Pelvic Intensity-modulated Radiotherapy Research Articles

A comprehensive evaluation of toxicity after radical hysterectomy or trachelectomy and postoperative pelvic intensity-modulated radiation therapy for cervical cancer

A comprehensive evaluation of toxicity after radical hysterectomy or trachelectomy and postoperative pelvic intensity-modulated radiation therapy for cervical cancer

Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer

Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. ClinicalTrials.gov Identifier: NCT03239613.

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

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.

Efficacy and Safety of High-Dose Vitamin C Combined with Total Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer (HCCSC R02 Study).

Forpatients with locally advanced rectal cancer (LARC), the standard treatment is fluoropyrimidine (FU) -based neoadjuvant chemoradiotherapy (NCRT) combined with curative surgery. The CAO/ARO/AIO-04 trial and FORWARC trial reported that the addition of oxaliplatin to FU -based NCRT contributed to improve pathologic complete response (pCR), nevertheless, increased the acute therapeutic toxicity. Some studies showed that vitamin C (VitC) had potential benefits on anti-tumor therapy and anti-inflammatory response. Therefore, we conducted this HCCSC R02 study to explore the efficacy and safety of adding a high-dose intravenous VitC to mFOLFOX6/XELOX -based NCRT in LARC. HCCSCR02 study was designed as a prospective, single-center phase II trial, which including pts aged 18-75 years with stage II/III rectal adenocarcinoma, distance from anus ≤12cm. The enrollment criteria included: staged with MRI as cT3/cT4 or cN1/2, or mesorectal fascia involvement (MRF+), or difficult to preserve the anus. Patients with glucose-6-phosphate dehydrogenase enzyme(G6PD) deficiency were excluded. Pelvic intensity modulated radiation therapy (IMRT) was given in 45-50.4Gy/25-28 fractions. Concurrently, two cycles of chemotherapy (mFOLFOX6 or XELOX) were administered during IMRT, as well as intravenous VitC (24g) delivered daily after the end of each radiation therapy. Additional 2-3 cycles of mFOLFOX6 / XELOX were adopted between the completion of radiotherapy and surgery. The primary endpoint was pCR rate. The secondary endpoints included radiation-related toxicities, overall survival (OS) and disease-free survival (DFS). This study is still recruiting. From May 15, 2021 to Feb 8, 2023, 19 pts were recruited and finished all the scheduled NCRT, of which the proportion of cT4, cT3, cN2, cN1 were 31.6%, 63.2%, 52.6%, 36.8%, respectively. In addition, 10 pts (52.6%) were diagnosed as MRF+ initially, and 8 pts (42.1%) had a lower primary tumor(≤5cm) who were considered difficult for anal preservation before NCRT. All subjects enrolled were confirmed to be proficient mismatch repair (pMMR). As a result, 18 pts underwent a total mesorectal excision (TME) all with R0-resection, and 8 pts were evaluated as pCR (44.4%, 8/18, confidence interval: 0.246-0.663), 11 as major pathological response rate (MPR) (61.6%, 11/18), respectively. The anus preservation rate in patients with lower diseases was 87.5% (7/8). One case accepted a watch-and-wait strategy because of clinical complete response (cCR). Overall, grade 3 toxicities were observed in 4 pts, including 3 leucopenia (15.8%, 3/19), 2 neutropenia (10.5%, 2/19) and 1 diarrhea (5.3%, 1/19). No grade 4 adverse event was observed. The addition of high-dose VitC to the mFOLFOX6/XELOX-based NCRT in LARC showed a promising pCR, well tolerance, particularly low rate of diarrhea, thus warrants further investigation. NCT04801511.

Prediction of Radiomics-Based Machine Learning for Specific Dosimetric Verification of Pelvic Intensity Modulated Radiotherapy.

