Integrated Boost Research Articles

Oligometastases Treated With an Elective Simultaneous Integrated Boost Have Reduced Marginal Recurrence Rates

<h3>Purpose/Objective(s)</h3> Radiation is increasingly used to treat oligometastatic patients (OM). Following metastasis directed radiation therapy, progression in nearby nodal basins or bones is common. We previously reported clinical outcomes of OM treated with an elective simultaneous integrated boost (SIB) technique delivering higher doses to known metastases and reduced doses to adjacent bones/nodal basins. Here we compare outcomes of OM receiving radiation to metastases alone (MA) versus those treated via an SIB. We hypothesized that use of SIB would maintain treated metastasis control (TMC) while reducing MR. <h3>Materials/Methods</h3> OM patients with ≤5 active metastases treated with either SIB or MA at our IRB approved sites from 2013-2018 were analyzed for toxicities, pain control, and recurrence patterns. TMC was defined as absence of progression in high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside elective PTV, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as any recurrence outside of the treatment PTVs not meeting other criteria. Outcome rates were estimated using the Kaplan-Meier method. Patients treated with the two techniques were compared using the log rank test. <h3>Results</h3> 101 patients were treated to 90 SIB (58% nodal and 42% osseous) and 46 MA (22% nodal and 78% osseous) sites. The most common primary tumors were prostate (37%), lung (15%), and breast (7%). Median follow up among surviving patients was 24.6 months (range 1.4-71.0). Of the MA treated patients, doses ranged from 18 Gy in 1 fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No patients in either cohort experienced acute grade ≥3 toxicity. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis n = 1, vertebral body compression n = 2) and no MA patients. There was similar crude pain relief between cohorts: 82% with MA (9/11 patients reporting improved pain) and 86% with SIB (19/22). Crude MR were more frequent in the MA group 13% (n = 6) compared to SIB group 2% (n = 2). MR-free survival at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (<i>P</i> = 0.07). Crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences found in DR-free survival (<i>P</i> = 0.24) or Disease-free survival (<i>P</i> = 0.4) and Overall survival (<i>P</i> = 0.26) between MA and SIB cohorts. <h3>Conclusion</h3> Both SIB and MA irradiation of OM achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for OM treated with SIB. Although more late grade 3 toxicities were seen in the SIB cohort, these were mechanistically related to the high dose PTV and not the elective volume, with differences in treated metastasis location/characteristics. Further investigation of this technique with prospective trials is warranted.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: Late Toxicity and Biochemical Recurrence Results From a Prospective Trial

<h3>Purpose/Objective(s)</h3> Stereotactic Body Radiation Therapy (SBRT) is increasingly utilized as a definitive treatment option for patients with prostate adenocarcinoma, especially in the low or intermediate risk setting. The aim of this study is to assess the late toxicity and biochemical recurrence rates of a single institution prospective clinical trial evaluating prostate SBRT with simultaneous integrated boost (SIB) targeting focal lesions as defined by magnetic resonance imaging (MRI). <h3>Materials/Methods</h3> Patients were eligible if they had biopsy-proven low or intermediate risk prostate adenocarcinoma with initial prostate specific antigen (PSA) values ≤20 ng/mL, clinical stage from T1c to T2c, and Gleason score ≤7. Patients also had to have one or more focal lesions on MRI and an MRI-defined total prostate volume of < 120 cm³. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after three months from the completion of SBRT and graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Biochemical recurrence was defined by the Phoenix definition of PSA increase of 2 ng/mL above the nadir. <h3>Results</h3> A total of 26 patients were enrolled, and all enrolled patients underwent planned SBRT. Six patients (23.1%) had low risk disease and twenty patients had intermediate risk disease (76.9%). Eight patients (30.8%) received androgen deprivation therapy. Median follow up was 40.5 months (range 12-64 months). No biochemical failures have yet been observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy; two of these three patients experienced hematuria requiring cystoscopy and one patient experienced dysuria requiring cystoscopy. Six patients (23.1%) had late grade 2 GU toxicity requiring medications such as tamsulosin or oxybutynin. Two patients (7.7%) had late grade 2 gastrointestinal (GI) toxicity; both patients experienced hematochezia requiring colonoscopy and were found to have proctitis requiring steroids per rectum. There was no grade 3 or higher toxicity events observed. <h3>Conclusion</h3> The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions is not associated with undue late GI or GU toxicity. Thus far, this regimen has excellent biochemical control. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

A Prospective Phase II Clinical Study of Simultaneous Integrated Boost Radiotherapy on Stage III Local-advanced Non-Small Cell Lung Cancer Patients

