Boost Intensity Modulated Radiation Therapy Research Articles

PO0248: MRI-Guided Intensity-Modulated Radiotherapy Boost in Gynecologic Cancers for Patients Unsuitable for Brachytherapy (BT): A Case Series

PO0248: MRI-Guided Intensity-Modulated Radiotherapy Boost in Gynecologic Cancers for Patients Unsuitable for Brachytherapy (BT): A Case Series

Simultaneous integrated boost-intensity modulated radiation therapy (SIBIMRT) planning for pelvic tumours: dose coverage to target volume and normal tissue sparing.

To evaluate the better radiotherapy plan for pelvic tumours that may achieve a high target coverage dose and low normal tissue tolerance dose using simultaneous integrated boost-intensity-modulated radiation therapy technique. The analytical, cross-sectional, descriptive study was conducted from October 2020 to March 2021 at Al- Amal National Hospital for Cancer Treatment, Baghdad, Iraq, and comprised male pelvic cancer patients aged 50-80 years. Computed tomography scans were randomly selected. For each patient, 4 treatment plans (phases Ι and Π) were generated using the simultaneous integrated boost-intensity-modulated radiation therapy technique while keeping all parameters constant except the number of beams, which were 5, 7, 9 and 11. The optimal and safe dose was defined as the one to cover 95% planning target volume. Homogeneity and conformity indices were used to assess the uniformity of dose distribution in the target volume, and various treatment plans in the same patient were compared. Data was analysed using SPSS 24. There were 15 males with mean age 67.12±2.84 years. There was a significant variance in the target volume dose and organ at risk in the 4 different plans generated using the simultaneous integrated boost-intensitymodulated radiation therapy technique (p<0.05). The 9-beam treatment plan was the best for coverage of tumours and protection of healthy organs assessed through homogeneity and conformity indices (p<0.05). The 9-beam treatment plan showed significant tumour coverage, homogeneity and conformity values, and sparing dose for organs at risk.

Volumetric Response and Survival of Patients With Bulky IDH-Mutated Grade 3 Glioma Managed With FET-FDG–Guided Integrated Boost IMRT

AimsDespite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain regions, prompting concern over both durable disease control and the morbidity associated with large volume radiation therapy. This study audits volumetric response, survival and functional outcomes in this ‘large volume’ subgroup that undergoes intensity modulated radiation therapy (IMRT). Materials and methodsFrom a prospective database of 187 patients with IDH-mutant grade 3 gliomas managed with IMRT between 2008 and 2020, recorded PTV was divided into quartiles. The top quartile, termed the ‘large volume cohort’ (LVC), was identified. IMRT involved FET-FDG guided integrated boost (59.4/54Gy in 33 fractions). Manual volumetric segmentation of baseline, four months and 13 months post-IMRT tumour were performed for T1, T2 and T1gd MRI sequences. The primary endpoint was volumetric reduction on the T1 and T2 sequences at 13 months and analysed with relapse-free survival (RFS) and overall survival (OS). Morbidity endpoints were assessed at year four post-IMRT and included performance status (ECOG PS) and employment outcomes. ResultsThe fourth quartile (LVC) identified 44 patients for whom volumetric analysis was available. The LVC had median PTV of 320cm3 compared to 186.2cm3 for the total group. Anaplastic astrocytoma and oligodendroglioma were equally distributed and tumour sites were frontal (54%), temporal (18%) and parietal lobes (16%).Median follow-up for survivors was 71.5 months. Projected 10-year RFS and OS in LVC was 40% and 62%, compared to 53% and 62% respectively in the overall cohort. The RFS (p = 0.06) and OS (p = 0.65) of the LVC was not significantly different to other PTV quartiles; however the impact of PTV volume reached significance when analysed as a continuous variable (RFS p < 0.01; OS p = 0.02).Median T1 volumes were 26.1cm3, 8.0cm3 and 5.3cm3 at months +0, +3 and +12, respectively. The corresponding T2 volumes were 120.8cm3, 29.1cm3 and 26.3cm3. The median T1 and T2 volume reductions were 77% (q1–3: 57–92%) and 78% (q1–3: 60–85%) at 13 months post-IMRT. Initial T2 volume was associated with worse RFS (p = 0.04) but not OS (p = 0.96). There was no association between median T2 volume reduction and RFS (p = 0.77).For patients assessable at year 4 post-IMRT, no late CTCAE Grade 3/4 toxicity events were recognised. 92% of patients were ECOG PS 0–1, 45% were employed at prior capacity and 28% were working with impairment. ConclusionPatients with large volume IDH-mutant Grade 3 glioma demonstrated significant tumour reduction post-IMRT, and good long-term outcomes with respect to survival and functional status. Although larger IMRT volumes were associated with poorer RFS, this was also associated with the initial volume of non-enhancing tumour.