To establish the different machine learning classification predict models of gamma pass rates for specific dosimetric verification of pelvic intensity modulated radiotherapy plan which based on the radiomic features and to explore the best prediction model. Retrospective analysis of the 3D dosimetric verification results based on measurements with gamma pass rate criteria of 3%/2 mm and 10% dose threshold of 196 pelvic intensity-modulated radiotherapy plans was carried. Prediction models were established by extracting radiomic features data. Four machine learning algorithms, random forest, support vector machine, adaptive boosting and gradient boosting decision trees, were used to calculate the AUC value, sensitivity and specificity respectively. The classification performance of the four prediction models were evaluated. The sensitivity and specificity of the random forest, support vector machine, adaptive boosting, and gradient boosting decision trees models were 0.93,0.85,0.93,0.96, and 0.38,0.69,0.46, and 0.46, respectively. The AUC values for the random forest model and the adaptive boosting model were 0.81 and 0.82, respectively, and the AUC values for the support vector machine and gradient boosting decision tree models were 0.87. Machine learning methods based on radiomics can be used to establish a prediction model of gamma pass rate for specific dosimetric verification of pelvic intensity modulated radiotherapy. The classification performance of support vector machine model and gradient boosting decision trees model is better than that of random forest model and adaptive boosting model. The prediction model for a specific site is helpful to improve the performance of the model.

Establishment and interpretation of the gamma pass rate prediction model based on radiomics for different intensity-modulated radiotherapy techniques in the pelvis

Backgroundand objectives: Implementation of patient-specific quality assurance (PSQA) is a crucial aspect of precise radiotherapy. Various machine learning-based models have showed potential as virtual quality assurance tools, being capable of accurately predicting the dose verification results of fixed-beam intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) plans, thereby ensuring safe and efficient treatment for patients. However, there has been no research yet that simultaneously integrates different IMRT techniques to predict the gamma pass rate (GPR) and explain the model.Methods: Retrospective analysis of the 3D dosimetric verification results based on measurements with gamma pass rate criteria of 3%/2 mm and 10% dose threshold of 409 pelvic IMRT and VMAT plans was carried out. Radiomics features were extracted from the dose files, from which the XGBoost algorithm based on SHapley Additive exPlanations (SHAP) values was used to select the optimal feature subset as the input for the prediction model. The study employed four different machine learning algorithms, namely, random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM), to construct predictive models. Sensitivity, specificity, F1 score, and AUC value were calculated to evaluate the classification performance of these models. The SHAP values were utilized to perform a related interpretive analysis on the best performing model.Results: The sensitivities and specificities of the RF, AdaBoost, XGBoost, and LightGBM models were 0.96, 0.82, 0.93, and 0.89, and 0.38, 0.54, 0.62, and 0.62, respectively. The F1 scores and area under the curve (AUC) values were 0.86, 0.81, 0.88, and 0.86, and 0.81, 0.77, 0.85, and 0.83, respectively. The explanation of the model output based on SHAP values can provide a reference basis for medical physicists when adjusting the plan, thereby improving the efficiency and quality of treatment plans.Conclusion: It is feasible to use a machine learning method based on radiomics to establish a gamma pass rate classification prediction model for IMRT and VMAT plans in the pelvis. The XGBoost model performs better in classification than the other three tree-based ensemble models, and global explanations and single-sample explanations of the model output through SHAP values may offer reference for medical physicists to provide high-quality plans, promoting the clinical application and implementation of GPR prediction models, and providing safe and efficient personalized QA management for patients.

Application of short-course radiotherapy with total neoadjuvant therapy in the treatment of middle and low rectal cancer

Objective: To compare the efficacy and safety of short-course radiotherapy with total neoadjuvant therapy (SCRT-TNT) and neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced middle and low rectal cancer. Methods: A retrospective cohort study was carried out. A of 126 patients with locally advanced middle and low rectal cancer who were treated in the Department of Gastrointestinal Cancer Surgery of Fujian Cancer Hospital from September 2016 to March 2020 were enrolled, including 73 males and 53 females, with a mean age of (56.5±9.8) (23-77) years. Based on neoadjuvant regimen (nCRT treatment was performed before December 2018 and SCRT-TNT treatment was carried out after January 2019), patients were divided into nCRT group (n=68) and SCRT-TNT group (n=58). There were no statistically significant differences in age, sex, distance from tumor to anal verge, Eastern Cooperative Oncology Group (ECOG) performance status and clinical TNM stage between the two groups (all P>0.05). Patients in both groups received pelvic intensity-modulated radiotherapy (IMRT). The radiotherapy dose of nCRT group was 50Gy/25 times/5 weeks. Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation. However, patients in SCRT-TNT group received CapeOX regimen (oxaliplatin+capecitabine) for 2 cycles of induction chemotherapy, followed by short-course radiotherapy (25Gy/5 times/5 days), then underwent a radical surgery two weeks after completion of consolidation chemotherapy (4 cycles). The adverse reactions, perioperative safety and efficacy of neoadjuvant therapy were compared and analyzed between the two groups. Results: Both groups completed neoadjuvant therapy as planned. Patients in nCRT group and SCRT-TNT group had similar incidence of adverse reactions to radiotherapy and chemotherapy, however, there were no statistically significant differences in the incidence of surgical complications, operation time, intraoperative blood loss and postoperative length of hospital stay (all P>0.05). A total of 119 patients underwent total mesenterectomy (TME), including 64 patients in the nCRT group and 55 patients in the SCRT-TNT group, all with R0 resection. The pathological complete response (pCR) rate was 10.9% (7/64) in the nCRT group and 25.5% (14/55) in the SCRT-TNT group, respectively, with a statistically significant difference (P=0.038). Two years after surgery, there was no statistically significant difference in local recurrence rate and overall survival rate between the two groups (both P>0.05). However, the clinical metastasis rate of SCRT-TNT group was significantly lower than that of nCRT group (20.3% vs 9.1%), with a statistically significant difference (P<0. 05). Conclusion: SCRT-TNT do not increase the adverse reactions of radio chemotherapy and perioperative risks in the treatment of locally advanced middle and low rectal cancer, and the tumor regression effect is good, which is worthy of clinical promotion.