In consideration of the results of the RTOG0617 study, researchers began to adopt a prudent policy to high-dose radiotherapy. Based on the assume that radiation dose escalation to the primary tumor can improve local control and therefore producing survival benefits under the condition of limiting the dose to the organ at risk (OAR), we launched the study to evaluate the effect of simultaneous Integrated boost (SIB) radiotherapy implemented on the stage III local-advanced non-small cell lung cancer (LA-NSCLC) patients.42 Patients with stage III LA-NSCLC who were eligible for definite concurrent chemoradiotherapy were prospectively given the radiation regimen of single dose of 2.0Gy for PTV, 2.2Gy for CTV, and 2.4 -2.8Gy for GTV with 25 fractions. Other stage III LA-NSCLC patients retrospectively collected with routinely radiotherapy were matched through PSM. 2 Cycles of platinum based concurrent chemotherapy were carried on patients in both groups. The primary endpoints were progression-free survival (PFS), toxic effects and dose for normal tissues, with the secondary end point of overall survival (OS). The Kaplan-Meier method was used to evaluate PFS and OS, and the Mann-Whitney U test for toxic effects and the dose for normal tissues.The median PFS time was 20.6 vs 9.0 months (P = 0.01), and the median OS was 40.0 vs 24.5 months (P = 0.02) in the SIB group and the control group respectively, all were obviously longer in the SIB group. No significant differences of radiation-related pneumonitis (P = 0.95) and myelosuppression (P = 0.40) have been observed between the two groups, as well as nausea, vomiting, esophagitis and dyspnea. The dose and the radiation-effected volume to the surrounding normal tissues also did not show the tendency of increasement in the SIB group.The results of our research has revealed that the dose escalation did improve the PFS and OS while not increased the dose to the surrounding normal tissues and the occurrence of toxic effects. Simultaneous integrated boost radiotherapy to the primary tumor might be a safe and feasible regimen to improve survival benefit for the stage III LA-NSCLC patients eligible for definite concurrent chemoradiotherapy in the future.

A Pilot Study of Hypofractionated Simultaneous Integrated Boost Radiotherapy in Stage 0-IIIB Breast Cancer Patients

In the UK START and Canadian hypofractionated whole breast radiotherapy (RT) trials, few patients were Black, received prior chemotherapy, or had large breast size, all factors associated with RT-induced breast toxicity. The purpose of this prospective trial was to assess the safety and efficacy of delivering 15 fractions of hypofractionated simultaneous integrated boost (SIB) RT to patients under-represented on trials of hypofractionated breast RT and who have characteristics which increase their risk for local recurrence and cutaneous toxicity from breast RT.We conducted a prospective, single-arm pilot study to evaluate a once daily 15 fraction SIB RT regimen of 39.9 Gy in 2.66 Gy fractions to the breast/chest wall with or without regional nodal irradiation (RNI) and SIB of 8.1 Gy in 0.54 Gy fractions. Women with Stage 0-IIIB breast cancer who had one or more of the following characteristics were approached for enrollment: 1) prior chemotherapy for breast cancer; 2) > 25 cm breast/chest wall separation; 3) non-White race; 4) ≤ 50 years old; or 5) requiring RNI. Primary endpoint was Grade 3 cutaneous toxicity rate by CTCAE v.5. Among patients who received RNI (n = 30), rates of Grade 3 brachial plexopathy by RTOG criteria and 20% or greater increase in arm lymphedema, were additional primary endpoints. Patients were assessed prior to RT, last day of RT, and 3 weeks, 9 weeks and 1 year post RT. Local regional recurrence free survival (LRFS) was a secondary endpoint.Among 74 participants, 57% received prior chemotherapy, 19% had breast/chest wall separation > 25cm, 39% were Black, 36% were ≤ 50 years old, and 41% were prescribed RNI. Median body mass index was 30.0 (range 17.3 - 54.9). Ten patients received post mastectomy RT. One patient developed Grade 3 radiation dermatitis 3 weeks post RT. No other Grade 3 or higher cutaneous toxicities were observed up to 1 year post RT. One patient developed a grade 3 axillary infection 3 weeks post RT, which resolved after intravenous antibiotics. No patients who received RNI developed grade 3 brachial plexopathy or a 20% increase in the ipsilateral arm volume during the study period. With a median follow up of 60 months (range 12-113 months), one in-breast recurrence with simultaneous distant metastases occurred. Two additional patients developed distant metastases alone. The 5-year LRFS and overall survival rates were 98.6% and 98.5%, respectively.Our results indicate that SIB radiation therapy is well-tolerated with acceptable cutaneous toxicity rates up to 1 year post RT even among patients who are at high risk for RT-induced breast side effects. The high rates of local control and overall survival following SIB treatment are promising and support condensed courses of RT in patients who would typically receive a sequential boost due to higher risk for local recurrence.