Phase 2 Clinical Trial of Simultaneous Boost Intensity Modulated Radiation Therapy With 3 Dose Gradients in Patients With Stage I-II Nasal Type Natural Killer/T-Cell Lymphoma: Long-Term Outcomes of Survival and Quality of Life

The aim of this study was to investigate the treatment results and long-term quality of life in patients with early-stage extranodal natural killer/T-cell lymphoma who were prospectively treated with simultaneous boost intensity modulated radiation therapy (SIB-IMRT) with 3 dose gradients. Sixty patients with stage I-II nasal cavity natural killer/T-cell lymphoma (NKTCL) and Waldeyer's ring NKTCL were enrolled in a single-arm, prospective, phase 2 clinical trial from August 2011 to April 2015. All patients were treated with definitive radiation therapy combined with short-course induction chemotherapy. A newly designed SIB-IMRT scheme was uniformly adopted, with 54.6 Gy for the gross tumor volume (GTV) of the primary tumor and GTV of the positive lymph nodes, 50.7 Gy for the high-risk clinical target volume (CTV), and 45.5 Gy for the low-risk CTV, all delivered in 26 daily fractions. Before SIB-IMRT, L-asparaginase-based induction chemotherapy was used in 95.0% (57/60) of patients. With a median follow-up time of 95.8 months, the 5-year locoregional recurrence-free survival, progression-free survival, and overall survival rates were 83.3%, 81.7%, and 88.3%, respectively. Dosimetric analysis in the first 21 patients showed satisfying conformality for planning target volume of GTV, high-risk CTV, and low-risk CTV, while the organs at risk were well protected. The results of long-term quality-of-life investigations in patients without progression were favorable, and nasal discomfort was the most common symptom. No grade 3 or 4 acute or late toxicities were observed. The scheme of target volume delineation and dose setting that we designed has favorable clinical effects with mild side effects in treating patients with stage I-II nasal cavity NKTCL and Waldeyer's ring NKTCL.

Analysis of the prognostic factors of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in 220 cases of locally advanced squamous esophageal cancer: a retrospective cohort study.

Esophageal cancer is one of the most common malignant tumors in China. Patients with advanced esophageal cancer often cannot be treated by surgery; in these cases, radiation therapy is usually applied. However, there are currently few studies on the clinical efficacy of this treatment method. The present study aimed to investigate and observe the clinical efficacy and related prognostic factors of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in esophageal squamous carcinoma, and to provide a reference for clinicians in radiotherapy (RT) departments. The clinical and follow-up data of 220 patients with esophageal squamous carcinoma admitted to the First Affiliated Hospital of Bengbu Medical College from January 2017 to December 2018 were retrospectively analyzed to assess the relevant prognostic factors and analyze their effects on 3-year overall survival (OS) and progression-free survival (PFS). The prognostic influencing factors were analyzed using the log-rank test and Cox multi-factor regression analysis. The median follow-up time was 56.0 months (3.0 to 66.0 months). The 1-, 2-, and 3-year survival rates were 68.6%, 49.1%, and 36.3%, respectively, for the entire cohort, and the 1-, 2-, and 3-year PFS rates were 52.3%, 37.7%, and 25.5%, respectively. The median OS time was 24 months [95% confidence interval (CI): 19.16-28.84 months] and the median PFS time was 15 months (95% CI: 11.04-18.96 months). The multifactorial analysis results showed that gender, RT dose, treatment modality, absolute lymphocyte count (ALC), and gross tumor volume (GTV) were independent prognostic factors affecting 3-year OS (P<0.05); while gender, N-stage, RT dose, and GTV were independent prognostic factors affecting 3-year PFS (P<0.05). In the SIB-IMRT era, the survival of esophageal squamous cell carcinoma (ESCC) patients treated with radical (chemo)radiotherapy is relatively satisfactory. As a single-institution study on radiation therapy for esophageal cancer, this study yielded accurate results that help to provide references for subsequent related studies and clinicians' selection of treatment options.