Effect of Pelvic Bone Marrow Dose-Volume Parameters on Acute Hematologic Toxicity in Neoadjuvant Pelvic Intensity-Modulated Radiotherapy for Local Advance Rectal Cancer

<h3>Purpose/Objective(s)</h3> Neoadjuvant concurrent chemoradiotherapy effectively improves survival and local control of locally advanced rectal cancer (LARC). However, because the pelvic bone marrow is inevitably irradiated, pelvic radiotherapy often results in varying degrees of acute hematologic toxicity (HT). To effectively control the risk of acute HT, this study analyzed the correlation between the volume of irradiated pelvic bone marrow and acute HT based on clinical cases, and identified the corresponding risk threshold. <h3>Materials/Methods</h3> From October 2017 to May 2019, 41 LARC patients who received neoadjuvant CRT were retrospectively reviewed in our center. All patients were treated with 5-field intensity-modulated radiotherapy (IMRT), and the prescription dose delivered to PTV was 45∼50.4 Gy in 25∼28 fractions. Capecitabine or 5-fluorouracil were administered daily 5 days a week during radiotherapy. Different HT were recorded according to National Cancer Institute Common Toxicity Criteria Version 3.0 (NCI‐CTC.V3.0) based on laboratory tests. Multivariable logistic regression was performed to evaluate the association between the volume of irradiated pelvic bone marrow and different HT. Generalized additive model (GAM) and piecewise linear regression were used to further analyze the possible non-linear relationship and threshold effect between them. <h3>Results</h3> Multivariate Logistic regression analysis showed that low-dose (5,10,15,20 Gy) of irradiated total pelvic bone marrow volume (TVx) and coxal bone marrow volume (CVx) were significantly correlated with ≥I grade hemoglobin decreased, ≥I grade neutropenia and ≥II grade leukopenia. There was a significant negative correlation between the irradiated sacrum bone marrow volume (SVx) and ≥I grade hemoglobin decreased, ≥II grade leukopenia. Threshold effect has been observed between CV₅, CV₁₀, CV₁₅ and ≥I grade neutropenia by Generalized additive model (GAM) and piecewise linear regression, and the thresholds were 597ml, 575ml, 518ml, OR (95%CI) were 1.86 (1.04, 3.33), 2.36 (1.13, 4.94), 1.57 (1.08, 2.29), respectively. The thresholds between CV₅, CV₁₀ and ≥II grade leukopenia was 595ml, 575ml, OR (95%CI) was 1.86 (1.06, 3.25), 1.85(1.08, 3.16), respectively. <h3>Conclusion</h3> In neoadjuvant IMRT of rectal cancer, CV is a better predictor of acute HT induced by concurrent chemoradiotherapy than TV. The irradiated volume of CV associated with acute HT was mainly low dose levels (CV₅, CV₁₀, CV₁₅, CV₂₀). In order to effectively reduce the risk of acute HT, keeping CV₁₀ within 575ml may be a good choice.

Long-Term Follow-Up Results of Adjuvant Intensity-Modulated Radiotherapy with Concurrent Paclitaxel and Cisplatin in High-Risk Endometrial Cancer Patients.