Prostate-Centric vs. Bony-Centric Registration in the Definitive Treatment of Node-Positive Prostate Cancer With Simultaneous Integrated Boost: A Dosimetric Comparison

<h3>Purpose/Objective(s)</h3> To determine the impact of daily shifts based on rigid registration to intraprostatic markers (IPMs) on coverage of boost doses delivered to gross nodal disease for prostate cancer. <h3>Materials/Methods</h3> Seventy-five cone-beam CTs (CBCTs) from 15 patients treated with definitive radiation for clinically node-positive prostate cancer underwent fiducial-based and pelvic bony-based registration to the initial planning scans. Gross tumor volumes of nodal boost targets were contoured directly on each CBCT registration. The nodal displacement (3-dimensional translation from the node centroid on planning CT to node centroid on registered CBCT) and dose coverage (minimum dose [Dmin], mean dose [Dmean], dose delivered to 95% of the GTV [D95]) were calculated for each registration on all nodal targets. All doses for each node were normalized to its prescription dose (dose covering 95% of a 3 mm PTV expansion). <h3>Results</h3> Forty-one gross nodal targets were analyzed. Most boosted nodes (80.5%, 33/41) were treated with volumetric-arc radiation therapy (VMAT), while 19.5% (8/41) underwent stereotactic body radiation therapy (SBRT). Dmin, Dmean, and D95 were all significantly lower with fiducial-based registration compared to bony-based registration (<b>P</b> < 0.0001). Nodal displacement was significantly higher for fiducial-based registrations (<b>P</b> < 0.0001). The 3-dimensional translation between the fiducial-based and bony-based registrations (bony-to-fiducial vector) was the most significant predictor of nodal displacement (<b>P</b> < 0.0001). On fiducial-based registrations, a 3-5 mm gross nodal PTV margin is sufficient in most directions; however, superior and posterior margins of 8-9 mm are required as a result of asymmetric prostatic motion. <h3>Conclusion</h3> Large and anisotropic PTV margins are likely needed to adequately dose gross nodal targets when patient setup is based on rigid registration to IPMs. Alternative approaches such as adaptive replanning may be required to overcome these limitations.

Ten Year Results of Extensive Nodal Radiotherapy and Moderately Hypofractionated Simultaneous Integrated Boost in Unfavorable Intermediate-, High-, and Very High-Risk Prostate Cancer.

Simple SummarySeveral phase III randomized trials of moderate hypofractionation, including a higher proportion of high-risk prostate cancer patients treated only to the prostate, failed to demonstrate the superiority of hypofractionated regimens. There is only one randomized phase III trial, of moderately hypofractionated high-dose radiotherapy to the prostate-only versus pelvic irradiation and prostate boost, with a sufficiently long follow-up. It demonstrated better biochemical and disease-free survival when lymph nodal radiotherapy was added. Here we present the 10-year results of our experience based on an Institutional protocol adopted after a phase I–II study, on patients with unfavorable intermediate- (UIR), high- (HR), and very high-risk (VHR) prostate cancer (PCa) treated with pelvic lymph nodal irradiation (WPRT) and moderately hypofractionated high-dose (HD) simultaneous integrated boost (SIB) to the prostate. Prognostic factors for relapse, as well as acute and late gastro-intestinal (GI) and genito-urinary (GU) toxicity were also analyzed.Aims: To report 10-year outcomes of WPRT and HD moderately hypofractionated SIB to the prostate in UIR, HR, and VHR PCa. Methods: From 11/2005 to 12/2015, 224 UIR, HR, and VHR PCa patients underwent WPRT at 51.8 Gy/28 fractions and SIB at 74.2 Gy (EQD2 88 Gy) to the prostate. Androgen deprivation therapy (ADT) was prescribed in up to 86.2% of patients. Results: Median follow-up was 96.3 months (IQR: 71–124.7). Median age was 75 years (IQR: 71.3–78.1). At last follow up, G3 GI–GU toxicity was 3.1% and 8%, respectively. Ten-year biochemical relapse-free survival (bRFS) was 79.8% (95% CI: 72.3–88.1%), disease-free survival (DFS) 87.8% (95% CI: 81.7–94.3%), overall survival (OS) 65.7% (95% CI: 58.2–74.1%), and prostate cancer-specific survival (PCSS) 94.9% (95% CI: 91.0–99.0%). Only two patients presented local relapse. At univariate analysis, VHR vs. UIR was found to be a significant risk factor for biochemical relapse (HR: 2.8, 95% CI: 1.17–6.67, p = 0.021). After model selection, only Gleason Score ≥ 8 emerged as a significant factor for biochemical relapse (HR = 2.3, 95% CI: 1.12–4.9, p = 0.023). Previous TURP (HR = 3.5, 95% CI: 1.62–7.54, p = 0.001) and acute toxicity ≥ G2 (HR = 3.1, 95% CI = 1.45–6.52, p = 0.003) were significant risk factors for GU toxicity ≥ G3. Hypertension was a significant factor for GI toxicity ≥ G3 (HR = 3.63, 95% CI: 1.06–12.46, p = 0.041). ADT (HR = 0.31, 95% CI: 0.12–0.8, p = 0.015) and iPsa (HR = 0.37, 95% CI: 0.16–0.83, p = 0.0164) played a protective role. Conclusions: WPRT and HD SIB to the prostate combined with long-term ADT, in HR PCa, determine good outcomes with acceptable toxicity.

