Simultaneous Integrated Boost Technique Research Articles

Comparing different boost concepts and beam configurations for proton therapy of pancreatic cancer

Background and PurposeInterfractional geometrical and anatomical variations impact the accuracy of proton therapy for pancreatic cancer. This study investigated field-in-field (FIF) and simultaneous integrated boost (SIB) concepts for scanned proton therapy treatment with different beam configurations. Materials and MethodsRobustly optimized treatment plans for fifteen patients were generated using FIF and SIB techniques with two, three, and four beams. The prescribed dose in 20 fractions was 60 Gy(RBE) for the internal gross tumor volume (IGTV) and 46 Gy(RBE) for the internal clinical target volume. Verification computed tomography (vCT) scans was performed on treatment days 1, 7, and 16. Initial treatment plans were recalculated on the rigidly registered vCTs. V100% and D95% for targets and D2cm3 for the stomach and duodenum were evaluated. Robustness evaluations (range uncertainty of 3.5 %) were performed to evaluate the stomach and duodenum dose-volume parameters. ResultsFor all techniques, IGTV V100% and D95% decreased significantly when recalculating the dose on vCTs (p < 0.001). The median IGTV V100% and D95% over all vCTs ranged from 74.2 % to 90.2 % and 58.8 Gy(RBE) to 59.4 Gy(RBE), respectively. The FIF with two and three beams, and SIB with two beams maintained the highest IGTV V100% and D95%. In robustness evaluations, the ΔD2cm3 of stomach was highest in two beams plans, while the ΔD2cm3 of duodenum was highest in four beams plans, for both concepts. ConclusionTarget coverage decreased when recalculating on CTs at different time for both concepts. The FIF with three beams maintained the highest IGTV coverage while sparing normal organs the most.

Ultrahypofractionated Radiation Therapy for Prostate Cancer Including Seminal Vesicles in the Target Volume: A Treatment-planning Study Based on the HYPO-RT-PC Fractionation Schedule

PurposeUltra-hypofractionated (UHF) radiation therapy (RT) has become a treatment alternative for patients with localized prostate cancer. In more advanced cases, seminal vesicles (SV) are routinely included in the target volume. The Scandinavian HYPO-RT-PC trial, which compared 42.7Gy in 7 fractions (fr) to conventional fractionation (CF), did not include SV in the CTV. The primary objective of the present work is to implement a UHF simultaneous integrated boost (SIB) for prostate cancer RT, incorporating SV into the target volume based on this fractionation schedule. A secondary objective is to analyze the unintentional dose coverage of SV from state-of-the-art VMAT treatments to the prostate gland only. Material and MethodsTwo different equi-effective UHF-SIB treatment schedules to SV were derived based on the CF clinical schedule (50.0Gy/25fr to elective SV and 70.0Gy/35fr to verified SV-invasion (SVI)) using the linear quadric model with α/β=2Gy and 3Gy. The dose to the prostate was 42.7Gy/7fr in both schedules with 31.2Gy/37.8Gy (α/β=2Gy) and 32.7Gy/40.1Gy (α/β=3Gy) to elective SV/verified SVI. VMAT plans to the proximal 10mm and 20mm were optimized and dose-volume-metrics for target volumes and organs at risk (OAR) evaluated. ResultsDose metrics were overall lower for UHF-SIB compared to CF. QUANTEC based volume-criteria are 2-7% lower for rectum and 2-4% lower for bladder in the UHF-SIB. D98% to elective SV were 7-12Gy3 lower with UHF-SIB and the corresponding data for verified SVI were about 2-3Gy3. The SV(10mm) V90%/(29.5Gy) for prostate only treatments (42.7Gy) were in median (IQR) 99% (87-100)/ 78% (58-99) for CTV/PTV. ConclusionUHF RT, based on the HYPO-RT-PC fractionation schedule, with a SIB technique to the prostate and the base of the SV can be planned with lower doses (EQD2) to OARs compared to CF. Unintentional dose to the proximal parts of SV in prostate only treatment can be substantial.

Dose-escalated Salvage Whole-pelvic Radiotherapy for Biochemical Recurrence After Radical Prostatectomy for High-risk Prostate Cancer.