Purpose The purpose of this study was to retrospectively review the outcomes of patients with high-risk endometrial cancer treated with adjuvant radiotherapy with concurrent paclitaxel and cisplatin (TP). Methods Patients with endometrial cancer who underwent radical surgery were screened between Jan 2005 and Dec 2018. Patients with high-risk factors who received adjuvant chemoradiotherapy were included in the study. High risks included stage I, endometrioid-type grade 3 with deep myometrial invasion or lymphovascular space invasion (or both), endometrioid-type stage II to IVa, or stage I to III with serous or clear cell histology. The adjuvant treatment regimen included one cycle of TP chemotherapy, followed by pelvic intensity-modulated radiotherapy (IMRT) with concurrent TP, followed by an additional one cycle of TP. Failure free survival (FFS) and overall survival (OS) were estimated. Patterns of recurrence and occurrence of adverse events were described. Results A total of 450 patients with high-risk endometrial cancer were screened, 231 of whom were included in this study. After a median follow-up of 70 months, the 5-year OS was 94.7%, and the 6-year OS was 91.8%. The 5-y and 6-y FFS were 90.8% and 87.9%, respectively, which were related to stage (P < 0.05). A total of 14 patients experienced tumor recurrence, including 7 pelvic recurrence and 7 distant metastases. Seven patients died, all due to tumor progression. A total of 164 patients (71%) completed the prescribed course of treatment. A total of 205 patients had adverse events, 46 patients (20%) had grade 1, 92 patients (40%) had grade 2, 49 patients (21%) had grade 3, and 18 patients (8%) had grade 4. There were 83 nonhematologic and 122 hematologic toxicities (26 grade 3 and 18 grade 4). Conclusion Adjuvant pelvic radiotherapy combined with synchronous TP chemotherapy can achieve excellent long-term survival for high-risk endometrial cancer patients. Moreover, this combination therapy has good safety and feasibility, which is worthy of further study and verification.

Clinical analysis of prophylactic para-aortic intensity-modulated radiation in cervical cancer

This study aimed to compare the survival and toxicity of patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIIC cervical cancer without common iliac node metastasis treated with extended-field intensity-modulated radiotherapy (EF-IMRT) or pelvic IMRT (P-IMRT). Thirty-one patients treated with EF-IMRT and 37 patients who underwent P-IMRT were analysed retrospectively. Both groups were treated with high-dose-rate 192Ir two-dimensional brachytherapy and concurrent chemotherapy. The chi-square test and Kaplan-Meier method were used to compare toxicity and survival between the two groups. The median follow-up time of EF-IMRT group and P-IMRT group was 22 and 30 months, respectively. The 3-year overall survival (OS), progression-free survival (PFS), and para-aortic lymph node metastasis-free survival (PAMFS) in the EF-IMRT group and P-IMRT group were 87% versus 74.6%, 83.6% versus 61.7%, and 96% versus 80.5%, respectively. Treatment regimens, tumour size, and radiation time were independent prognostic factors of OS and PFS. Treatment regimens, tumour size, and total equivalent dose in 2 Gy/f (EQD2) of point A were independent prognostic factors of PAMFS. Five patients in the EF-IMRT group and 14 patients in P-IMET group experienced treatment failure. The cumulative incidence of grade 3 and 4 acute leukopenia in the EF-IMRT group was 51.6%, in comparison with 27.03% in the pelvic group. No difference was found in thrombocytopenia between two groups. Patients with FIGO 2009 stage IB1-IIIC cervical cancer without common iliac node metastases may be benefit from EF-IMRT. Notably, EF-IMRT exhibits increased toxicity incidence; however, this remains within an acceptable range.

Gamma Passing Rate – Correlation with Patient Specific Quality Assurance Devices using Two Photon energies in Pelvic IMRT

