Median follow up was 15.1 months. 2 patients refused surgery, had complete clinical response (cCR) on assessment and were on follow up. Tumor downstaging was achieved in 14 (77.7%) patients and nodal downstaging was achieved in 15/18 (83.3%) patients. In 4 patients (22.2%) pCR was achieved and overall complete response (OCR defined as pCR and nearCR, including 2 patients with cCR) in 10 patients (50%). 4 patients planned for APR underwent LAR achieving a sphincter preservation rate of 22%. Grade 3 toxicities were observed in 2 patients which resolved on first follow up. No Grade 4 acute toxicities were reported. No loco-regional relapses were found and all patients are disease free at the time of last follow up. Conclusions: Dose escalation with IG-IMRT offers higher rates of pCR and OCR with acceptable toxicity profile and excellent short term locoregional control. [Table: see text]

Survival effect of pre-RT PET-CT on cervical cancer: Image-guided intensity-modulated radiation therapy era.

No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). This is the first head-to-head propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving image-guided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT.

Combination of image-guided IMRT and IGBT in locally advanced carcinoma cervix: Prospective evaluation of toxicities and clinical outcomes from a tertiary cancer center in India.

We aimed to assess the toxicity profile and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with a combination of image-guided intensity-modulated radiation therapy (IG-IMRT) and image-guided brachytherapy (IGBT). 25 LACC patients were recruited in this single-arm prospective study. Whole pelvis IG-IMRT was delivered (45 Gy with simultaneously integrated nodal boost of 55 Gy in 25 fractions), with concurrent weekly cisplatin (40 mg/m2). Patients received IGBT of 7 Gy each in 4 fractions to high-risk clinical target volume (HR-CTV). First fraction was done under MRI, and subsequent fractions were performed under CT guidance. Primary endpoint was acute toxicity, and secondary endpoints were 2-year loco-regional control and late toxicity. The median age was 52 years, and FIGO 2018 stage distribution was IIA2, IIB, IIIB, and IIIC1 in 12%, 40%, 20%, and 28% patients, respectively. All patients received concurrent chemotherapy with median number of 5 cycles (range, 4-5 cycles). Grade 1 and 2 diarrhea, and grade 1 cystitis was reported in 4 (16%), 3 (12%), and 2 (8%) patients, respectively. Grade 1 and 2 anemia, and grade 1 and 2 dermatitis were observed in 3 (12%) and 2 (8%), and 3 (12%) and 3 (12%) patients, respectively. No patient reported grade 3-4 acute toxicity. At median follow-up of 29.5 months (range, 25-37 months), late grade 1 bladder toxicity was observed in 1 (4%) patient. Loco-regional control at 1 and 2 years were 96% and 92%, respectively. The combination of IG-IMRT and IGBT yielded excellent outcomes in terms of acute toxicity and loco-regional control.

Image-guided intensity-modulated radiotherapy in patients with FIGO IIIC1 cervical cancer: efficacy, toxicity and prognosis.