To investigate the institutional experience of dose-escalated salvage whole-pelvic radiotherapy (WPRT) with the simultaneous integrated boost (SIB) technique in patients with biochemical recurrence (BCR) after radical prostatectomy for high-risk prostate cancer. This retrospective study included 21 patients with BCR who received radical prostatectomy for high-risk prostate cancer and underwent salvage RT. Clinical target volume (CTV) of the whole pelvis (CTV56) included the prostate bed, common iliac, external iliac, internal iliac, and obturator lymph node regions. The boost CTV (CTV66) included the prostate bed. Planning target volumes (PTV) were generated by adding a margin of 6-8 mm to CTV (PTV56 and PTV66). Doses of 56.1 and 66 Gy in 33 fractions were delivered to PTV56 and PTV66, respectively. The 5-year biochemical progression-free survival, overall survival, and cause-specific survival rates were 72%, 94%, and 94%, respectively. A grade 3 late genitourinary toxicity event of gross hematuria was observed in one patient (4%). Acute and late toxicities of grade ≥3, other than gross hematuria, were not observed in any patient. Dose-escalated salvage WPRT using the SIB technique provides appropriate tumor control without increasing the incident of significant toxicities.

Prospective results for 5-year survival and toxicity of moderately hypofractionated radiotherapy with simultaneous integrated boost (SIB) in (very) high-risk prostate cancer

PurposeHigh-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. MethodsPatients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. ResultsWe recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. ConclusionSIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.

Treatment Outcomes of Simultaneous Integrated Boost to Intraprostatic Lesions with External Beam Radiotherapy in Localized Prostate Cancer Patients.

To evaluate the treatment outcomes and toxicity of definitive radiotherapy (RT) for prostate cancer (PC) patients using the simultaneous integrated boost (SIB) technique to intraprostatic lesion (IPL). All the patients received 78 Gy for their prostate ± seminal vesicles and 86 Gy for the IPL using the SIB technique. High-risk patients received pelvic nodal irradiation. The pelvic lymphatic field received 46-54 Gy of radiation. Univariable and multivariable analyses were conducted of the prognostic factors for freedom from biochemical failure (FFBF), progression-free survival (PFS), and PC-specific survival (PCSS) of 619 PC patients who received definitive RT between September 2012 and August 2021. Predictors of late Grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities were also identified using logistic regression. The median age of the entire cohort was 69 years (range, 47-89 years). Most of the patients (82.7%) had tumors with a GS of 6 or 7, 134 (21.6%) had PC with a GS of 3 + 4, 126 (20.4%) had PC with a GS of 4 + 3, and only 9% had clinical nodal metastasis. The median follow-up time for the entire cohort was 68.5 months (95% CI, 64.4-72.6 months). The 5-year FFBF, PFS, and PCSS rates were 93.2%, 83.2%, and 98.6%, respectively. They were predicted by the serum prostate specific antigen (PSA), Gleason score (GS), clinical nodal stage, and D'Amico risk group. Only 45 patients (7.3%) developed disease recurrence 41.9 months after RT. Of these patients, 12 (1.9% of the total) had BF only, 31 (5.3%) had both BF and distant metastasis, and 2 (0.3%) had distant metastasis only. The 5-year FFBF rates for low-, intermediate-, and high-risk disease were 98.0%, 93.1%, and 88.5%, respectively (p < 0.001). The 5-year PFS and PCSS rates according to risk groups were 91.0%, 82.1%, and 77.4% (p < 0.001), and 99.2%, 96.4%, and 95.9% (p = 0.03), and respectively. GS > 7 and lymph node metastasis negatively predicted FFBF and PCSS in multivariable analysis. Lymph node metastasis was associated with poor PFS, but only marginally (p = 0.06). Ninety (14.6%) and 44 (7.1%) patients had acute Grade ≥ 2 GU and GI toxicities, respectively, and 42 (6.8%) and 27 (4.4%) patients had late Grade ≥ 2 GU and GI toxicities, respectively. Diabetes (OR = 2.61; 95% CI = 1.29-5.26; p = 0.007) and transurethral resection of prostate (OR = 6.75; 95% CI = 3.37-13.54; p = 0.001) independently predicted late Grade ≥ 2 GU toxicity, but no significant predictor of late Grade ≥ 2 GI toxicity was found. Localized PC was effectively and safely treated with definitive RT using the SIB technique to deliver 86 Gy to the IPL in 39 fractions without severe late toxicity. This finding must be validated with long-term results.