PO-1272 Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost in Carcinoma of the Anal Canal

PO-1272 Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost in Carcinoma of the Anal Canal

Dosimetric evaluation of IMRT (SS / SW) and VMAT treatment plans for nasopharyngeal cancer

Introduction: Radiotherapy of the sphere ORL is still difficult by the presence of complex geometries and very sensitive organs around the target volume.This weapon has benefited from the advances of the VMAT (Volumetric Modulated Arc Therapy) technique, introduced in 2009, it combines the advantages of dynamic arc therapy techniques with the advantages of conformational radiotherapy techniques with intensity modulation (RCMI) by stationary beams.Materials and Methods: The treatment plans of the 4 patients were compared and treated with SS, SW, and VMAT (6MV X-ray beam). The target volumes were three: PTV 70, PTV 63, and PTV56. The organs at risk delineated were the spinal cord, the brainstem, the parotid gland .The dose was delivered once a day, five days a week and in 35 sessions in Integrated Boost (Simultaneaous Integrated Boost (SIB)), aiming to deliver the prescribed dose to the tumor volume while respecting the dose constraints in the organs at risk and minimizing their degree of toxicity.Results: Similar results were found for target volume coverage (Dmax). The SS technique allowed better parotid sparing, which explains its contribution to limiting late complications such as xerostomia. The VMAT technique allows better protection of the brainstem by reducing about 6 Gy, for the spinal cord the doses received were almost equal. Finally, there is no statistically significant difference between the different techniques.Conclusion: All these results conform the conformational capacities of these innovative techniques from a dosimetric and above all clinical point of view. Their ability to cover the target volumes while largely respecting the constraints on organs at risk.

Analysis and Control of Current-Fed Integrated Dual-DC Boost Converter Topology

This article introduces a dual-input single-output dc–dc power electronic converter topology to interface two independent sources into a common output. The proposed converter is denoted as integrated dual-dc boost converter (IDDBC), and this topology provides step-up conversions for both inputs using three controllable switches. Due to its architecture, IDDBC can be adapted to provide uninterrupted power (realizing a dispatchable system) even if any one of the two input sources are unavailable or has significant output power variation. The steady-state analysis, modeling, and design of the converter are presented, and a pulsewidth-modulation control scheme is proposed. The closed-loop control system for the converter consists of voltage-mode control for output and current-mode control for one-source input current. The behavior of converter operation is validated through experimentation on a digital-signal-processor-based laboratory prototype.

IMAT-IGRT Treatment with Simultaneous Integrated Boost as Dose Escalation for Patients with Cervical Cancer: A Single Institution, Prospective Pilot Study

Purpose: The aim of this study was to introduce the simultaneous integrated boost (SIB) technique to assess the safety of replacement of the brachytherapy (BT) boost for ineligible patients with cervical cancer receiving radiochemotherapy (RCT). Methods: Fourteen patients were enrolled between 2015 and 2018. SIB was delivered using RapidArc technique at doses of 2.4 Gy per fraction during pelvic irradiation with 50.4/1.8 Gy in seven patients (to a total dose of 67.2 Gy) with limited volume disease. In 7 patients with a more advanced disease stage (>5 cm tumor, parametric invasion both sides), parametric boost therapy was added to the pelvic radiotherapy to a total dose of the macroscopic tumor of 79.2 Gy. All patients received simultaneous cisplatin-based chemotherapy for 5 cycles with a dosage of 40 mg/m2. We examined acute toxicity (CTCAE v4.1) and quality of life (EORTC QLQ30 and CX24). The tumor regression rate was evaluated with RECIST 1.1 after the first 3- to 4-months follow-up Magnetic Resonance Imaging (MRI) scan. We calculated the percentage of tumor regression rate and the local control during the follow-up period and evaluated the survival data. Results: Our patient data are presented at a median follow-up time of 24.5 months. During the treatment period, no grade 3 to 4 toxicity was observed. During the follow-up period, no late-onset toxicity was observed. The tumor regression rate at the first MRI scan was 95.31% on average. Disease free survival (DFS) during the median follow-up of 24 months was 98.6%. Conclusion: In patients with cervical cancer, the SIB technique is amenable as part of definitive RCT. Dose escalation with the SIB technique can be safely administered to cervical cancer patients during definitive RCT if BT is not feasible. However, further randomized clinical studies are needed to validate the method, so routine use of it cannot be recommended yet.