Background: To investigate the efficacy, toxicity and prognosis of image-guided intensity-modulated radiotherapy (IG-IMRT) in patients with FIGO IIIC1 cervical cancer. Methods: We retrospectively reviewed clinical records of patients with FIGO IIIC1 cervical cancer treated with definitive IG-IMRT in our institute from January 2008 to December 2017. A dose of 50.4Gy in 28 fractions was prescribed to at least 95% of PCTV, the positive pelvic lymph nodes received a dose of 56-61.6Gy in 28 fractions with simultaneous integrated boost (SIB). Weekly cone beam compute tomography (CBCT) and daily megavoltage CT (MVCT) was performed before treatment. Both 2D brachytherapy and 3D brachytherapy were allowed in our study. Weekly Cisplatin (30-40mg/m2) was the first line regimen for concurrent chemotherapy. Overall survival (OS), disease free survival (DFS), local control (LC) and local regional control (LRC) was calculated with Kaplan-Meier method. Cox proportional hazard model was used to perform univariate and multivariate analyses. Results: A total of 502 patients were enrolled in this study. The median follow-up duration was 42.1 months (range: 2.3-137.3 months). The 3-year and 5-year estimated OS, DFS, LC, LRC were 81.7% and 75.5%, 71.4% and 68.6%, 89.9% and 89.9%, 86.1% and 84.3%, respectively. The incidences of chronic grade 3 or greater gastrointestinal and genitourinary toxicities were 2.7 % and 0.8%, respectively. Pelvic lymph nodes recurrence occurred in 21 patients (4.2%). Advanced T stage was identified as adverse factor for OS and LC. More positive lymph nodes (≥2) were associated with worse OS, DFS and LRC. The cycles of concurrent chemotherapy significantly affected OS, DFS and LRC. Conclusion: For patients with FIGO IIIC1 cervical cancer, IG-IMRT was well tolerated with excellent survivals. T stage and number of positive lymph nodes significantly influenced the survivals indicating the heterogeneity of stage IIIC1 cervical cancer patients. Adequate cycles of chemotherapy (≥4 cycles) was of great value for this group of patients.

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer

BackgroundThis study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy. Materials and MethodsPatients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea). ResultsIn total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break. ConclusionStatistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Planning Margins Determined by Inter Fractional Errors for Patients with Hepatocarcinoma—A Real-World Practice

<h3>Purpose/Objective(s)</h3> With the progress of radiation techniques, radiotherapy is increasingly widely used in the treatment of hepatocarcinoma. Previous studies showed high radio-sensitivity and frequently motion of hepatobiliary zone. Although the application of magnetic resonance simulation (MR) and four-dimensional computed tomography (4D-CT) help us to clearly the gross tumor volume (GTV), accurate calculation of set-up margin is required to define the clinical to planning target volume margin. This study aimed at calculate the suitable margin between clinical target volume (CTV) and planning target volume (PTV) after the evaluation of the set-up errors using cone beam computed tomography (CBCT). <h3>Materials/Methods</h3> Patients aged 18-85 years old with pathologically diagnosed as primary hepatocarcinoma, Eastern Cooperative Oncology Group performance score ≤ 3 points, accepted the radiation recommendation by multi-disciplinary team, with only one tumor located in liver will be enrolled. Both 4D-CT and MR simulations were delivered to determine GTV. CTV was GTV plus a 5 mm margin in liver and GTV plus a 10mm margin along vessels if tumor embolus were included. PTV was CTV plus a 5mm margin. All the patients received image guided intensity modulated radiotherapy with conventional fractionation. CBCT was prescribed daily at the first week and then 2-3 times at every following week. Patients whose tumor could not be clearly classified in CBCT will be excluded. CBCT The setup errors in translational directions were recorded based on the image registration between the CBCT and the free breath CT images at simulation as reference images. Mean value and standard deviations (∑) of each patient were obtained. After that, we calculated the margin between CTV and PTV by a formula MPTV=2.5∑+0.7σ (σ means rootmeansquare of ∑). <h3>Results</h3> From November 2020 to April 2021, 35 patients fulfilled the criteria. The median age of these patients were 65 years old. The median value of GTV and PTV were 512.91 ml (45.09-1987.56 ml) and 1074.77ml (221.09-3028.40 ml), respectively. The median body mass index (BMI)was 23.98. The median CBCT times was 8 (5-12). After alignments by one senior radiation oncologist and one senior radiation therapist, we analyzed 284 sets of CBCT images. M±SD shifts in translational were 0.04±0.25 mm (LR), 0.05±0.51 mm (AP), and 0.06±0.26 mm (SI), respectively. Accordingly, the margins in LR, SI and AP directions were 5 mm, 6 mm and 10 mm, respectively. For patients whose BMI <24, the margins in LR, SI and AP directions were 4 mm, 5 mm and 12 mm. For patients whose BMI ≥24, the corresponding margins should be 6 mm,7 mm and 10 mm, respectively. <h3>Conclusion</h3> For patients with hepatocarcinoma, the setup errors were different in LR, SI and AP directions. We recommended that the margins from CTV to PTV should be 5mm, 6mm and 10 mm in LR, SI and AP directions. For patients with BMI≥24, larger margins in LR and SI directions are needed.