Clinical Outcomes of Sidewall/Parametrial Simultaneous Integrated Boost for Patients with Cervical Cancer

In the treatment of cervical cancer, simultaneous integrated boost (SIB) is a common technique to deliver increased dose to gross disease in the para-aortic and pelvic nodal basins. However, SIB to the pelvic sidewall/parametria is not well characterized in the literature. We hypothesized that sidewall simultaneous integrated boost (SIB) in the treatment of cervical cancer is associated with acceptable levels of toxicity. From 1/2009-12/2018, patients who received concurrent chemoradiation with external beam radiation therapy, utilizing a sidewall SIB technique, followed by low dose rate or high dose rate brachytherapy treatment were retrospectively identified. Sidewall SIB was defined as treatment at 2.1-2.4Gy/fraction to the parametria-usually performed for those with disease width >4cm at time of treatment start. Acute and late toxicity grading was defined by the Common Terminology Criteria for Adverse Events Version 5.0. Overall survival (OS), local control, progression-free survival (PFS), and toxicity were analyzed utilizing the Kaplan Meier method. Potential associations between cumulative D2cc for bladder and rectum and time to toxicity were investigated using Cox regression. Fifty-six patients with IB2-IVB cervical cancer treated with sidewall SIB were identified, with a median follow up of 7.0 years (95% CI: 6.3, 8.3). Patients had a median age of 43 years (range: 26-68); 2 (3.6%) had FIGO stage I, 7 (12.5%) stage II, 46 (82.1%) stage III, and 1 (1.8%) stage IV disease. A majority had squamous cell histology (83.9%). Nearly all patients (96.4%) received concurrent cisplatin chemotherapy. Rates of acute grade ≥3 gastrointestinal (GI), genitourinary (GU), vaginal, and hematologic toxicity were 1.8%, 1.8%, 0%, and 15.9% respectively. Rates of late grade ≥3 GI, GU, and vaginal toxicity were 11.3%, 18.5%, and 11.1% respectively. OS and local control rates at five years were 0.61 (95% CI: 0.46, 0.73) and 0.95 (95% CI: 0.84, 0.98), respectively. Median PFS was 7.8 years (95% CI: 2.4, Not reached). Cumulative D2cc bladder was not significantly associated with time to Grade 2 or greater (HR 1.04, p = 0.33) or Grade 3 or greater (HR 1.02; p = 0.64) GU toxicity. Cumulative D2cc rectum was not significantly associated with time to Grade 2 or greater (HR 1.06, p = 0.06) or Grade 3 or greater (HR 1.08; p = 0.09) GI toxicity. Sidewall SIB is a feasible technique for dose escalation in the treatment of cervical cancer with rates of acute and late toxicity consistent with other reports.

Comparison of intraoperative radiotherapy as a boost vs. simultaneously integrated boosts after breast-conserving therapy for breast cancer.

Currently, there are no data from randomized trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost in women at high risk of local recurrence. The aim of this retrospective analysis was to compare the toxicity and oncological outcome of IORT or simultaneous integrated boost (SIB) with conventional external beam radiotherapy (WBI) after breast conserving surgery (BCS). Between 2009 and 2019, patients were treated with a single dose of 20 Gy IORT with 50 kV photons, followed by WBI 50 Gy in 25 or 40.05 in 15 fractions or WBI 50 Gy with SIB up to 58.80-61.60 Gy in 25-28 fractions. Toxicity was compared after propensity score matching. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. A 1:1 propensity-score matching resulted in an IORT + WBI and SIB + WBI cohort of 60 patients, respectively. The median follow-up for IORT + WBI was 43.5 vs. 32 months in the SIB + WBI cohort. Most women had a pT1c tumor: IORT group 33 (55%) vs. 31 (51.7%) SIB group (p = 0.972). The luminal-B immunophenotype was most frequently diagnosed in the IORT group 43 (71.6%) vs. 35 (58.3%) in the SIB group (p = 0.283). The most reported acute adverse event in both groups was radiodermatitis. In the IORT cohort, radiodermatitis was grade 1: 23 (38.3%), grade 2: 26 (43.3%), and grade 3: 6 (10%) vs. SIB cohort grade 1: 3 (5.1%), grade 2: 21 (35%), and grade 3: 7 (11.6%) without a meaningful difference (p = 0.309). Fatigue occurred more frequently in the IORT group (grade 1: 21.7% vs. 6.7%; p = 0.041). In addition, intramammary lymphedema grade 1 occurred significantly more often in the IORT group (11.7% vs. 1.7%; p = 0.026). Both groups showed comparable late toxicity. The 3- and 5-year local control (LC) rates were each 98% in the SIB group vs. 98% and 93% in the IORT group (LS: log rank p = 0.717). Tumor bed boost using IORT and SIB techniques after BCS shows excellent local control and comparable late toxicity, while IORT application exhibits a moderate increase in acute toxicity. These data should be validated by the expected publication of the prospective randomized TARGIT-B study.