The patient-reported outcome measures in oropharyngeal, laryngeal and hypopharyngeal cancer patients treated with Volumetric Modulated Arc based simultaneous integrated boost radiotherapy.

To assess the change in the quality of life (QOL) in head and neck cancer patients treated with Simultaneous Integrated Boost (SIB) by Volumetric Modulated Arc Therapy (VMAT) technique. Thirty patients with localised head and neck cancers (Stage II- IVa) were treated with VMAT and SIB technique. The three-dose levels prescribed were 68.2 Gy at 2.2 Gy/fraction, 62 Gy at 2 Gy/fraction and 55.8 Gy at 1.8 Gy/fraction to the high, intermediate and low-risk volumes respectively. Concurrent chemotherapy with cisplatin 100 mg/m2 was administered once in three weeks. Acute toxicities were evaluated and scored according to the RTOG grading system. Quality of life (QOL) was assessed using European Organization of Research and Treatment of Cancer (EORTC) QLQC30 and HN35 questionnaires at baseline and in three instances (immediately, one month and three months after the radiotherapy). Out of the total 30, 80% patients had a complete response (CR) at the median follow up of 12 months, while three patients died because of progression, and the remaining 3 had stable disease. All planning objectives were achieved for organs at risk and planning target volume(PTV). There was a statiscally significant(p value < 0.001) reduction in global quality of life scores at the end of treatment when compared to baseline scores, but by three months, there was the return in the QOL scores in most scales similar to the baseline value. VMAT based Simultaneous boost radiotherapy is a feasible and safe strategy in terms of toxicityprofile with an acceptable transient change in the quality of life and allows a faster return to baseline quality of life.

Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2).

BackgroundGlioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM.MethodsA Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV1 was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV2 was the CTV1 plus 20-mm margin. Only PTV1 dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV2 dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale).ResultsThirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded.ConclusionsAccording to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.

Feasibility and Oncological Outcome of Preoperative Chemoradiation With IMRT Dose Intensification for Locally Advanced Esophageal and Gastroesophageal Cancer.

PurposeTo explore the feasibility and efficacy of a dose intensification with Intensity Modulated Radiation Therapy and Simultaneous Integrated Boost (IMRT-SIB) in locally advanced esophageal and gastroesophageal cancer (GEJ).Methods and MaterialsWe retrospectively analyzed a series of 69 patients with esophageal or GEJ cancer treated at our Institute, between 2016 and 2019, with preoperative IMRT and SIB up to 52.5–54 Gy in 25 fractions in 5 weeks and concurrent carboplatin (AUC2) and paclitaxel (50 mg/m2), as in the CROSS regimen.ResultsAll patients completed the planned IMRT–SIB program with a median of four (range 1–5) cycles of concurrent paclitaxel/carboplatin. Compliance to IMRT–SIB was 93%, whereas 54% of patients received four to five cycles and 87% at least three cycles of concurrent carboplatin/paclitaxel. Grade 3 toxicity was reported in 19% of patients. Complete clinical response (cCR) was achieved in 48%, and 13% had disease progression after chemoradiation (CRT). Overall, 49% of patients underwent surgery; reasons for non-operation included cCR in cervical tumor location (10%) or cCR and patient decision (13%). A pathologic complete response (pCR) was achieved in 44% of resected patients. Postoperative complications and mortality rates were 21 and 6%, respectively. At a median follow-up of 12 months (6–25), 2-year overall and progression-free (PFS) survival rates were 81 and 54%, respectively. No difference in PFS by histologic type in operated patients was reported. Non-operated cCR patients had higher PFS, including cervical locations and selected cCR patients who decided for non-operation (75 vs 30%, p < 0.01).ConclusionThe study reported favorable results in safety and feasibility of the IMRT–SIB dose intensification in our preoperative CRT program. The toxicity was acceptable, allowing a high compliance to intensified radiation doses with dose reduction of concurrent paclitaxel/carboplatin in some patients. The high rate of cCR and pCR suggested this intensified program is effective in the preoperative CRT and, for selected responsive patients, in the non-operative approach to esophageal and GEJ cancer. The 2-year survival rates were promising. A prospective study is being planned to confirm these observations.