Early Prediction Model of Radiation-Induced Xerostomia Based on Radiomics during Radiotherapy for Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> Radiation-induced xerostomia remains one of common side effects for radiotherapy (RT) of nasopharyngeal carcinoma (NPC) and severely affects the quality of life. Early prediction of xerostomia is extremely important, but few studies mention it. We aim to build the early prediction model of xerostomia based on radiomics during RT by artificial intelligence for NPC patients. <h3>Materials/Methods</h3> Seventy-five pathologically confirmed squamous NPC patients were prospectively enrolled in our institution. All patients received a total radiation dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The patients received 3-5 cycles of cisplatin-based chemotherapy. MR images with T2-weighted (T2WI), contrast-enhanced T1-weighted (CE-T1WI) and diffusion-weighted imaging (DWI) (b = 0, 500, 800 s/mm²) were acquired on 3.0T MRI. RTOG criteria was used to evaluate xerostomia at 3 months after the completion of radiation. Delivered radiation dose of bilateral parotid and submandibular glands, MR images were collected at pre-RT, 5^th, 15^th fractions and immediately post-RT, respectively. Bilateral parotid and submandibular glands were delineated as the regions of interest (ROI) on CE-T1WI, T2WI, and DWI. We extracted a variety of features from all the images, and selected the optimal features combination by variance analysis. We built the prediction model by support vector machine (SVM). Receiver-operating characteristic (ROC) curve was used to evaluate predictive performance. <h3>Results</h3> The average age was 44.88 years (23-79 years). 24 were female and 51 were male. The mean ADC values of parotid and submandibular glands increased gradually during radiotherapy. Furthermore, the mean ADC values of salivary glands began to increase at 5^th fractions with minimal volume change. For xerostomia, 34 patients with G3-5 were categorized as toxicity cases, and 41 patients with G0-2 were classified as non-toxicity cases. Based on radiomics, clinical characteristics (sex, age, 8^th TNM staging) and radiation dose, we built 15 prediction models. Among them, the best prediction model consists of radiation dose, clinical parameters and ΔRF (the delta-radiomics features from pre-RT to 5^th fractions) which includes 6 ipsilateral parotid features, 8 contralateral parotid features, 7 ipsilateral submandibular features, and 7 contralateral submandibular features. The area under ROC curve is 0.7641, with a precision of 0.7444, a sensitivity of 0.7238, and a specificity of 0.8424. <h3>Conclusion</h3> Early prediction model including delta-radiomics, radiation dose, and clinical parameters exhibits superior sensitivity and specificity. This is an effective model for predicting xerostomia during the early stage of RT, and the clinicians could use it to adjust the treatment strategy and reduce the damage to salivary glands.

Ten-Year Follow-Up on 160 Patients Treated with Hypofractionated Prostate Salvage Radiation Therapy