Treatment outcomes of simultaneous integrated boost to intraprostatic lesions with external beam radiotherapy in localized prostate cancer patients.

To evaluate the treatment outcomes and toxicity of definitive radiotherapy (RT)for prostate cancer (PC)patients using the simultaneous integrated boost (SIB)technique, which delivered 78 Gy to the entire prostate and 86 Gy to the intraprostatic lesion (IPL)in 39 fractions. Univariable and multivariable analyses were conducted of the prognostic factors for freedom from biochemical failure (FFBF),progression-free survival (PFS),and PC-specific survival (PCSS)of 619 PC patients who received definitive RT between September 2012 and August 2021. Predictors of late Grade ≥2 genitourinary (GU)and gastrointestinal (GI)toxicities were also identified using logistic regression. The median follow-up for entire cohort was 68.5 months. The 5-year FFBF, PFS, and PCSS rates were 93.2%, 83.2%, and 98.6%, respectively. They were predicted by the serum prostate-specific antigen,Gleason score (GS),clinical nodal stage, and D'Amico risk group. Only 45 patients (7.3%) developed disease recurrence 41.9 months after RT. The 5-year FFBF rates for low-, intermediate-, and high-risk disease were 98.0%, 93.1%, and 88.5%, respectively (p < 0.001). The 5-year PFS and PCSS rates according to risk groups were 91.0%, 82.1%, and 77.4% (p < 0.001), and 99.2%, 96.4%, and 95.9% (p = 0.03), and, respectively. GS > 7 and lymph node metastasis negatively predicted FFBF and PCSS in multivariable analysis. Ninety (14.6%) and 44 (7.1%) patients had acute Grade ≥2 GU and GI toxicities, respectively, and 42 (6.8%) and 27 (4.4%) patients had late Grade ≥2 GU and GI toxicities, respectively. Diabetes and transurethral resection independently predicted late Grade 2 GU toxicity, but no significant predictor of late Grade ≥2 GI toxicity was found. Localized PC was effectively and safely treated with definitive RT using the SIB technique to deliver 86 Gy to the IPL in 39 fractions without severe late toxicity. This finding must be validated with long-term results.

A RARE CASE OF INTRAOSSEOUS MUCOEPIDERMOID CARCINOMA OF MAXILLA TREATED AT OUR CENTRE.

Occurrence of Primary intraosseous mucoepidermoid carcinoma (PIOC) within the jaw bones from aberrant salivary tissues is extremely rare. Mandible is more commonly affected but occurrence in maxilla is very rare. The origin of mucoepidermoid carcinoma is controversial and debatable. Primary Intraosseous mucoepidermoid carcinoma is frequently misdiagnosed radiographically and clinically as a benign odontogenic tumor or cyst.Primary Intraosseous Mucoepidermoid Carcinoma has distinct and specic radiological and morphological features for its diagnosis. The main modality of treatment is surgery and appropriate patients are offered adjuvant radiotherapy. This paper reports a case of central mucoepidermoid carcinoma of the Maxilla which was presented as complaints of pain and swelling of upper jaw.Then, he was treated with surgery followed by adjuvant treatment as per specimen pathological report. Here, we have used Simultaneous Integrated Boost technique with helical IMRT for Radiotherapy along with concurrent chemotherapy for treatment of revised margins following positive margins status. Central mucoepider Summary: moid carcinoma is a rare entity with highly selective radiological, histological and immunohistochemical criteria with overall around 150 cases reported. Due to rarity of occurrence, consensus guidelines for treatment protocol have not been established. Here we have described a similar case of a 25yrs old male patient that was diagnosed, surgically resected and has completed adjuvant chemo-radiation therapy at our centre

The Outcomes of Definitive Radiotherapy in Patients with Prostate Cancer Using Simultaneous Integrated Boost Technique

