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Peng Cai, Yan Yang, Duo-Jie Li Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of ChinaCorrespondence: Duo-Jie LiDepartment of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, No. 287 of Changhuai Road, Bengbu, 233004, People’s Republic of ChinaTel +86 13956332626Email liduojie123@163.comPurpose: Use of simulated integrated boost-intensity-modulated radiation therapy (SIB-IMRT) is rarely reported in the treatment of esophageal cancer. This study was performed to observe the curative effect and prognostic factors associated with concurrent chemoradiotherapy for esophageal cancer using modern radiotherapy (RT) techniques.Patients and Methods: In total, 315 patients with esophageal squamous cell carcinoma who received SIB-IMRT between 2015 and 2018 were included in this retrospective study. Median doses were planning target volume (PTV) 5400 cGy, 30 times (180cGy/fraction); planning gross tumor volume (PGTV) 6000 cGy, 30 times (200 cGy/fraction), once a day and 5 times a week. The entire period of RT was 6 weeks. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse reactions were observed. Univariate analysis was performed, and factors with P< 0.15 were included in multivariate analysis. Cox regression analysis was used for multivariate prognostic analysis. P< 0.05 was considered statistically significant. The incidence of adverse reactions under single chemotherapy concurrent chemoradiotherapy (sCCRT) and double chemotherapy concurrent chemoradiotherapy (dCCRT) was analyzed.Results: Two-year, 3-year OS and PFS of the entire group were 49.5%, 40.2% and 40.3%, 34.0%, and the median survival time was 23.5 months. Univariate and multivariate analyses showed that T-stage (P=0.049), N-stage (P=0.024), clinical stage (P=0.041), short-term efficacy (P< 0.001), and use of concurrent chemotherapy (P< 0.001) were the influencing factors for OS. ORR was 87.6%. Adverse reactions were significantly increased with increasing chemotherapy dose.Conclusion: The adverse reactions of SIB-IMRT in esophageal cancer can be tolerated. T-stage, N-stage, clinical stage, short-term curative effect, and concurrent chemotherapy are the prognostic factors affecting survival. Because it has lower toxicity and is as effective as dCCRT, sCCRT should be considered in the management of esophageal cancer.Keywords: esophageal neoplasm, prognosis, intensity-modulated radiotherapy, SIB-IMRT

Background To explore the maximum tolerated dose (MTD) and evaluate the safety of dose escalation using hypofractionated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) concurrent with chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC). Methods Four escalating radiation dose levels were used. This study included 25 patients with previously untreated NSCLC who received six concurrent weekly chemotherapy cycles comprising cisplatin and docetaxel. Dose-limiting toxicity (DLT) was defined as any acute toxicity that interrupted radiotherapy for more than 1 week. MTD was defined as the highest dose level that didn’t induce DLT or grade 5 toxicity in two patients. Results All 25 patients received the prescribed escalating radiation dose from the start dose up to LEVEL 4. Two patients experienced DLT at dose LEVEL 4. One patient died because of upper gastrointestinal hemorrhage within 6 months after radiotherapy, whereas another patient among the additional five patients died because of grade 5 radiation pneumonitis within 2 months after radiotherapy. Dose LEVEL 3 was defined as MTD. The 1- and 2-year local controls were 82.8 and 67.8%, respectively. The median progression-free survival was 15.4 months, whereas the median overall survival was 27.3 months. Conclusions Dose escalation was safely achieved up to LEVEL 3 [the planning gross target volume (PTVG) 60.5 Gy/22 Fx, 2.75 Gy/Fx; the planning clinical target volume (PTVC) 49.5 Gy/22 Fx] using SIB-IMRT concurrently with chemotherapy for unresectable stage III NSCLC, and the acute toxicities were generally well tolerated. Further prospective studies on long-term outcomes and late toxicities are warranted. Trial registration Retrospective registration, ChiCTR1900027290(08/11/2019).