A Prospective Analysis of Toxicity Associated with Intraoperative, Real-Time Planned Low Dose Rate Brachytherapy or Intensity-Modulated Radiotherapy Boost for High/Intermediate Risk Prostate Cancer

<h3>Purpose/Objective(s)</h3> The ASCENDE-RT trial which used pre-planned brachytherapy boost (BT) reported worse treatment-related morbidity with BT vs dose-escalated intensity-modulated radiotherapy boost (DE-IMRT) for prostate radiation therapy (RT). However, toxicity is technique dependent and the outcomes of real-time intraoperative BT have not been well studied. We evaluate the toxicity profile of intraoperative, real-time planned BT vs DE-IMRT. <h3>Materials/Methods</h3> 402 patients treated from 2010-18 at our institution were included. Median dose for DE-IMRT was 79Gy. BT included IMRT to a median of 45Gy plus BT boost of 110 Gy. Patient-reported outcomes using the validated Prostate Cancer Symptom Indices and physician-graded CTCAE toxicity were prospectively collected from baseline to 2yrs post-RT. Clinically meaningful symptoms were defined as ≥Grade 2. Per institutional practice, an α-1 blocker is started prior to BT but not DE-IMRT boost. We report acute (0-6 months) & late (1 & 2yr) toxicity. Multivariable logistic regression calculated odds ratios (OR) for symptoms & controlled for hormone therapy, image guidance modality, risk category & age. <h3>Results</h3> At acute, 1-, & 2-yr time points 148, 108, 54 & 254, 214, 162 patients were available for BT & DE-IMRT analysis, respectively. Baseline and acute genitourinary (GU) or gastrointestinal (GI) symptoms did not differ between cohorts. For both modalities, PRO GI and GU symptom prevalence peaked acutely, declined over 1yr and returned near baseline by 2yrs (Table). At 2yrs, a difference in ≥Grade 2 CTCAE GU toxicity persisted (19% vs 2%, p = <0.001); urinary frequency (6% vs 0%, p = 0.02), & incontinence (9% vs 2%, p = 0.02) differed most. On MVA, BT had higher 2-yr GU symptoms for PRO (OR 32.0, 95%CI: 6.2-165, p < 0.0001) & CTCAE (2.2, 1.4-3.6, p = 0.0006). Cumulative incidence of CTCAE ≥Grade 3 events at 2yr were GU 3.4% vs 0%, p = 0.007 & GI 2.0% vs 2.0%, p = 1.0 for BT & DE-IMRT. <h3>Conclusion</h3> This large single institution series with prospectively collected PRO & CTCAE toxicity is one of the first to report outcomes for intraoperatively, real-time planned BT. Odds of GU symptoms ≥Grade 2 are elevated with BT but cumulative incidence of GU/GI CTCAE ≥Grade 3 toxicity at 2yr was <4% for BT & DE-IMRT. Our results may assist in counseling and suggest that among appropriately selected patients a BT boost with intraoperative planning is reasonably well tolerated.