<h3>Purpose/Objective(s)</h3> Previous studies had shown a dose-response relationship in prostate cancer during radiotherapy (RT). The clinical outcomes of prostate cancer patients treated with definitive RT using the simultaneous-integrated boost (SIB) technique were investigated in this study. <h3>Materials/Methods</h3> The clinical data of 556 prostate cancer patients who underwent RT using the SIB technique between September 2012 and September 2021 were retrospectively analyzed. In 39 fractions, patients received 78 Gy to the entire prostate±seminal vesicles and 86 Gy to the intraprostatic lesion (IPL). In addition, high-risk patients received 54 Gy pelvic field irradiation. Diffusion-weighted magnetic resonance imaging was used to define the IPL. Failure from biochemical failure (FFBF) and prostate-cancer specific survival (PCSS) were the primary endpoints. Secondary endpoints were progression free survival (PFS) and toxicity. <h3>Results</h3> The median age of the population was 69 years (range: 47–89 years). According to D'Amico risk categories, there were 175 patients (31.5%) classified as low risk, 186 patients (33.4%) classified as intermediate risk, and 195 patients (35.1%) classified as high risk. 253 patients (54.5%) received androgen deprivation therapy. The median duration of follow-up was 58.2 months (range, 4.7–126.8 months) for the entire cohort. The 5-year FFBF, PCSS, and PFS rates were respectively 93.3%, 98.5%, and 84.1%. In 40 patients (7.2%), progression was observed as biochemical failure in 16 patients, distant metastasis in 2 patients, and both biochemical failure and distant metastasis in 22 patients. Only four patients (0.7%) had a local recurrence. Univariate analysis revealed that the pretreatment PSA value, T and N stages, ISUP score, and D'Amico risk groups were all significant prognostic factors for FFBF and PCSS. PSA levels higher than 20 ng/mL [HR=3.39 (95% CI, 1.28–8.94); p=0.01], nodal metastasis [HR=4.03 (95% CI, 1.61–10.03); p=0.003], high risk disease [HR=6.66 (95% CI, 1.72–25.77); p=0.001], and higher ISUP scores [HR=2.31 (95% CI, 1.53–3.49); p<0.001] were all independent predictors of worse FFBF. In multivariable analysis, the significant predictors of worse PCSS were high risk disease [HR=8.96 (95% CI: 2.13–19.71; p=0.01] and a higher ISUP score [HR=12.21 (95% CI: 1.70–87.74; p=0.004]. Acute gastrointestinal (GI) and genitourinary (GU) system toxicities of grade 2 or greater were observed in 7.4% and 14.0% of patients, respectively. Late GI and GU toxicities of grade 2 or greater were observed in 5.3% and 6.9% of patients, respectively. <h3>Conclusion</h3> The treatment strategy of 78 Gy delivered to the entire prostate with a boost dose of 86 Gy to IPL was effective and safe, with excellent biochemical control and PCSS, and very low toxicity rates. Longer follow-up and randomized trials are needed to validate our findings.

Simultaneous Integrated Boost Technique for Pediatric High-Grade Gliomas: A Single-Institution Experience

<h3>Purpose/Objective(s)</h3> The prognosis for pediatric patients with high grade glioma (HGG) remains dismal despite aggressive multidisciplinary treatment, and there is marked variability regarding the optimal radiation approach. We report outcomes from a retrospective review of pediatric patients with HGG treated using a simultaneous integrated boost (SIB) technique at a single institution. <h3>Materials/Methods</h3> The medical records of patients ages 0–22y with biopsy-proven non-DIPG localized HGG treated with radiotherapy (RT) from January 2006 to May 2021 were retrospectively reviewed on an IRB approved protocol. Endpoints were Kaplan-Meier estimates of overall survival (OS) and progression free survival (PFS), and patterns of failure. <h3>Results</h3> There were 32 patients in the cohort; 24 patients had glioblastoma without further molecular characterization, 2 had H3 K27M mutant diffuse midline gliomas, 2 had G34R mutant glioma, 2 had glioblastoma with IDH1 mutation, 1 had high-grade astrocytoma, and 1 had high-grade glial neoplasm. Median age at diagnosis was 14.9 (1.9–21.5) years. Prior to RT, 6 patients obtained both spinal MRIs and lumbar punctures, 5 obtained spinal MRIs, and 1 had a lumbar puncture; none had evidence of distant metastases. All patients were treated with intensity modulated radiotherapy (IMRT) using SIB with two dose levels. The most common (n=25) dose to the high dose volume was 60 Gy (range, 40–60 Gy); the most common (n=24) dose to the low dose volume was 50 Gy (range, 30–55 Gy). Treatment was most commonly (n=26) delivered in 30 fractions (range, 15-33). One patient did not complete planned RT due to tumor hemorrhage. Median follow up for all patients was 17 (0–164.4) months. For patients who completed planned RT, median PFS was 20.1 (1–140) months from RT start. Median OS was 25.9 months with one- and two-year survival rates of 80% and 56%, respectively. Of 19 patients with known recurrence, 8 recurred locally, 7 recurred in the distant brain, and 4 developed leptomeningeal dissemination. Three patients were alive at 10 years after initial diagnosis; none of these patients were known to have tumors with IDH mutations. <h3>Conclusion</h3> This study explores outcomes in a cohort of pediatric HGG patients treated with SIB technique, with encouraging initial results. Future efforts will be necessary to identify additional molecular and treatment factors that impact outcome.