Deep Learning–Based Fluence Map Prediction for Pancreas Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost

PurposeTreatment planning for pancreas stereotactic body radiation therapy (SBRT) is a challenging task, especially with simultaneous integrated boost treatment approaches. We propose a deep learning (DL) framework to accurately predict fluence maps from patient anatomy and directly generate intensity modulated radiation therapy plans. Methods and MaterialsThe framework employs 2 convolutional neural networks (CNNs) to sequentially generate beam dose prediction and fluence map prediction, creating a deliverable 9-beam intensity modulated radiation therapy plan. Within the beam dose prediction CNN, axial slices of combined structure contour masks are used to predict 3-dimensional (3D) beam doses for each beam. Each 3D beam dose is projected along its beam’s-eye-view to form a 2D beam dose map, which is subsequently used by the fluence map prediction CNN to predict its fluence map. Finally, the 9 predicted fluence maps are imported into the treatment planning system to finalize the plan by leaf sequencing and dose calculation. One hundred patients receiving pancreas SBRT were retrospectively collected for this study. Benchmark plans with unified simultaneous integrated boost prescription (25/33 Gy) were manually optimized for each case. The data set was split into 80/20 cases for training and testing. We evaluated the proposed DL framework by assessing both the fluence maps and the final predicted plans. Further, clinical acceptability of the plans was evaluated by a physician specializing in gastrointestinal cancer. ResultsThe DL-based planning was, on average, completed in under 2 minutes. In testing, the predicted plans achieved similar dose distribution compared with the benchmark plans (-1.5% deviation for planning target volume 33 V33Gy), with slightly higher planning target volume maximum (+1.03 Gy) and organ at risk maximum (+0.95 Gy) doses. After renormalization, the physician rated 19 cases clinically acceptable and 1 case requiring minor improvement. ConclusionsThe DL framework can effectively plan pancreas SBRT cases within 2 minutes. The predicted plans are clinically deliverable, with plan quality approaching that of manual planning.

Radiation-induced Mucositis in Patients with Oropharyngeal Cancer Treated with Moderate Acceleration of Intensity-modulated Radiation Therapy and Simultaneous Integrated Boost Concomitant with Weekly Cisplatin

BACKGROUND: Radiation-induced mucositis is one of the limiting factors during radiotherapy, disturbing the quality of life and in some cases leading to discontinuation of therapy. Intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) represents advanced form of radiotherapy technique in treatment of oropharyngeal carcinoma enabling precision cancer targeting with reducing dose to healthy normal tissues.&#x0D; AIM: The aim of this study was to present maximum grade and duration of a maximum grade of radiation-induced acute mucositis, influence of total volume of oral mucosa, and volumes of oral mucosa which are encompassed by radiation volume of 54 Gy and 66 Gy on the expression of grade of acute mucositis and influence of primary origin of tumor on encompassing with radiation volumes in patients treated with moderate acceleration of IMRT-SIB concomitant weekly cycle of chemotherapy with cisplatin.&#x0D; MATERIALS AND METHODS: Planned research included 30 patients with oropharyngeal cancer who received their treatment at the University Clinic of Radiotherapy and Oncology in Skopje with moderate acceleration of IMRT-SIB and weekly concomitant cisplatin. Assessment of radiation-induced acute mucositis was performed according to the acute radiation morbidity scoring criteria of the Radiation Therapy Oncology Group.&#x0D; RESULTS: Maximum grade of acute reaction was confluent mucositis with strong pain and was manifested in 27 patients (90%) with maximum time of duration of 28 days (range 7–28) and median duration of 18 days (range 7–28). Patients, in whom the primary origin of tumor was base of the tongue, a statistically significant difference (p = 0.04) was found for volume of oral mucosa encompassed with PTV66, compared to other localizations of primary oropharyngeal origin. Statistically non-significant difference was found between volume of total oral mucosa and volumes of oral mucosa which are encompassed with radiation volume of 54 Gy and 66 Gy and expression of grade of acute mucositis in the 5th and 6th weeks of radiotherapy.&#x0D; CONCLUSION: According to these results, recommendations are delineation of oral mucosa as critical structure and implementation of IMRT-SIB to achieve reduction of grade of acute mucositis.