The effect on Gamma Passing Rate is studied by changing the Photon Energy in the Patient Specific Quality Assurancein Pelvic IMRT using EPID and MatriXX keeping PSQA device at Isocenter. Dose verification of 62 patients, sufferingfrom pelvic malignancies and treated with Intensity modulated radiation therapy (IMRT), with EPID and MatriXX usinggamma criteria of 3%/3 mm, 3%/2 mm, 2%/3 mm, 2%/2 mm and investigated the effect on Gamma Passing Rate (%GP) bychanging beam energy from 6 MV to 10 MV. The results demonstrated that the behavior of gamma passing rate decreases ascriteria is changed from 3%/3 mm to strict criteria. The mean gamma passing rate for 6 MV beam were (%GP±StandardDeviation σ) 99.64±0.81, 99.45±1.08, 97.57±2.12, 96.17±2.63 using the criteria 3%/3 mm, 3%/2 mm, 2%/3 mm, 2%/2 mmrespectively in EPID. For MatriXX, the mean %GP were 96.69±4.11, 93.85±5.31, 88.17±10.63, 82.2±12.28 respectively.For 10 MV, the mean (%GP±Std. Dev) were 99.64±0.81, 99.45±1.08, 97.57±2.12, 96.17±2.63 for in EPID, 96.69±4.11,93.85±5.31, 88.17±10.63, 82.2±12.28 for MatriXX respectively. Difference between %GP for 6 MV and 10 MV beam were-0.01, -0.11, 1.08, 1.61 with gamma criteria of 3%/3 mm, 3%/2 mm, 2%/3 mm, 2%/2 in EPID. For MatriXX, differencebetween %GP for 6 MV and 10 MV beam were -0.40, -0.24, 0.96, 1.62 respectively. It can be concluded that applying morestrict gamma criteria results in low gamma passing rate. There is marked difference in Gamma Passing Rate (%GP) withchange in photon energy.

Changes of immune microenvironment before and after chemoradiotherapy in cervical cancer.

e17503 Background: Cervical cancer is the fourth most common cancer in women worldwide. Metastasis and invasion of cervical cancer are closely related to the tumor microenvironment. As an effective treatment, chemoradiotherapy plays a vital role in immune-related cells and factors. However, little is known about the effect of chemoradiotherapy on the immune microenvironment in cervical cancers. Therefore, we studied the immune microenvironment alterations before and after chemoradiotherapy and analyzed their prognostic significance in cervical cancer patients. Methods: We recruited 15 patients with stage IB1-IVA cervical squamous cell carcinoma. Pelvic intensity-modulated radiotherapy (IMRT) was performed with conventional segmentation of 2Gy per irradiation (IB3 stage was treated with synchronous cisplatin for weeks), FFPE samples pre-treatment, and one-week after-chemoradiotherapy were conducted an exploratory biomarker analysis based on gene expression profiling (GEP). The panel of 289 genes was customized based on critical genes and pathways during tumor immunoregulation (e.g., tumor antigen release, T cell activation, and immune metabolism). The differential expressed genes between these two groups were then assessed. Results: Forty-two genes were found to be differentially expressed, with 21 genes having &gt; 1.5-fold mean expression difference after chemoradiotherapy. Analysis of important GO terms and KEGG pathways indicated that the pathways enriched by different genes are located in immune-related pathways, specifically, T cell activation (GO-BP), cytokine activity (GO-MF), and cytokine-cytokine receptor interaction (KEGG). After-chemoradiotherapy, the enrichment of tumor-infiltrating lymphocytes (TILs) varied greatly, especially the macrophages. Conclusions: This study preliminarily demonstrated that chemoradiotherapy caused the release of pro-inflammatory like CCR7 and CD69 and immune cell (macrophages) infiltration alterations after chemoradiotherapy in cervical cancer patients.

Comparison between Pelvic IMRT and 3D-CRT in Combination with Chemotherapy via Nrf2 Expression on the High-Risk Endometrial Cancer.

This study aimed to explore the clinical efficacy of pelvic intensity-modulated radiation therapy (IMRT) and 3-dimensional conformal radiotherapy (3D-CRT) in combination with chemotherapy on high-risk endometrial cancer. The effect of these methods is evaluated via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, the levels of chitinase protein 40 (YKL-40), human epididymis protein 4 (HE4), and prolactin (PRL) in serum. For this purpose, between August 2014 and July 2017, 114 endometrial cancer patients admitted to this hospital for treatment were randomized into the observation group (n=60) and control group (n=54). Following the surgery, patients in these two groups received the chemotherapy of taxol and carboplatin (TC). Based on the chemotherapy, patients in the observation underwent the IMRT, while those in the control group adopted the 3D-CRT. The Nrf2 expression was performed based on the Real-time PCR technique. The incidence rate of adverse reactions was a 3-year recurrence rate and mortality rate. Results showed that after treatment, levels of YKL-40, HE4, and PRL in the serum of patients in two groups decreased compared to those before treatment (all P < 0.05). In comparison, the difference between the two groups showed no statistical significance (P > 0.05). The evaluation of Nrf2 transcription factor expression showed significant differences started in comparisons of the Nrf2 Expression between two groups (P > 0.05), and this enhancement was significant in the control group after treatment. Comparison of the incidence rates of the bone marrow suppression during treatment showed no significant difference (P > 0.05). However, the incidence rates of radiation enteritis and radio-cystitis in the observation group were much lower than those in the control group (P < 0.05). During the follow-up, there were five patients in the control group and 7 in the observation group losing to the follow-up, and among the remaining subjects, no significant difference was identified in the comparison of the recurrence rate or mortality rate between the two groups (all P > 0.05). In general, Pelvic IMRT in combination with chemotherapy is a promising and safe candidate for high-risk endometrial cancer with mild radiation injury; besides, YKL-40, HE4, and PRL are the effective indicator for the prediction of efficacy in chemotherapy for endometrial cancer.