Patient-Reported Rectal QOL with Pelvic Nodal Irradiation ± Involved Pelvic Nodal Boost to 75 Gy EQD2 in Men with Prostate Cancer

<h3>Purpose/Objective(s)</h3> The study was designed to compare patient-reported acute and late rectal function quality of life (RQOL) between men with local or regional prostate cancer treated with or without an involved pelvic nodal simultaneous integrated boost (SIB). It is hypothesized that men receiving pelvic nodal radiotherapy at 50.4 Gy in 28 fractions (Pelv50) have similar RQOL as men receiving the same pelvis dose plus the addition of involved pelvic nodal SIB to 67.2 Gy in 28 fractions (Pelv67). <h3>Materials/Methods</h3> Rectal toxicity was assessed using the Merrick Rectal Function Assessment Score (R-FAS). The R-FAS consists of nine questions and a scoring range of 0-27, with higher scores indicating poorer bowel function. Patients with measures -180 days and up to 730 days from the start of RT were included in the analysis. SIB targets included radiographically apparent nodal GTVs plus a 5mm margin. Pelvic nodal contours extended from aortic bifurcation through the bilateral obturator nodes. An EQD2 of 75 Gy to involved nodal targets was calculated for the Pelv67 group based on 28 fractions of 2.4 Gy with an α/β ratio of 1.5. Patients were dichotomized by treatment received (Pelv50 vs. Pelv67). Non-parametric kernel regression was modeled with R-FAS score as the dependent variable and time from RT and treatment cohort as the independent variables, with improved Akaike information criterion to determine optimal bandwidth. Marginal means and 95% confidence intervals were predicted at 90-day intervals from timepoint 0 with 50 bootstrapping replications. <h3>Results</h3> There was no difference in baseline age or baseline Charlson Comorbidity Index between the two cohorts. There was no significant difference in mean R-FAS over the entire time interval between the two cohorts (Pelv67 vs. Pelv50: 0.4 points, p=0.17). There is no significant difference in R-FAS score at any discrete timepoint between Pelv67 and Pelv50 as the 95% confidence intervals overlap (Table). <h3>Conclusion</h3> Pelvic nodal irradiation with a simultaneous integrated boost to 67.2 Gy in 28 fractions (EQD2=75 Gy) was associated with similar rates of RQOL compared to standard pelvic irradiation from the patient's perspective. This study suggests that dose escalation using a pelvic nodal SIB technique to 75Gy EQD2 is safe despite the proximity of the rectum and bowel to SIB targets.

Carbon Ion Radiotherapy Induce Metabolic Inhibition After Functional Imaging-Guided Simultaneous Integrated Boost for Prostate Cancer.

PurposeAs local recurrence remains a challenge and the advantages of the simultaneous integrated boost (SIB) technique have been validated in photon radiotherapy, we applied the SIB technique to CIRT. The aim was to investigate the metabolomic changes of the CIRT with concurrent androgen deprivation therapy (ADT) in localized prostate cancer (PCa) and the unique metabolic effect of the SIB technique.Material and MethodsThis study enrolled 24 pathologically confirmed PCa patients. All patients went through CIRT with concurrent ADT. The gross target volume (GTV) boost was defined as positive lesions on both 68Ga-PSMA PET/CT and mpMRI images. Urine samples collected before and after CIRT were analyzed by the Q-TOF UPLC-MS/MS system. R platform and MetDNA were used for peak detection and identification. Statistical analysis and metabolic pathway analysis were performed on Metaboanalyst.ResultsThe metabolite profiles were significantly altered after CIRT. The most significantly altered metabolic pathway is PSMA participated alanine, aspartate and glutamate metabolism. Metabolites in this pathway showed a trend to be better suppressed in the SIB group. A total of 11 identified metabolites were significantly discriminative between two groups and all of them were better down-regulated in the SIB group. Meanwhile, among these metabolites, three metabolites in DNA damage and repair related purine metabolism were down-regulated to a greater extent in the SIB group.ConclusionMetabolic dysfunction was one of the typical characteristics of PCa. CIRT with ADT showed a powerful inhibition of PCa metabolism, especially in PSMA participated metabolic pathway. The SIB CIRT showed even better performance on down-regulation of most metabolism than uniform-dose-distribution CIRT. Meanwhile, the SIB CIRT also showed its unique superiority to inhibit purine metabolism. PSMA PET/CT guided SIB CIRT showed its potentials to further benefit PCa patients.

