Intensity-modulated Radiotherapy With Simultaneous Integrated Boost Research Articles

Can intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) replace consolidation brachytherapy in the curative treatment of cervical cancer? A dosimetric study

Can intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) replace consolidation brachytherapy in the curative treatment of cervical cancer? A dosimetric study

Long term outcome and late toxicity Of SIB-IMRT in definitive management of head and neck cancers in patients not suitable for chemo-radiotherapy.

To evaluate efficacy and late toxicity of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) in definitive management of head-and-neck cancers. In this prospective interventional study, histological proven squamous cell carcinoma of oropharynx, hypopharynx, or larynx with stage T1-3 N0-3 M0 who were not candidates for concurrent chemotherapy were treated with IMRT-SIB with radical intent. Doses prescribed for IMRT-SIB to meet the clinical needs of nodal volumes were either SIB-66 schedule 66 Gray (Gy) prescribed to high risk (HR) planned target volume (PTV), 60 (Gy) to intermediate risk (IR) PTV and 54 Gy to low risk (LR) PTV in 30 fractions or SIB-70 schedule 70 Gy to PTV-HR, 59.4 Gy to PTV-IR and 56 Gy to PTV-LR in 33 fractions. Forty-five patients were included. Forty-two patients were treated with SIB-66 schedule and three patients with SIB-70 schedule. The median follow-up period was 21 (6-68) months. There was residual disease in three patients. Recurrence was observed in 24 patients. Most recurrences were in HR volume (n = 19) and three patients had distant failure. Estimated 2-year locoregional control, disease-free survival, and overall survival were 55.55%, 49.7%, and 51.1%, respectively. Grade 3 late skin toxicity, subcutaneous fibrosis, and xerostomia were observed in three patients. Efficacy and late toxicity of IMRT-SIB observed in our study suggest it as a suitable treatment option for patients who are not fit for chemoradiation.

Multiparametric MRI-guided Hypofractionated Intensity-modulated Radiation Therapy With Simultaneous Integrated Boost for Glioblastoma

This study investigated the feasibility and efficacy of multiparametric magnetic resonance imaging (MRI)-guided dose-escalated hypofractionated intensity-modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) for glioblastoma. Eighteen patients underwent postoperative IMRT-SIB for glioblastoma using three MRI sequences: double inversion recovery (DIR), diffusion tensor imaging (DTI), and post-gadolinium T1-weighted imaging. Prescribed doses were 60 Gy and 40 Gy in 15 fractions for residual enhancing lesions and surrounding tumor-infiltrating areas, respectively. For surrounding tumor-infiltrating areas, asymmetric margins were set with reference to DTI imaging. The 1-year overall survival rate was 58.0%, and the 1-year local control rate for the residual enhancing lesions was 76.2%, while that for surrounding tumor-infiltrating areas was 39.4%. One patient (6%) developed grade 2 cerebral radiation necrosis 10 months after IMRT-SIB, but there was no grade 3 or higher adverse event. Multiparametric MRI-guided dose-escalated IMRT-SIB with DIR and DTI imaging has the potential to improve local control rates without increasing adverse events.

Intensity Modulated Radiation Therapy (IMRT) With Simultaneously Integrated Boost Shortens Treatment Time and Is Noninferior to Conventional Radiation Therapy Followed by Sequential Boost in Adjuvant Breast Cancer Treatment: Results of a Large Randomized Phase III Trial (IMRT-MC2 Trial)