<h3>Purpose/Objective(s)</h3> Patients with biochemical failure after prostatectomy are commonly treated with standard fractionation radiotherapy requiring 6.5-8 weeks of treatment. GU003 recently reported favorable short-term efficacy and acceptable toxicity using hypofractionated salvage radiotherapy after prostatectomy. However, follow-up for the study is short and questions remain regarding whether late toxicities will remain acceptable. Here, we report on long term outcomes of patients treated with a similar regimen. <h3>Materials/Methods</h3> We evaluated a consecutive cohort of patients treated from 2003-2013 with salvage RT to 65-70 Gy in 25-28 fractions using image-guided IMRT. Freedom from biochemical recurrence (FFBR), prostate cancer specific survival (PCSS), and overall survival (OS) were assessed using Kaplan-Meier analysis. Factors associated with biochemical failure were assessed using Cox regression analysis (surgical margins, Gleason score ≥8, PSA nadir, time to detectable PSA, PSA doubling time, and presalvage PSA). Late GU toxicities were scored based on a modified LENT/RTOG grading system. <h3>Results</h3> A total of 160 patients were identified with a median follow-up of 155 months. Twenty-six patients (16.3%) received androgen deprivation therapy following surgery or concurrently with radiation and 20 patients (12.5%) had lymph nodes electively treated. FFBR was 63% at 5 years and 56% at 10 years; PCSS was 99% at 5 years and 93% at 10 years; OS was 97% at 5 years and 85% at 10 years. Factors associated with increased biochemical recurrence included negative surgical margin status and higher pre-salvage PSA (p =0.025, 0.050). Total incidence grade ≥3 late toxicities was 21.9% (n=35, 33 GU, 1 GI, 1 lymphovascular) which were observed a median of 101 months after the end of radiation. There were four late grade 4 toxicities and three observed deaths potentially associated with radiation (urothelial cancer, urosepsis related to a suprapubic catheter, and pelvic sarcoma). <h3>Conclusion</h3> Prostate cancer has a long natural history as do many late RT toxicities. This cohort of patients with >10 years follow-up treated with hypofractionated salvage RT shows long-term control comparable to that seen in other salvage RT series with long-term follow-up. Although we do not have a comparator group treated with standard fractionation, these data illustrate the importance of long-term follow-up when considering toxicity from salvage RT.

Late toxicity within a Phase III clinical trial of IG-IMRT in cervix cancer (PARCER): Reanalysis with time weighted adverse event reporting (MOSES)

Background and purposeThis post-hoc analysis was performed to report the impact of Image guided intensity modulated radiotherapy (IG-IMRT) and three-dimensional conformal radiotherapy (3D-CRT) across organ system and grades of toxicity within PARCER trial (NCT 01279135). Primary endpoint of PARCER focused on grade ≥ 2 late gastrointestinal (GI) toxicity using Common Terminology Criteria for Adverse Events (CTCAE). We now analyze all adverse events using CTCAE and time and severity weighted toxicity reporting method (MOSES). Materials and methodsMOSES was calculated separately for GI, genitourinary (GU)/GI, and any late toxicities (GI, GU, lymphedema, fatigue, vaginal stenosis, fibrosis and constitutional symptoms) by imputing proportionate time weightage to CTCAE. Cumulative MOSES (C-MOSES) for multiple system and multiorgan toxicity was determined. Difference in arms was analyzed as time-to-event and intention-to-treat analysis using CTCAE grade ≥ 1 and C-MOSES ≥ 0.70. ResultsWe observed no difference in the 3-year cumulative incidence of CTCAE grade ≥ 1 GI, GI or GU, or any late toxicity between treatment arms. However, while using C-MOSES, HR of 0.59 (95% CI 0.38–0.92, p = 0.017), 0.68 (95% CI: 0.44–1.05, p = 0.08) and 0.72 (95% CI: 0.52–0.99, p = 0.04) was observed for GI, GI or GU, or any late toxicity within IG-IMRT respectively. ConclusionThis demonstrates superior discrimination of intervention effects using MOSES which demonstrates superiority of IG-IMRT.

Neoadjuvant Chemo-Radiation Using IGRT in Patients with Locally Advanced Gastric Cancer.