Dosimetric Comparison of Intensity Modulated Radiotherapy and Simultaneous Integrated Boost Techniques in the Treatment of Glioblastoma Multiforme

Dosimetric Comparison of Intensity Modulated Radiotherapy and Simultaneous Integrated Boost Techniques in the Treatment of Glioblastoma Multiforme

Different treatment planning strategies for whole-brain radiation therapy with simultaneous integrated boost for multiple brain metastases to protect neurocognitive function with hippocampal sparing

PURPOSE: The aim of this study is to provide the dosimetric evaluation of the compound therapeutic concept of hippocampal avoidance for the whole brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) in patients with multiple brain metastases more than 3.MATERIALS AND METHODS: Ten patients with multiple brain metastases previously treated with conventional WBRT followed by SIB on Radixact Tomotherapy Unit were selected. The whole-brain (WB) clinical target volume was generated by contouring the WB and excluding the hippocampal avoidance structure for the sake of WBRT while plan optimization of both approaches was performed with the aim of delivering 95% of the WB and receiving the prescription dose of 30 Gy; in addition, planning target volumes (PTVs) were given 45 Gy using SIB technique in 10 fractions. Dmax ≤16 Gy and D100% ≤9 Gy for hippocampi and V37 Gy for the WB-PTVs were evaluated in this study as well.RESULTS: The D95% was 44.8 ± 0.15 Gy in helical tomotherapy (HT) which was calculated as 44.9 ± 0.11 Gy in volumetric modulated arc therapy (VMAT) plan. The volume receiving 37 Gy for brain-PTV was 3% ± 0.55% in HT and 10% ± 1.55% in the VMAT plan. The D2% and D100% values of hippocampi were calculated <2 Gy in HT plan compared to the VMAT plan.CONCLUSION: Techniques used in both plans are feasible. However, the VMAT plan owns the ability to deliver SIB dose to each individual metastasis as well while it adequately delivers WBRT and conformably spares the hippocampus. On the negative side, providing the dosimetric criteria of hippocampus is not possible in some cases due to the close proximity of tumor locations to the hippocampus.

In Silico Feasibility Study of Carbon Ion Radiotherapy With Simultaneous Integrated Boost for Head and Neck Adenoid Cystic Carcinoma.

PurposeIn carbon ion radiotherapy (CIRT), a simultaneous integrated boost (SIB) approach has not been fully exploited so far. The feasibility of a CIRT-SIB strategy for head and neck adenoid cystic carcinoma (ACC) patients was investigated in order to improve treatment planning dose distributions.Methods and MaterialsCIRT plans of 10 ACC patients treated at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) with sequential boost (SEQ) irradiation and prescription doses of 41.0 Gy [relative biological effectiveness (RBE)]/10 fractions to low-risk (LR) clinical target volume (CTV) plus 24.6 Gy(RBE)/6 fractions to the high-risk (HR) CTV were re-planned with two SIB dose levels to the LR-CTV, namely, 48.0 Gy(RBE) and 54.4 Gy(RBE). While planning with SIB, the HR-CTV coverage had higher priority, with fixed organ-at-risk dose constraints among the SIB and SEQ plans. The homogeneity and conformity indexes were selected for CTV coverage comparison. The biologically effective dose (BED) was calculated to compare the different fractionation schemes.ResultsComparable HR-CTV coverage was achieved with the treatment approaches, while superior conformality and homogeneity were obtained with the SIB technique in both CTVs. With the SEQ, SIB48.0, and SIB54.4, the LR-CTV median doses were respectively 50.3%, 11.9%, and 6.0% higher than the prescriptions. Significant reductions of the median and near-maximum BEDs were achieved with both SIB dose levels in the LR-CTV.ConclusionsThe SIB approach resulted in highly conformal dose distributions with the reduction of the unintended dose to the LR-CTV. A prescription dose range for the LR-CTV will be clinically defined to offer tailored personalized treatments, according to the clinical and imaging characteristics of the patients.