Comparison of Simultaneous Integrated Boost IMRT for Dose Escalation (54 Gy) and Conventional IMRT (45 Gy) Twice Daily Combined with Concurrent Chemotherapy for Limited-Stage Small-Cell Lung Cancer: Analysis of Two Prospective Trials

<h3>Purpose/Objective(s)</h3> Twice-daily thoracic radiotherapy (TRT) with concurrent chemotherapy is standard for limited-stage small-cell lung cancer (LS-SCLC). However, the importance of twice-daily simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) has not been clearly defined in LS-SCLC. Therefore, we conducted a prospective single arm, multicenter phase II study of SIB-IMRT for dose escalation (54 Gy) to the gross tumor volume for LS-SCLC. Here, we compared SIB-IMRT for dose escalation (54 Gy) to the gross tumor volume versus conventional intensity-modulated radiotherapy (IMRT) of standard-dose (45 Gy) twice-daily combined with concurrent chemotherapy in patients with LS-SCLC. <h3>Materials/Methods</h3> Sixty patients with LS-SCLC were entered from 2015 to 2021 in the phase II study of SIB-IMRT, and all 60 patients were treated with SIB-IMRT to the postchemotherapy tumor volume, as the SIB-IMRT group. In the SIB-IMRT group, the prescribed dose was 54Gy at 1.8 Gy twice daily to PGTV, and 45 Gy at 1.5 Gy twice daily to PCTV. We previously conducted a prospective phase III study on thoracic radiotherapy (TRT) target volumes for LS-SCLC (Cancer, 2020, 126(4), 840-849). In that study, from 2012-2017, 85 patients received thoracic IMRT to the postchemotherapy tumor volume, as the IMRT group. In the IMRT group, the prescribed dose was 45 Gy at 1.5 Gy per twice-daily fraction to both the planning gross tumor volume (PGTV) and the planning clinical tumor volume (PCTV). All of the 145 patients in both groups received concurrent chemoradiotherapy (CCRT) after completion of 2 cycles of induction cisplatin-etoposide chemotherapy, and received chemotherapy for 4 to 6 cycles in total. We compared progression free survival (PFS) and overall survival (OS) between the treatment groups by using the Kaplan-Meier method. <h3>Results</h3> Overall, with a median follow-up of 34.6 months, the median PFS and OS were 11.9 and 23.7 months, respectively. The patients in the SIB-IMRT group showed marginal longer PFS than those in the IMRT group (13.3 months versus 11.5 months; <i>p</i> = 0.08). The median OS of the SIB-IMRT and IMRT groups were 35.0 and 20.3 months, with the 2-year OS rate of 66.1% and 38.8%, respectively (<i>p</i> =0.007). For radiotherapy toxicity, grade 2 acute esophagitis was more common in the SIB-IMRT group, but grade≥3 esophagitis and grade≥2 pneumonitis was no difference in both two groups. <h3>Conclusion</h3> For LS-SCLC patients, SIB-IMRT for dose escalation (54 Gy at 1.8Gy twice daily) to PGTV benefited survival greatly. Our results suggest that SIR-IMRT is safe and effective for patients with LS-SCLC and should be further evaluated in a large prospective clinical trial.

SIB-IMRT combined with apatinib for unresectable hepatocellular carcinoma in patients with poor response to transarterial chemoembolization

Radiotherapy combined with apatinib exhibits synergistic anti-tumor effect, while the application of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) combined with apatinib in HCC patients is scarce. Hence, this study aimed to explore the treatment response, survival, and safety profile of the SIB-IMRT combined with apatinib in unresectable HCC (uHCC) patients. A total of 19 uHCC patients with deficient response to transarterial chemoembolization (TACE), who scheduled for SIB-IMRT combined with apatinib treatment were enrolled. The SIB-IMRT was applied at the following dose: 95% planning target volume (PTV) at 30-50Gy/2-2.5Gy/15-20f and 90% Boost of 45-72Gy/3-4.5Gy/15-20f at 5 times per week with cone beam computerized tomography validation. During and after radiotherapy, the apatinib was administrated orally with the initial dose of 500mg per day. The complete response, partial response, stable disease, and progressive disease rates were 31.6%, 36.8%, 21.1% and 10.5%, respectively. Consequently, the objective response rate and disease control rate were 68.4% and 89.5%, respectively. During a median follow-up duration of 9.0 months, the median progression-free survival (PFS) was 6.0 (95% confidential interval (CI): 4.9-7.1) months with 1-year PFS rate of 42.1%; the median overall survival (OS) was not reached with 1-year OS rate of 54.6%. The safety profile was acceptable with the most common adverse events including myelosuppression (42.1%), skin reaction (36.8%), and albuminuria (26.3%). SIB-IMRT combined with apatinib exhibits a good efficacy and tolerable safety profile, which could be considered as a potential treatment choice for uHCC patients who have deficient response to TACE.