In the modern era, improvements in radiation therapy techniques have paved the way for simultaneous integrated boost irradiation in adjuvant breast radiation therapy after breast conservation surgery. Nevertheless, randomized trials supporting the noninferiority of this treatment to historical standards of care approach are lacking. A prospective, multicenter, randomized phase 3 trial (NCT01322854) was performed to analyze noninferiority of conventional fractionated intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) to 3-D conformal radiation therapy with sequential boost (3-D-CRT-seqB) for breast cancer patients. Primary outcomes were local control (LC) rates at 2 and 5 years (noninferiority margin at hazard ratio [HR] of 3.5) as well as cosmetic results 6 weeks and 2 years after radiation therapy (evaluated via photo documentation calculating the relative breast retraction assessment [pBRA] score [noninferiority margin of 1.25]). A total of 502 patients were randomly assigned from 2011 to 2015. After a median follow-up of 5.1 years, the 2-year LC for the IMRT-SIB arm was noninferior to the 3-D-CRT-seqB arm (99.6% vs 99.6%, respectively; HR, 0.602; 95% CI, 0.123-2.452; P = .487). In addition, noninferiority was also shown for cosmesis after IMRT-SIB and 3-D-CRT-seqB at both 6 weeks (median pBRA, 9.1% vs 9.1%) and 2 years (median pBRA, 10.4% vs 9.8%) after radiation therapy (95% CI, -0.317 to 0.107 %; P = .332). Cosmetic assessment according to the Harvard scale by both the patient and the treating physician as well as late-toxicity evaluation with the late effects normal tissues- subjective, objective, management, analytic criteria, a score for the evaluation of long-term adverse effects in normal tissue, revealed no significant differences between treatment arms. In addition, there was no difference in overall survival rates (99.6% vs 99.6%; HR, 3.281; 95% CI: -0.748 to 22.585; P = .148) for IMRT-SIB and 3-D-CRT-seqB, respectively. To our knowledge, this is the first prospective trial reporting the noninferiority of IMRT-SIB versus 3-D-CRT-seqB with respect to cosmesis and LC at 2 years of follow-up. This treatment regimen considerably shortens adjuvant radiation therapy times without compromising clinical outcomes.

Five-year survival outcomes of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) using forward IMRT or Tomotherapy for breast cancer

Intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) reduces overall treatment duration and results in less radiotherapy (RT)-induced dermatitis. However, the use of traditional sequential approach or IMRT-SIB is still under debate since there is not enough evidence of long-term clinical outcomes. The present study investigated 216 patients who underwent breast conserving surgery (BCS) between 2010 and 2013. The median age was 51 years (range, 21–81 years). All patients received IMRT-SIB, 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Among 216 patients, 175 patients received post-operative RT with forward IMRT and 41 patients had Tomotherapy. The median follow-up was 6.4 years. Forty patients (97.6%) in the Tomotherapy arm and 147 patients (84%) in the IMRT arm developed grade 0–1 skin toxicity (P = 0.021). For the entire cohort, the 5-year and 7-year overall survival (OS) rates were 94.4% and 93.1% respectively. The 7-year distant metastasis-free survival rates were 100% vs 89.1% in the Tomotherapy and IMRT arm respectively (P = 0.028). In conclusion, Tomotherapy improved acute skin toxicity compared with forward IMRT-SIB. Chronic skin complication was 1.9%. IMRT-SIB resulted in good long-term survival.

Pain REduction with bone metastases STereotactic radiotherapy (PREST): A phase III randomized multicentric trial

