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PURPOSE: The purpose of this planning study was to develop an acceptable technique for highly hypofractionated intensity-modulated radiation therapy using simultaneous integrated boost technique (SIB-hHF-RT) for nonmetastatic National Comprehensive Cancer Network high-risk prostate cancer. MATERIALS AND METHODS: We created SIB-hHF-RT plans for 14 nonmetastatic prostate cancer patients with MRI-detectable intraprostatic lesions (IPLs) and without intestines locating close to the seminal vesicle and prostate. We prescribed 57Gy for IPLs and 54Gy for the remainder of planning target volume (PTV) in 15 fractions. The IPLs were contoured based on magnetic resonance imaging, and PTV was generated by adding 6-8-mm margins to the clinical target volume. For the dose-volume constraints of organs at risk (OARs), the same constraints as 54Gy plans were used so as not to increase the toxicity. RESULTS: All created plans fulfilled the dose-volume constraints of all targets and OARs. The median estimated beam-on time was 108.5s. For patient-specific quality assurance, the global gamma passing rates (3%/2mm) with 10% dose threshold criteria were greater than 93% in all cases and greater than 95% in 11 cases. CONCLUSION: SIB-hHF-RT plans were developed that fulfill the acceptable dose-volume constraints and pass patient-specific quality assurance. We believe these plans can be applied to selected patients with nonmetastatic prostate cancer.

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.

Purpose To evaluate feasibility and outcome of our institutional SIB-IMRT schedule in patients with anal cancer and to selectively review the literature on different SIB-IMRT schedules. Patients and methods Between 01/08-06/13 25 patients with biopsy proven squamous cell anal cancer were treated in our institution with IMRT. Radiotherapy was delivered in two series using a SIB-IMRT schedule of 45 Gy/1.8 Gy to the primary tumor and adjacent pelvic lymph nodes and 38 Gy/1.52 Gy to elective nodes followed by an IMRT boost of 7×2 Gy = 14 Gy to the primary tumor and involved nodes (cumulative prescription dose: 59 Gy). Results Mean follow-up was 20 months (range: 4-68). The 2-year-local control, colostomy-free survival, distant metastases-free survival and overall survival rates were 92%, 92%, 92%, and 88%, respectively. Grade 3 acute skin toxicity was observed in 6 patients (24%). No high grade gastrointestinal or urinary acute toxicity occurred. Four patients required more than one day of treatment interruption due to acute toxicity. No grade 3 or higher late sequelae were observed. Conclusion We present our institutional SIB-IMRT experience treating patients with anal cancer in two series using moderate single doses from 1.5-2.0 Gy. Our results, in terms of loco-regional outcome and toxicity, were comparable to other studies. The incidence of treatment interruptions was very low. Therefore this schedule appears to be safe for clinical use.

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).