The goal of this study was to see how effective and safe neoadjuvant chemoradiation with image-guided IMRT was in patients with locally advanced resectable gastric cancer. Between January 2013 and June 2019, patients with locally advanced (cT3/cT4 or N+) gastric cancer treated with neoadjuvant chemoradiotherapy at PUMCH (Peking Union Medical College Hospital) were retrospectively studied. Using concurrent chemotherapy (Capecitabine alone or XELOX*2 cycles), radiotherapy (IMRT (intensity-modulated radiation therapy) 45 Gy, 25#, 5 weeks) was delivered with IGRT (image-guided radiotherapy) before the start of each weeks therapy to ensure accuracy and repeatability. A total of 95 patients were enrolled in the study, 93 (97.9%) stage cT3/T4 and 85 (89.5%) stage N+. Of these, 85 patients (89.5%) had a tumor located in the upper 1/3 of the stomach, and 93/95 patients (97.9%) completed neoadjuvant chemoradiation, with 80 patients (84.2%) undergoing stomach resection (58 D2 and 22 D1 gastrostomies). Pathology downstaging was found in 68 patients (85.0%), with 66 patients (82.5%) receiving T downstaging and 56 patients (70.0%) receiving N downstaging. There were 11 individuals (13.8%) who had a pathological complete response (PCR). The average period of follow-up was 44.7 months (19–96 months). The 5-year OS (overall survival), LRFS (local recurrence-free survival), and DMFS (distant metastasis free survival) rates of patients were 47.0% (95% CI: 38.6–55.4), 86.55% (95% CI: 79.1–93.99) and 60.71% (95% CI: 51.49–69.93%), respectively. Thirteen (13.7%) patients had grade 3–4 leukopenia, anemia, and thrombocytopenia, while 9 (9.5%) patients had grade 3–4 anemia, and 5 (5.3%) patients had grade 3–4 thrombocytopenia. PCR was found to be a significant predictive factor for OS in multivariate analysis (HR = 11.211, 95% CI: 1.500–83.813, p = 0.024). The method of using IGRT image-guided IMRT (45 Gy, 25 fractions, 5 weeks) combined with concurrent chemotherapy in patients with locally advanced resectable gastric cancer was equally effective when compared to the clinical efficacy of neoadjuvant chemoradiotherapy, with clinical outcomes achieving equal efficacy, with similar PCR rates and high rates of OS, LRFS, and DMFS, as well as good tolerances of concurrent chemoradiotherapy with acceptable side effects.

Clinical utility of a new immobilization method in image-guided intensity-modulated radiotherapy for breast cancer patients after radical mastectomy.

To investigate clinical utility of a new immobilization method in image-guided intensity-modulated radiotherapy (IMRT) for breast cancer patients after radical mastectomy. Forty patients with breast cancer who underwent radical mastectomy and postoperative IMRT were prospectively enrolled. The patients were randomly and equally divided into two groups using both a carbon-fiber support board and a hollowed-out cervicothoracic thermoplastic mask (Group A) and using only the board (Group B). An iSCOUT image-guided system was used for acquiring and correcting pretreatment setup errors for each treatment fraction. Initial setup errors and residual errors were obtained by aligning iSCOUT images with digitally reconstructed radiograph (DRR) images generated from planning CT. Totally 600 initial and residual errors were compared and analyzed between two groups, and the planning target volume (PTV) margins before and after the image-guided correction were calculated. The initial setup errors of Group A and Group B were (3.14±3.07), (2.21±1.92), (2.45±1.92) mm and (3.14±2.97), (2.94±3.35), (2.80±2.47) mm in the left-right (LAT), superior-inferior (LONG), anterior-posterior (VERT) directions, respectively. The initial errors in Group A were smaller than those in Group B in the LONG direction (P < 0.05). No significant difference was found in the distribution of three initial error ranges (≤3 mm, 3-5 mm and > 5 mm) in each of the three translational directions for the two groups (P > 0.05). The residual errors of Group A and Group B were (1.74±1.03), (1.62±0.92), (1.66±0.91) mm and (1.70±0.97), (1.68±1.18), (1.58±0.98) mm in the three translational directions, respectively. No significant difference was found in the residual errors between two groups (P > 0.05). With the image-guided correction, PTV margins were reduced from 8.01, 5.44, 5.45 mm to 3.54, 2.99, 2.89 mm in three translational directions of Group A, respectively, and from 8.14, 10.89, 6.29 mm to 2.67, 3.64, 2.74 mm in those of Group B, respectively. The use of hollowed-out cervicothoracic thermoplastic masks combined with a carbon-fiber support board showed better inter-fraction immobilization than the single use of the board in reducing longitudinal setup errors for breast cancer patients after radical mastectomy during IMRT treatment course, which has potential to reduce setup errors and improve the pretreatment immobilization accuracy for breast cancer IMRT after radical mastectomy.