BackgroundPalliative antalgic treatments represent an issue for clinical management and a challenge for scientific research. Radiotherapy (RT) plays a central role. Techniques such as stereotactic body radiotherapy (SBRT) were largely investigated in several phase 2 studies with good symptom response, becoming widely adopted. However, evidence from randomized, direct comparison of RT and SBRT is still lacking.Methods/designThe PREST trial was designed as an interventional study without medicinal treatment. It is a phase 3, open-label, multicentric trial randomized 1:1. Inclusion criteria include painful spinal bone metastases presenting with a pain level > 4 (or > 1 if being treated with an analgesic) on the Numeric Rating Scale (NRS); expected intermediate/high prognosis (greater than 6 months) according to the Mizumoto prognostic score; low spine instability neoplastic score (SINS) sores (< 7); magnetic resonance imaging (MRI) assessment of the bulky lesion. Patients will be assigned to either standard conventional radiotherapy involving 4 Gy × 5 fractions (fx) to the whole involved vertebra or SBRT by intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) involving 7 Gy × 3 fx to the whole involved vertebra + 10 Gy × 3 fx on the macroscopic lesion (gross tumor volume (GTV)). In the experimental arm, the GTV will be contoured by registration with baseline MRI.DiscussionThe primary endpoint is overall pain reduction, defined in terms of variation between baseline and 3-month evaluation; pain will be measured using the NRS. Secondary endpoints include pain control duration; retreatment rates (after a minimum interval of 1 month); local control assessed with RECIST criteria; symptom progression free survival; progression-free survival; overall survival; and quality of life (at 0, 30, and 90 days). Accrual of 330 lesions is planned. The experimental arm is expected to have an improvement in overall pain response rates of 15% with respect to the standard arm (60% according to Chow et al. (Int J Radiat Oncol Biol Phys. 82(5):1730–7, 2012)).Trial registrationClinicalTrials.gov, NCT03597984. Registered on July 2018.

A global Unified Dosimetry Index (gUDI) to evaluate simultaneous integrated boost radiotherapy plans in prostate cancer

PurposeFormulation of a global Unified Dosimetry Index (gUDI) for the evaluation of prostate simultaneous integrated boost Volumetric Modulated Arc Therapy (VMAT by RapidArc) radiotherapy plans. Methods and materialsDose coverage, conformity, homogeneity and dose gradient index could be included in the Unified Dosimetry Index (UDI). We developed a global UDI to evaluate treatment plans containing volumes irradiated with different dose prescriptions: Intensity Modulated Radiation Therapy with simultaneous integrated boost (IMRT-SIB) with 2 dose levels (36.25 Gy/5 fz for the whole prostate gland and 37.5 Gy/5 fz for Dominant Intraprostatic Lesion (DIL)).To validate gUDI scoring system, 65 prostate cancer patients were evaluated. Mean (µ) and standard deviations (σ) were calculated for all dosimetry indices and gUDI. Furthermore, gUDI µ and σ were analyzed to compare and classify treatment plans: plans can be ranked as “excellent”, “good”, “average” or “poor”. ResultsProstate Dose Gradient, Prostate Conformity and DIL Conformity indices had highlighted a major deviation from ideal scores. gUDI index classification showed most of the plans scored as “average” and “good”. ConclusiongUDI score can be a useful tool to quantify treatment plans quality also when volumes with different dose-prescription are treated.

Prospective evaluation of Intensity Modulated Radiation Therapy with Simultaneous Integrated Boost (IMRT-SIB) in head and neck squamous cell carcinoma in patients not suitable for chemo-radiotherapy

BackgroundWith conformal radiotherapy techniques, acute and late toxicities can be reduced because of better dose conformity and reduced doses to normal tissue. With Intensity Modulated Radiation Therapy (IMRT) further dose escalation is possible and one of the methods is IMRT with simultaneous integrated boost (IMRT-SIB). AimTo evaluate feasibility, toxicity patterns and loco-regional control rates of IMRT-SIB technique in head and neck cancer patients who are not suitable candidates for concurrent chemoradiation. Study designProspective study of 30 patients treated with IMRT-SIB technique and evaluation of clinical results. Method and materials30 patients received definitive treatment using IMRT-SIB without concurrent chemotherapy. Patients were monitored during and after treatment for toxicity using the Radiation Therapy Oncology group (RTOG) criteria. Analysis of acute and late toxicity and early efficacy is presented. ResultsThe median treatment duration was 42days (range 41–43days). Overall, maximum acute Grade 3 toxicity of mucositis, skin, pharynx/esophageal toxicity and laryngeal were 56.66%, 30%, 26.67%, and 6.67% respectively at treatment completion. None of the patients had Grade 4 acute toxicity. No haematological toxicity was seen. Overall, grade 2 late toxicities were 7% (subcutaneous toxicity) and 13.3% (Xerostomia). Loco regional control rate at a median follow up of 13months was 86%. ConclusionIMRT-SIB is a safe and acceptable treatment option for patients of head and neck squamous cell carcinoma unsuitable for definitive chemo-radiotherapy.