Clinical Implication of Simultaneous Intensity-modulated Radiotherapy Boost to Tumor Bed for Cervical Cancer with Full-thickness Stromal Invasion.

ObjectiveThe objective of this study was to retrospectively explore the clinical implications of simultaneous intensity-modulated radiotherapy (IMRT) boost to the tumor bed in cervical cancer with full-thickness stromal invasion (FTSI).Patients and MethodsPatients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB and IIA cervical cancer with confirmed FTSI were included. Patients received pelvic IMRT from a dose of 50.4 Gy in 28 fractions with (or without) a simultaneous integrated boost (SIB) to 58.8 Gy in 28 fractions for the tumor bed. The progression-free survival (PFS), overall survival (OS), and pelvic-PFS (p-PFS) were analyzed using the Kaplan–Meier method, and independent prognostic factors were explored by Cox regression analyses.ResultsPatients without a tumor bed boost had a poor prognosis. The 5-year OS was 81.3% versus 58.3% and the 5-year PFS rates were 75.0% versus 57.6% (boost vs non-boost). The FIGO stage, pathology, adjuvant chemotherapy, and tumor bed boost were independent factors affecting both the 5-year OS and PFS. Subgroup analysis showed that the SIB group had a higher 5-year OS, PFS, and p-PFS for different stages, lymph node status, and risk groups than the non-SIB group. Recurrence occurred in 268 of 910 (29.5%) patients without SIB and 49 of 293 (16.7%) with SIB. Among patients with recurrence, 113 of 282 (40.1%) in the non-boost group compared with 14 of 51 (23.0%) patients in the boost group had a pelvic recurrence. Tumor bed boost resulted in an increase in the mean radiation dose to the intestine, rectum, and bladder, although there were no differences in the rates of acute and late toxicities between the 2 groups.ConclusionTumor bed boost by external beam radiotherapy (EBRT) is an effective and safe method for patients with FTSI and risk factors. Compared with the standard prophylactic radiation, tumor bed boost by EBRT was not associated with increased acute and late toxicities.

Twice-Daily Thoracic Radiotherapy by Intensity-Modulated Radiation Therapy (IMRT) or Simultaneous Integrated Boost (SIB) IMRT With Concurrent Chemotherapy for Limited-Stage Small Cell Lung Cancer Patients? A Propensity-Score Matched Analysis

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy is the standard treatment for limited-stage small-cell lung cancer patients (SCLC), but the optimal dose and schedule of radiotherapy have not been established. <h3>Materials/Methods</h3> We retrospectively reviewed the clinical records of limited-stage SCLC patients treated with twice-daily thoracic radiotherapy by intensity modulated radiotherapy (IMRT) or Simultaneous integrated boost IMRT (SIB-IMRT) with concurrent chemotherapy between December 2009 to December 2017. The patients were divided into two groups according to the radiotherapy dose. The patients of SIB-IMRT group received 57Gy at 1.9Gy twice-daily to the gross tumor volume (GTV), 51Gy at 1.7Gy twice-daily to the clinical target volume (CTV) and 45Gy at 1.5Gy twice-daily to the planning target volume (PTV), and the patients of IMRT group received 45Gy at 1.5Gy twice-daily to PTV. A 1:1 propensity score matching (PSM) was applied to balance observable potential confounding factors between two groups. Primary endpoint was progression-free survival (PFS). Overall survival (OS), objective tumor response (ORR) and treatment-related toxicities were also evaluated. Statistical analyses were conducted using SPSS version 22.0 and statistical significance was defined as <b>P</b> < 0.05. <h3>Results</h3> A total of 112 patients were enrolled in our study, including 71 patients in IMRT group and 41 patients in SIB-IMRT group. After PSM, the clinical features were well balanced between two groups included 37 patients each. ORR in IMRT group and SIB-IMRT group were 94.6% (35/37) and 97.3% (36/37), respectively. Median PFS was 17.54 months in IMRT group <b>vs</b> 34.92 months in SIB-IMRT group (<b>P</b> = 0.047). Median OS was 38.52 months in IMRT group <b>vs</b> 63.41 months in SIB-IMRT group (<b>P</b> = 0.261). The incidence of grade 3-4 treatment-related toxicities was 43.24% (32/74), and there was no significant difference between two groups (<b>P</b> = 0.639). <h3>Conclusion</h3> Compared with IMRT, the high dose of twice-daily thoracic radiotherapy by SIB-IMRT approach with concurrent chemotherapy for the patients with limited-stage SCLC were well-tolerated and may improve PFS, but PFS improvement didn't result in significant advantage in OS.