Clinical Implication of Simultaneous Intensity-modulated Radiotherapy Boost to Tumor Bed for Cervical Cancer with Full-thickness Stromal Invasion.

ObjectiveThe objective of this study was to retrospectively explore the clinical implications of simultaneous intensity-modulated radiotherapy (IMRT) boost to the tumor bed in cervical cancer with full-thickness stromal invasion (FTSI).Patients and MethodsPatients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB and IIA cervical cancer with confirmed FTSI were included. Patients received pelvic IMRT from a dose of 50.4 Gy in 28 fractions with (or without) a simultaneous integrated boost (SIB) to 58.8 Gy in 28 fractions for the tumor bed. The progression-free survival (PFS), overall survival (OS), and pelvic-PFS (p-PFS) were analyzed using the Kaplan–Meier method, and independent prognostic factors were explored by Cox regression analyses.ResultsPatients without a tumor bed boost had a poor prognosis. The 5-year OS was 81.3% versus 58.3% and the 5-year PFS rates were 75.0% versus 57.6% (boost vs non-boost). The FIGO stage, pathology, adjuvant chemotherapy, and tumor bed boost were independent factors affecting both the 5-year OS and PFS. Subgroup analysis showed that the SIB group had a higher 5-year OS, PFS, and p-PFS for different stages, lymph node status, and risk groups than the non-SIB group. Recurrence occurred in 268 of 910 (29.5%) patients without SIB and 49 of 293 (16.7%) with SIB. Among patients with recurrence, 113 of 282 (40.1%) in the non-boost group compared with 14 of 51 (23.0%) patients in the boost group had a pelvic recurrence. Tumor bed boost resulted in an increase in the mean radiation dose to the intestine, rectum, and bladder, although there were no differences in the rates of acute and late toxicities between the 2 groups.ConclusionTumor bed boost by external beam radiotherapy (EBRT) is an effective and safe method for patients with FTSI and risk factors. Compared with the standard prophylactic radiation, tumor bed boost by EBRT was not associated with increased acute and late toxicities.

Endostar, an Antiangiogenesis Inhibitor, Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer.

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p = 0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p = 0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

101: A Single Institution Retrospective Study of Pelvic Insufficiency Fractures Following Curative-Intent Pelvic Intensity-Modulated Radiation Therapy for Gynecologic, Gastrointestinal and Genitourinary Cancers

101: A Single Institution Retrospective Study of Pelvic Insufficiency Fractures Following Curative-Intent Pelvic Intensity-Modulated Radiation Therapy for Gynecologic, Gastrointestinal and Genitourinary Cancers

A phase I/II study of acute and late physician assessed and patient-reported morbidity following whole pelvic radiation in high-risk prostate cancer patients