Body Irradiation Using Tomotherapy Helical &amp; Direct Technique Using Radixact for Young and Paediatric Patients

Background: We have treated 14 patients of total body irradiation (TBI) in Helical Tomotherapy, out of which 9 are males and 5 are females, age is 5 years to 33 years with acute lymphoblastic leukemia (ALL) remission or acute myeloic leukemia (AML). Total Body Irradiation is an important procedure in the conditioning for Bone Marrow and stem cell transplantation. We present here our treatment technique, treatment planning, delivery and dose verification. Standard Total prescribed dose of target volume 12 Gy in 6 fractions twice daily over 3 days to the whole body with Simultaneous Integrated Boost of 14 Gy/6# to brain. Dose volume constraint for the planning treatment volume (PTV) 95% of prescribed dose is getting by 95% of the volume. Material and Methods: We immobilized the whole body of the patients from Vac-loc and thermoplastic mask for head. We take two computerized tomography (CT) scan for treatment Planning. Result: Average dose D95 to the planning treatment volume was 11.7 Gy corresponding to a mean coverage of the planning treatment volume of 95%. Average dose (D-mean) for the lungs was not exceeding 9 Gy. Conclusions: Total Body Irradiation using helical Tomotherapy is achievable and well tolerated. Each dose distribution is homogeneous and reduce dose to at risk organ.

Hypofractionated Simultaneous Integrated Boost Radiotherapy Versus Conventional Fractionation Radiotherapy of Early Breast Cancer After Breast-Conserving Surgery: Clinical Observation and Analysis.

Purpose: The objective of this retrospective study is to evaluate the efficacy and safety of hypofractionated simultaneous integrated boost radiotherapy for early breast cancer patients undergoing breast-conserving surgery. Methods: A total of 185 women with early breast cancer undergoing breast-conserving surgery were retrospectively divided into hypofractionated simultaneous integrated boost group and conventional fractionation group. Hypofractionated simultaneous integrated boost included 104 patients and the dose of whole-breast radiation reached 42.56 Gy in 16 fractions and simultaneously tumor bed boost to 48 Gy in 16 fractions, which course of radiotherapy was 22 days. The 81 patients of the conventional fractionation group received whole breast radiation to 50 Gy in 25 fractions and followed by tumor bed boost to 10 Gy in 5 fractions, which course of radiotherapy was 40 days. Clinical information including patients’ characteristics, skin toxicity, myelosuppression, radiation pneumonia, and cosmetic effects was recorded to analyze the influence of age, chemotherapy, position, and breast volume on the results of radiotherapy. Results: Hypofractionated simultaneous integrated boost group had no case of recurrence after a median follow-up of 25.6 months (9-47 months)) as compared with 2 after a median follow-up of 33.4 months (25-45 months) in the conventional fractionation group. The 2 groups had similar results in skin toxicity, cosmetic outcomes, and radiation pneumonia. In terms of myelosuppression, grade 1, grade 2, and grade 3 of myelosuppression in the hypofractionated simultaneous integrated boost group accounted for 16.7%, 12.3%, and 3.5% as compared with 30.0%, 21.1%, and 12.3% of the conventional fractionation group, respectively (P = .000). Conclusions: HF-SIB RT is a considerable option in patients after breast-conserving surgery with a lower degree of myelosuppression and shorter treatment time.

Moderately Hypofractionated Radiotherapy with Simultaneous Integrated Boost in Prostate Cancer: A Comparative Study with Conventionally Fractionated Radiation.

Background To report 5-year clinical outcomes and toxicity in organ-confined prostate cancer (PCa) for low- and intermediate-risk patients treated with a moderately hypofractionated schedule of radiotherapy (RT) delivered with simultaneous integrated boost (SIB) compared to a conventionally fractionated RT regimen. Methods Data of 384 patients with PCa treated between August 2006 and June 2017 were retrospectively reviewed. The treatment schedule consisted of hypofractionated RT (HYPO FR) with SIB up to 70 Gy to the prostate gland and 63 Gy to seminal vesicles delivered in 28 fractions or in conventionally fractionated RT (CONV FR) up to a total dose of 80 Gy in 40 fractions. Patient allocation to treatment was based on the time period considered. For intermediate-risk patients, androgen deprivation was given for a median duration of 6 months. The 5-year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), and overall survival (OS) were assessed. Furthermore, we evaluated gastrointestinal (GI) and genitourinary (GU) toxicities. Uni- and multivariate Cox regression analyses were used to test the impact of clinical variables on both outcome and toxicity. Results A total of 198 patients was treated with hypofractionated RT and 186 with the conventional schedule. At a median follow-up of 5 years, no significant differences were observed in terms of GI toxicity and outcome between the two groups. Early GU toxicity was significantly increased in HYPO FR, while late GU toxicity was significantly higher in CONV FR. In HYPO FR, a biochemical relapse occurred in 12 patients (6.1%), and 9 patients (4.5%) reported a clinical relapse (4 local, 2 locoregional, and 3 systemic recurrence). In CONV FR, 15 patients (8.1%) experienced a biochemical relapse and 11 patients (5.9%) showed a clinical relapse (5 local, 4 locoregional, and 3 systemic recurrences). Early grades 1-2 GU and GI toxicities were observed in 60 (30.3%) and 37 (18.7%) patients, respectively, in the hypofractionated group and in 33 (17.7%) and 27 (14.5%) patients, respectively, in the conventionally fractionated RT group. Late GU and GI toxicities occurred in 1 (0.51%) and 8 (4.1%) patients, respectively, in HYPO FR. In CONV FR, 5 (2.7%) and 6 (3.2%) patients experienced late GU and GI toxicities, respectively. The 5-year OS, bRFS, and CSS were 98.9%, 94.1%, and 99.5%, respectively, in HYPO FR, and 94.5%, 92.1%, and 99.0%, respectively, in CONV FR. Conclusions Results obtained in this study showed that moderately hypofractionated RT employing SIB can be an effective approach providing valuable clinical outcomes with an acceptable toxicity profile.