The feasibility of a dose painting procedure to treat prostate cancer based on mpMR images and hierarchical clustering

BackgroundWe aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique.MethodsThe mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures.ResultsAll the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value < 0.001) from those of the IMRT. However, the whole prostate ADC and prostate-specific antigen (PSA) indicated no significant difference (p-value > 0.05) between the DP versus IMRT.ConclusionsThe results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients’ dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer.Trial registration: IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019, https://en.irct.ir/trial/34305.

The promising outcome with simultaneous integrated boost intensity modulated radiotherapy in confined nasal extranodal NK/T-cell lymphoma

The study aimed to retrospectively analyze the prognosis of patients with stage IE nasal extranodal natural killer/T-cell lymphoma (ENKTL) with dose reduction to clinical target volume (CTV) by using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT). Forty-four patients were reviewed retrospectively. The prescribed dose was 45 Gy/25 fractions for extended involved-field site and 50–55 Gy/25 fractions for primary tumor site by using SIB-IMRT. The 5-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81.2%, 93.0%, and 78.8%, respectively. The complete response (CR) rate was 85.4% (37/44). Three patients (6.8%) patients had local failure and 3 (6.8%) patients developed systemic failure. There was only one patient had grade 3 mucositis and 2 patients had grade 3 or grade 4 hematologic toxicities. For patients with stage IE nasal ENKTL, appropriate dose reduction to CTV by SIB-IMRT strategy is feasible and safe with a promising outcome.

Interim analysis of a phase II study of simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) in combination with 5-FU and mitomycin-C among patients with locally advanced anal canal cancer.

e15501 Background: Concomitant radiochemotherapy is the standard treatment of locally advanced epidermoid anal canal carcinoma (EACC) but conventional radiotherapy (RT) frequently induces significant non-hematological toxicities, resulting in long treatment breaks. Given the numerous anatomic pelvic structures, EACC has become of interest for Intensity-Modulated Radiation Therapy (IMRT) despite the induced cutaneous toxicities responsible for RT breaks. Given the deleterious effect of treatment duration on local control and survival in other epidermoid cancers, continuous IMRT is challenging to control EACC. Several SIB-IMRT schedules provided similar results with moderate doses and schedules delivering higher doses with short breaks. Yet, standard SIB-IMRT schedule in EACC still not exists. We propose to concomitantly assess the safety and efficacy of continuous SIB-IMRT without planned breaks and concurrent chemotherapy (CT) to improve the treatment of locally advanced EACC by reducing the proportion of patients (pts) requiring RT breaks for toxicities. Methods: The CANAL-IMRT-01 phase 2 trial (NCT02701088) targets pts with histologically proven EACC candidate for concomitant RT of pelvic and inguinal nodes plus CT. Applying a two-step Bryant &amp; Day design, the main criterion is based on both efficacy and safety. Efficacy is defined as the proportion of pts alive with no local disease progression 3 months after the end of IMRT; safety is defined as the proportion of pts with no RT breaks required by grade ≥3 toxicities. Assuming the unacceptable and acceptable proportions of pts without toxicity requiring IMRT break are 60 and 80% respectively, the unacceptable and acceptable 3-month-progression-free-survival are 80 and 90%, 14 assessable pts at first step and 46 in the second are required (alpha risk 5%, 90% power). To anticipate a 10% drop out rate, 16 pts were needed in first step, with ≥11 objective local responses and ≤6 toxicity-induced IMRT breaks to pursue. Treatment consists in 50 days of concomitant CT (2 cycles of 5FU and Mitomycin-C) and SIB-IMRT delivered by helical tomotherapy: 61.2Gy/1.7Gy to the primary tumor, 57.6Gy/1.6Gy to involved nodes, and 54/1.5Gy to elective pelvic lymph nodes. Results: From December 2015 to June 2017, 16 pts were enrolled: 11 female (73%), median age 62 [55-66]. 15 pts were assessable for efficacy and safety. All 15 pts had a 3-month locoregional response (12 complete responses, 3 partial responses). SIB-IMRT breaks were required by toxicities for 4 out of 15 pts: G1 radiodermitis, G2 inguinal and epithelitis, G1 fever, G3 anorexia and vertigo. Conclusions: The planned interim analysis of continuous SIB-IMRT plus CT allowed pursuing this phase 2 trial to assess the relevance of such schedule for locally advanced ASCC. Enrolment is still ongoing. Clinical trial information: NCT02701088.