Background The aim of this study was to assess acute and late morbidity measured by the physician and patient-reported outcomes (PROs) in high-risk prostate cancer (PC) patients receiving whole pelvic intensity-modulated radiotherapy (IMRT) in the setting of a national clinical trial. Material and methods A total of 88 patients with adenocarcinoma of the prostate and high-risk parameters were enrolled from 2011 to 2013. All patients received 78 Gy in 39 fractions of IMRT delivering simultaneous 78 Gy to the prostate and 56 Gy to the seminal vesicles and lymph nodes. Physician-reported morbidity was assessed by CTCAE v.4.0. PROs were registered for gastro-intestinal (GI) by the RT-ARD score, genito-urinary (GU) by DAN-PSS, sexual and hormonal by EPIC-26, and quality of life (QoL) by EORTC QLQ-C30. Results Median follow-up (FU) time was 4.6 years. No persistent late CTCAE grade 3+ morbidity was observed. Prevalence of CTCAE grade 2+ GI morbidities varied from 0 to 6% at baseline throughout FU time, except for diarrhea, which was reported in 19% of the patients post-RT. PROs revealed increased GI morbidity (≥1 monthly episode) for "rectal urgency", "use of pads", "incomplete evacuation", "mucus in stool" and "bowel function impact on QoL" all remained significantly different (p < .05) at 60 months compared to baseline. CTCAE grade 2+ GU and sexual morbidity were unchanged. GU PROs on obstructive and irritative GU items (≥daily episode) increased during RT and normalized at 24 months. No clinically significant differences were found in sexual, hormonal, and QoL scores compared to baseline. Conclusions Whole pelvic RT resulted in a mild to the moderate burden of late GI morbidities demonstrated by a relatively high prevalence of PROs. Whereas, physician-assessed morbidity revealed a low prevalence of late GI morbidity scores. This emphasizes the importance of using both PROs and physician-reported scoring scales when reporting late morbidity in clinical trials.

Long-term safety of high-dose whole pelvic IMRT for high-risk localized prostate cancer through 10-year follow-up.

The aim of this study was to evaluate the long-term efficacy and safety of whole pelvic intensity-modulated radiation therapy with a simultaneous-integrated boost (WP-SIB-IMRT) for locally advanced prostate cancer (LAPCa). All patients with cT3-4N0M0 prostate cancer treated with WP-SIB-IMRT between February 2006 and September 2009 at our institution were analyzed retrospectively. The prescribed dose was 78Gy to the prostate and 58.5Gy to the prophylactic pelvic lymph nodal area in 39 fractions delivered using the simultaneous-integrated boost technique. All patients received short-term neoadjuvant androgen-deprivation therapy alone (median 8.3months). Propensity-score matching (PSM) analysis was performed to evaluate the additional benefit of prophylactic whole pelvic radiation therapy (WPRT), using the cohort of 203 LAPCa patients treated with prostate-only IMRT (PO-IMRT). In total, 47 consecutive patients were analyzed. The median estimated risk of pelvic lymph node involvement was 57.5%. The median follow-up period was 10.5years. The 10year prostate cancer-specific survival and biochemical failure (BF) rates were 92.2 and 54.8%, respectively. The 10year cumulative incidence rates of ≥ grade 2 late genitourinary and gastrointestinal toxicities were 21.6 and 17.2%, respectively. From a total of 250 patients, PSM analysis identified 76 patients with similar characteristics, and no significant difference in BF rates was observed between WP-SIB-IMRT and PO-IMRT cohorts (p = 0.261). WP-SIB-IMRT for LAPCa was safe over long-term observation, although no clear benefit of WPRT was observed among our small and highly selected cohort. Regarding the additional efficacy of WPRT, further investigations are needed.

Post-operative small pelvic intensity-modulated radiation therapy for early-stage cervical cancer with intermediate-risk factors: efficacy and toxicity.

The aim of the present study was to retrospectively evaluate the toxicity and efficacy of post-operative small pelvic intensity-modulated radiotherapy in early-stage cervical cancer patients with intermediate-risk factors. Between 2012 and 2016, 151 patients who had cervical cancer (International Federation of Gynecology and Obstetrics stage I-IIA) with intermediate-risk factors were treated with post-operative small pelvic intensity-modulated radiotherapy. The median dose of 50.4Gy in 28 fractions with small pelvic intensity-modulated radiotherapy was prescribed to the planning target volume. The intensity-modulated radiotherapy technique used was conventional fixed-field intensity-modulated radiotherapy or helical tomotherapy. The median follow-up was 37months. The 3-year disease-free survival and overall survival rates were 89 and 96%, respectively. A total of 144 patients (95.3%) were alive at the last follow-up. In total, 6 patients (3.9%) had recurrence: locoregional recurrence in 3 patients (2%), distant metastasis in 2 (1.3%), and both in 1 (0.6%). Diarrhoea was the most common acute toxicity. There were no patients suffering from acute or late grade≥3 toxicity. Only 4 patients (2.6%) had late grade 2 toxicities. For early-stage cervical cancer patients with intermediate-risk factors, post-operative small pelvic intensity-modulated radiotherapy was safe and well tolerated. The rates of acute and late toxicities were quite satisfactory.