Hypofractionated Radiation Therapy (HFRT) of Breast/Chest Wall and Regional Nodes in Locally Advanced Breast Cancer: Toxicity Profile and Survival Outcomes in Retrospective Monoistitutional Study

AIMTo evaluate the efficacy and safety of hypofractionated radiation therapy (HFRT) of the breast/chest wall and regional nodes in patients with locally advanced breast cancer and positive lymph nodes. Materials and MethodsOne hundred and twenty-two patients treated between October 2016 and March 2020 with HFRT were retrospectively reviewed. A total dose of 42.4 Gy was delivered to the chest wall and lymph nodes in 16 fractions of 2.65 Gy each, using the IMRT technique. Patients treated with breast-conserving surgery received an overdose (concomitant boost of 3 Gy daily) with the SIB (Simultaneous Integrated Boost) technique. ResultsMedian age at diagnosis was 58 years (range 34-86 years) and median follow-up was 22 months (range 6-48 months). Overall survival (OS) at 1, 2 and 3 years was 100%, 97.3% and 90%, respectively. Disease-free survival (DFS) at 1, 2, and 3 years was 91.4%, 87%, and 84.8%, respectively. Distant metastasis-free survival (MFS) at 1, 2 and 3 years was 93.1%, 88% and 85.7%, respectively. Two patients (1.6%) experienced local recurrence on the chest wall during FUP. Twenty-one patients (17%) showed a grade 2 dermal toxicity, no grade 3 acute skin toxicity was found. Sixteen patients (13%) showed early-stage arm lymphedema (grade ≤ 2). Twenty-three patients (19%) showed a grade 2 late skin toxicity. Twenty patients (16%) had grade ≤ 2 late arm lymphedema. ConclusionGiven the excellent local control, survival rates and the low toxicity profile demonstrated, HFRT could be considered a valid therapeutic option in patients with locally advanced breast cancer.

Investigate the Dosimetric and Potential Clinical Benefits Utilizing Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost Technique for Locally Advanced Pancreatic Cancer: A Comparison Between Photon and Proton Beam Therapy.

PurposeTo investigate the potential clinical benefits of using stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) technique for locally advanced pancreatic cancer (LAPC) among different treatment modalities and planning strategies, including photon and proton.MethodA total of 19 patients were retrospectively selected in this study: 13 cases with the tumor located in the head of the pancreas and 6 cases with the tumor in the body of the pancreas. SBRT-SIB plans were generated using volumetric modulated arc therapy (VMAT), two-field Intensity Modulated Proton Therapy (IMPT), and three-field IMPT. The IMPT used the robust optimization parameters of ± 3.5% range and 5-mm setup uncertainties. Root-mean-square deviation dose (RMSD) volume histograms were used to evaluate the target coverage robustness quantitatively. Dosimetric metrics based on the dose-volume histogram (DVH), homogeneity index (HI), and normal tissue complication probability (NTCP) were analyzed to evaluate the potential clinical benefits among different planning groups.ResultsWith a similar CTV and SIB coverage, two-field IMPT provided a lower maximum dose for the stomach (median: 18.6GyE, p<0.05) and duodenum (median: 32.62GyE, p<0.05) when the target was located in the head of the pancreas compared to VMAT and three-field IMPT. The risks of gastric bleed (3.42%) and grade ≥ 3 GI toxicity (4.55%) were also decreased. However, for the target in the body of the pancreas, VMAT showed a lower maximum dose for the stomach (median 30.93GyE, p<0.05) and toxicity of gastric bleed (median: 8.67%, p<0.05) compared to two-field IMPT and three-field IMPT, while other maximum doses and NTCPs were similar. The RMSD volume histogram (RVH) analysis shows that three-field IMPT provided better robustness for targets but not for OARs. Instead, three-field IMPT increased the Dmean of organs such as the stomach, duodenum, and intestine.ConclusionThe results indicated that the tumor locations could play a critical role in determining clinical benefits among different treatment modalities. Two-field IMPT could be a better option for LAPC patients whose tumors are located in the head of the pancreas. It provides lower severe toxicity for the stomach and duodenum. Nevertheless, VMAT is preferred for the body with better protection for the possibility of gastric bleed.

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.