Maximum surgical resection and adjuvant intensity-modulated radiotherapy with simultaneous integrated boost for skull base chordoma.

Local recurrence is common after surgical resection of clivus chordoma. We report the results of maximum surgical resection followed by intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB). We reviewed 14 consecutive clivus chordoma cases undergoing postoperative IMRT-SIB using the institutional protocol between 2005 and 2013. Total and near-total resections were achieved in 11 patients (78.6%), partial in 2 patients (14.3%), and 1 patient (7.1%) received RT for recurrent tumor after total resection. Gross residual or the high-risk area defined the planning target volume (PTV)1; PTV2 was the postoperative tumor bed plus a 3-5-mm margin, and PTV3 was PTV2 plus a 5-10mm margin. A moderate hypofractionation schedule was used: doses to PTV1, PTV2 and PTV3 were 3.9Gy, 3.15Gy and 2.8Gy through 15 fractions for the first two patients, and the rest received 2.5Gy, 2.2Gy and 1.8Gy through 25 fractions. The biologically equivalent dose in 2-Gy fractions (EQD2) was 65-68Gy for PTV1, 52-56Gy for PTV2, and 44.3-44.8Gy for PTV3. Median follow-up was 41months. Eight patients were free of disease for median 42.5months (range 23-91 months), four patients had stable disease for median 60.5months (range 39-113 months), and 1 patient showed partial response for 38months after RT. Local progression was seen in one patient who received EQD2 67.8Gy after partial resection. Estimated 5-year progression-free and overall survival rates were 92.9%. Surgery improved the neurologic deficit in six patients, and IMRT-SIB was well tolerated without lasting toxicity. Our experience suggests that maximum resection and high-dose IMRT-SIB can achieve local control without significant morbidities.

Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma.

AimIn recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF) have been involved in the treatment of nasopharyngeal carcinoma (NPC). However, the potential clinical effects and toxicities are still controversial.MethodsHere, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS), 5-year progression-free survival (PFS), 5-year locoregional recurrence-free survival (LRFS), and relevant toxicities were analyzed.ResultsIn the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months). The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568). In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773) and 5-year LRFS (88.1% vs 90.8%, P=0.903). Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland) in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05).ConclusionBoth IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.

Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma.

To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB). We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIB-based neoadjuvant chemoradiation protocol. During the concurrent chemoradiation therapy, radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume, with a regimen at the discretion of the treating medical oncologist. This was followed by surgical tumor resection. We analyzed pathological completion response (pCR) rates its relationship with overall survival and event-free survival. Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis. Among the IMRT-SIB-treated patients, the toxicity appeared mild, the most common side effects were grade 1-3 esophagitis (46%) and pneumonitis (11.7%). There were no cardiac events. The Ro resection rate was 94% (n = 16), the pCR rate was 47% (n = 8), and the postoperative morbidity was zero. There was one mediastinal failure found, one patient had local failure at the anastomosis site, and the majority of failures were distant in the lung or bone. The 3-year disease-free survival and overall survival rates were 41% (n = 7) and 53% (n = 9), respectively. The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

Intensity modulated radiotherapy with simultaneous integrated boost vs. conventional radiotherapy with sequential boost for breast cancer – A preliminary result