Long-term outcomes of prostate intensity-modulated radiation therapy incorporating a simultaneous intra-prostatic MRI-directed boost.

Purpose/objectivesThis retrospective study demonstrates the long-term outcomes of treating prostate cancer using intensity modulated (IMRT) with incorporation of MRI-directed boost.Materials/methodsFrom February 2009 to February 2013, 78 men received image-guided IMRT delivering 77.4 Gy in 44 fractions with simultaneously integrated boost to 81–83 Gy to an MRI-identified lesion. Patients with intermediate-risk or high-risk prostate cancer were recommended to receive 6 and 24–36 months of adjuvant hormonal therapy, respectively.ResultsMedian follow-up was 113 months (11–147). There were 18 low-risk, 43 intermediate-risk, and 17 high-risk patients per NCCN risk stratification included in this study. Adjuvant hormonal therapy was utilized in 32 patients (41%). The 10-year biochemical control rate for all patients was 77%. The 10-year biochemical control rates for low-risk, intermediate-risk, and high-risk diseases were 94%, 81%, and 88%, respectively (p = 0.35). The 10-year rates of local control, distant control, and survival were 99%, 88%, and 66%, respectively. Of 25 patients who died, only four (5%) died of prostate cancer. On univariate analysis, T-category and pretreatment PSA level were associated with distant failure rate (p = 0.02). There was no grade =3 genitourinary and gastrointestinal toxicities that persisted at the last follow-up.ConclusionsThis study demonstrated the long-term efficacy of using MRI to define an intra-prostatic lesion for SIB to 81–83Gy while treating the entire prostate gland to 77.4 Gy with IMRT. Our study confirms that modern MRI can be used to locally intensify dose to prostate tumors providing high long-term disease control while maintaining favorable long-term toxicity.

Treatment outcomes in high-risk prostate cancer: a single-centre experience

Aim: The aim of that study was to evaluate the treatment results of patients with high-risk prostate cancer who received image-guided intensity-modulated radiotherapy with curative intent.&#x0D; Material and Method: Patients who underwent curative radiotherapy (RT) for high-risk prostate cancer were evaluated retrospectively in our clinic from April 2010 to April 2021. Demographics, prostate specific antigen (PSA) levels, gleason score (GS), the TNM stage of the tumor, and the success of treatment and complications were noted.&#x0D; Results: Eighty-two patients were evaluated. The mean follow-up time was 39.1 months. The mean age was 71.2±6.2 (range 50-84 years) years. The mean PSA levels of the patients was 41.1±33.8, and the median was 27 ng/ml (range 8-129 ng/ml). The mean GS of the patients was 8.3±0.6, and the median was 8 (range 7-10). The mean overall survival (OS) rate was 75.6%; survival rates for 24 months and 36 months were 91.1% and 80.4% respectively. The progression-free survival (PFS) was found to be 62.8%. Moreover, the PFS time was found to be 66,6 months. Twenty-four months and 36 months PFS rates were 83.6% and 65.4%, respectively.&#x0D; Conclusion: Intensity-modulated radiotherapy (IMRT) combined with androgen deprivation therapy is a safe and effective treatment modality for elderly patients with high-risk prostate cancer.