P017 - Acute toxicity in moderate hypofractionation with Simultaneous Integrated Boost (SIB) radiation therapy for prostate cancer: A prospective study

P017 - Acute toxicity in moderate hypofractionation with Simultaneous Integrated Boost (SIB) radiation therapy for prostate cancer: A prospective study

Toxicity and Dosimetric Analysis of Early Breast Cancer (EBC) Patients Treated with Ultra-Hypofractionated Weekly Radiotherapy (RT) and Simultaneous Integrated Tumor Bed Boost

EBC patients with advanced age, severe comorbidities/ logistic issues precluding daily treatment were offered ultra-hypofractionated once-weekly RT. For those women requiring additional tumor bed (TB) boost, a simultaneous integrated boost (SIB) was delivered to further reduce the number of hospital visits. We report feasibility and safety of this regimen in EBC patients. Thirty-seven patients of early breast cancer (T1N0: n = 17; T2N0: n = 20) treated from Dec 2018 -Feb 2020 at our institute with breast conservation were included in this study. They received 28.5Gy in 5 weekly fractions to entire breast and a SIB to the TB of 31.5-33Gy using VMAT technique along with image guidance in each fraction. Vacuum bag immobilization and volumetric image guidance with every fraction ensured accurate treatment delivery. The median age was 53 years (IQR: 50 - 61 years) where 19 patients (51%) had left breast cancer. Twenty-one patients (56.7%) had received adjuvant chemotherapy and 28 (75.7%) received concurrent hormonal therapy with RT. TB boost was recommended in view of grade III disease (n = 27), close/involved margins (n = 4), mucinous histology (n = 2) and young age (n = 4). Seven patients (19%) received a SIB doses of 32.5Gy and 27 (73%) received 33Gy. Dosimetric details are shown in table 1. At RT completion out of 30 patients 6, 23 and 1 patient showed RTOG Grade 0, I and II skin reaction respectively. The grade II skin reaction was seen in the axillary fold region within 4 fractions and was treated with the 5th fraction after replanning to underdose the area with skin fold. Once weekly whole breast RT with SIB to TB up to 33Gy in EBC appears to be a safe and feasible. Late toxicity of this regimen needs to be prospectively evaluated.Abstract 2126; TableDosimetric parametersParametersMean ValuesStandard DeviationInter-quartile rangePTV BreastVolume in cc898314.6650 – 1107V 95%96.9%1.5495.8- 98.4%PTV Tumor bedVolume in cc1105870.9 – 128.3V95%98.3%1.7997.3-99.5%Ipsilateral LungMean5.7Gy1.344.9- 6.3GyV5Gy35.7%10.1728.95- 42.1%V20Gy4.7%2.62.7-6.2 %Contralateral LungMean2.1Gy0.751.6- 2.5GyV5Gy5.4%5.10.99- 8.09%HeartMeanLeft -3.09Gy0.812.5-3.6GyRight-2.67Gy1.41.42-3.15GyV5GyLeft-15.3%9.069.4-18.4%Right-12.3%16.71.89-17.65%Left Anterior Descending ArteryMax dose (0.03cc)Left 11.1Gy1.999.3-12.8GyRight 3.8Gy1.492.5-5.1GyBrachial plexusMax dose9.29Gy7.361.6-15.4GyContralateral BreastMean2.4Gy0.811.6- 3.06GyConformity index tumor bedMedian1.080.251.03-1.12 Open table in a new tab