Local tumor failure remains a major problem after radiation‐based nonsurgical treatment for unresectable locally advanced nonsmall cell lung cancer (NSCLC）and inoperable stage II NSCLC. The aim of this study was to evaluate the feasibility of simultaneous integrated boost of intensity‐modulated radiation therapy (SIB‐IMRT) to stage II‐III NSCLC with metastatic lymph nodes (ChiCTR 2000029304). Patients were diagnosed by pathology or PET‐CT. PTV was divided into two parts as follows, the PTV of primary tumor (PTVp) and the PTV of metastatic lymph nodes (PTVn). The radiotherapy doses were simultaneously prescripted 78 Gy (BED = 101.48 Gy) for PTVp and 60‐65 Gy (BED = 73.6‐81.25 Gy) for PTVn, 26f/5.2 weeks. Response was scored according to WHO criteria. Radiotherapy toxicity was scored according to RTOG criteria. Hematology and gastrointestinal toxicity were scored according to CTCAE1.0 criteria. A total of 20 patients were enrolled. Seventeen patients were diagnosed by pathology and three patients were diagnosed by PET‐CT. All patients were treated with SIB‐IMRT. The objective response rate (ORR) was 90%, with CR 25%, PR 65%, NC 10%, and PD 0%. Although radiotherapy toxicity was common, there were no grade ≥3, with radiation pneumonitis (10 cases), esophagitis (17 cases), and dermatitis (12 cases). The local control rates at 1, 3, and 5 years were 85%, 75%, and 70%, respectively. The overall survival（OS）and local progression‐free survival (LPFS) rates at 1, 3, and 5 years were 90%, 42.6%, and 35.5% and 84.4%, 35.5%, and 28.4%, respectively. SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety, and satisfactory efficacy. However, due to the limitation of small sample, these findings are needed to confirm by future trials with a larger sample size., The different radiation doses were simultaneously prescripted 78 Gy (PTVp）and 60‐65 Gy (PTVn). SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety and satisfactory efficacy.

Supplemental Digital Content is available in the text, Background: The optimal intensity modulated radiation therapy (IMRT) technique for head and neck cancer (HNC) has not been determined yet. The present study aimed to compare the clinical outcomes of the simultaneous integrated boost (SIB)-IMRT versus the sequential boost (SEQ)-IMRT in HNC. Methods: A meta-analysis of 7 studies involving a total of 1049 patients was carried out to compare the treatment outcomes together with severe acute adverse effects of the SIB-IMRT versus the SEQ-IMRT in HNC patients. Results: Comparison of the SIB-IMRT and SEQ-IMRT showed no significant difference in the measurement of overall survival (OS) (hazard ratio [HR] 0.94; 95% confidence inerval [CI], 0.70–1.27; P = .71), progression free survival (PFS) (HR 1.03; 95% CI, 0.82–1.30; P = .79), locoregional recurrence free survival (LRFS) (HR 0.98; 95% CI, 0.65–1.47; P = .91), and distance metastasis free survival (DMFS) (HR 0.87; 95% CI, 0.50–1.53; P = .63). Moreover, there were no significant differences in adverse effect occurrence between the SIB-IMRT and SEQ-IMRT groups. Conclusion: SIB-IMRT and SEQ-IMRT can provide comparable outcomes in the treatment of patients afflicted by HNC. Both IMRT techniques were found to carry a similar risk of severe acute adverse effect. SIB-IMRT may have advantages due to its convenience and short-course of treatment; however, the optimum fractionation and prescribed dose remained unclear. Furthermore, both IMRT techniques can be advocated as the technique of choice for HNC. Treatment plan should be individualized for patients.

To increase the efficacy of radiotherapy for non-small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new "toxicity index" (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V-20 in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC. (C) 2014 American Association of Medical Dosimetrists.

The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8–20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution was as follows: stage I, 1 (2.9%); stage III, 14 (41.2%); and stage IV, 19 (55.9%). All patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64–68 Gy in 29–31 fractions to the nasopharyngeal gross target volume. Within the median follow-up of 52 months (range, 9–111 months), 1 patient (2.9%) experienced local recurrence and 4 (11.8%) developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due to recurrence or metastasis. The 5-year locoregional relapse–free survival, distant metastasis–free survival, disease-free survival, and overall survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3–4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed grades 1–2 xerostomia and ototoxicity, respectively. Two patients (8.3%) developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.

Aim: To report the acute toxicity of a hypofractionated regimen of intensity-modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) to the pelvic nodes and the prostatic bed after radical prostatectomy. Patients and Methods: Patients with prostate adenocarcinoma at high risk of relapse after radical prostatectomy or with biochemical relapse were deemed eligible for study. SIBIMRT was prescribed to the whole pelvis (45-Gy delivered in 1.8-Gy fractions) and the prostatic bed [62.5 Gy, 2.5-Gy fractions, Equivalent Dose in 2-Gy fraction (EQD2)=68.75 Gy, a/β=3]. Acute toxicity was recorded and graded according to Radiation Therapy Oncology Group (RTOG) criteria. Results: Forty-nine patients were enrolled. No cases of grade =3 acute toxicity were recorded. Grade 2 acute genitourinary and gastrointestinal toxicity was observed in 9.6% and 29.7% of patients, respectively. Conclusion: After radical prostatectomy, hypofractionated high-dose SIB-IMRT enables for reduction of the overall treatment time, with an acute toxicity profile which compares favourably with that of conventionally fractionated high-dose three-dimensional conformal radiotherapy (3D-CRT).