PurposeThis study was aimed to assess the acute dermatological adverse effect from two distinct RT techniques for breast cancer patients. We compared intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and conventional radiotherapy followed by sequential boost (CRT-SB). MethodsThe study population was composed of 126 consecutive female breast cancer patients treated with breast conserving surgery. Sixty-six patients received IMRT-SIB to 2 dose levels simultaneously. They received 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Sixty patients in the CRT-SB group received 50 Gy in 25 fractions to the whole breast followed by a boost irradiation to tumor bed in 5–7 fractions to a total dose of 60–64 Gy. Acute skin toxicities were documented in agreement with the Common Terminology Criteria for Adverse Events version 3 (CTCAE v.3.0). ResultsNinety-eight patients had grade 1 radiation dermatitis while 14 patients had grade 2. Among those with grade 2, there were 3 patients in IMRT-SIB group (4.5%) while 11 in CRT-SB group (18.3%). (P = 0.048) There was no patient with higher than grade 2 toxicity. Three year local control was 99.2%, 3-year disease free survival was 97.5% and 3-year overall survival was 99.2%. ConclusionsA significant reduction in the severity of acute radiation dermatitis from IMRT-SIB comparing with CRT-SB is demonstrated.

Intensity-modulated radiotherapy with simultaneous integrated boost for locoregionally advanced nasopharyngeal carcinoma

ObjectiveTo compare the treatment outcomes of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) alone to concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma (NPC).MethodsFrom November 2001 to December 2009, 333 patients with pathologically diagnosed, locoregionally advanced NPC were treated by IMRT-SIB with or without weekly cisplatin concurrent chemotherapy at our institute. Among them, 62 patients received neo- or adjuvant chemotherapy or molecular target drugs were excluded from this analysis. There were 129 patients received IMRT-SIB alone, and 142 patients received IMRT-SIB with weekly cisplatin 30 mg/m2 for 7 weeks. The radiotherapy protocol was identical for each group.ResultsThere were no significant differences in survival between CCRT and IMRT-SIB group in terms of gender, T/N classifications and concurrent chemoradiotherapy. The 5-year local control (LC), overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) for the entire group were 87.0%, 79.4%, 69.7 and 83.3%, respectively. The LC, OS, DFS and DMFS for CCRT and IMRT-SIB alone groups were 80.6% vs. 90.8% (P = 0.10), 71.7% vs. 83.2% (P = 0.201), 63.9% vs. 74.6% (P = 0.07), and 79.6% vs. 86.0% (P = 0.27), respectively.ConclusionCompared to CCRT, IMRT-SIB alone had demonstrated similar disease LC, OS, DFS and DMFS in locoregionally advanced NPC. Careful radiation target volume design and simultaneous integrated boost may play a role that overrides the benefit from concurrent chemotherapy. Further investigation with randomized study is necessary to determine whether IMRT-SIB alone can achieve similar outcomes of concurrent chemoradiotherapy.

Impact of Gastric Filling on Radiation Dose Delivered to Gastroesophageal Junction Tumors

This study examined the impact of gastric filling variation on target coverage of gastroesophageal junction (GEJ) tumors in three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), or IMRT with simultaneous integrated boost (IMRT-SIB) plans. Eight patients previously receiving radiation therapy for esophageal cancer had computed tomography (CT) datasets acquired with full stomach (FS) and empty stomach (ES). We generated treatment plans for 3DCRT, IMRT, or IMRT-SIB for each patient on the ES-CT and on the FS-CT datasets. The 3DCRT and IMRT plans were planned to 50.4 Gy to the clinical target volume (CTV), and the same for IMRT-SIB plus 63.0 Gy to the gross tumor volume (GTV). Target coverage was evaluated using dose-volume histogram data for patient treatments simulated with ES-CT sets, assuming treatment on an FS for the entire course, and vice versa. FS volumes were a mean of 3.3 (range, 1.7-7.5) times greater than ES volumes. The volume of the GTV receiving >or=50.4 Gy (V(50.4Gy)) was 100% in all situations. The planning GTV V(63Gy) became suboptimal when gastric filling varied, regardless of whether simulation was done on the ES-CT or the FS-CT set. Stomach filling has a negligible impact on prescribed dose delivered to the GEJ GTV, using either 3DCRT or IMRT planning. Thus, local relapses are not likely to be related to variations in gastric filling. Dose escalation for GEJ tumors with IMRT-SIB may require gastric filling monitoring.