Effect of Simultaneous Integrated Boost Intensity Modulated Radiation Therapy (SIB-IMRT) and Non-Operative Strategy on Outcomes of Distal Rectal Cancer Patients with Clinically Positive Lateral Pelvic Lymph Node.

BackgroundWe aimed to analyze the effect of simultaneous integrated boost intensity modulated radiation therapy (SIB-IMRT) and non-operative treatment on the clinical outcomes of distal rectal cancer patients exhibiting clinically positive lateral pelvic lymph nodes (LPLNs).MethodsWe reviewed the medical records of patients diagnosed as having distal rectal adenocarcinoma with clinically positive LPLNs (≥7 mm, with irregular borders or mixed signal intensity) using primary pelvic magnetic resonance imaging (MRI). These patients had received SIB-IMRT-based neoadjuvant chemoradiotherapy (NCRT) and non-operative treatment according to the heterogeneity of the disease or personal preference. Chi-square tests were used to compare data between the two groups. Progression-free survival (PFS) and local regrowth were evaluated using the Kaplan-Meier method.ResultsBetween 2016 and 2019, we analyzed 75 patients diagnosed as having clinically positive LPLNs using primary MRI. SIB-IMRT was delivered to the planning positive LPLNs (PGTVn) at a total dose of 56–60 Gy. After NCRT, 23 patients underwent non-operative treatment. Among these patients, the median short axis of LPLNs was 8 mm (range: 7–21 mm). Fifteen patients were categorized into the mesorectal fascia (MRF)-positive group. The median follow-up duration for these patients was 19.8 months, and no patient exhibited LPLN regrowth. The 2-year PFS rate was 85.6% for non-operative patients, 74.6% for operative patients, and 90.0% for the pathological complete response (pCR) subgroup. Eighteen patients who underwent non-operative treatment were included in the clinical complete response (cCR) subgroup. The 2-year PFS and local regrowth rates in this group were similar to those in patients with clinically negative LPLN who achieved cCR. During NCRT, 21 (28.0%) patients experienced grade 2–3 acute reversible toxicity.ConclusionsSIB-IMRT could eliminate metastases in LPLNs in a safe and effective manner, and non-operative strategies may be promising for cCR patients.

Toxicity of Simultaneous Integrated Boost Intensity Modulated Radiation Therapy in Post-Operative Oral Cavity Cancer

To assess the acute toxicity of Simultaneous integrated boost intensity modulated radiation therapy (SIB-IMRT) in postoperative oral cavity cancers with intermediate risk features was the primary objective of this study. The secondary objectives were to assess late toxicity and efficacy. This was a prospective, interventional study conducted at a single center. Patient accrual was done from November 2017 to August 2018 and data was analyzed in November 2019. Patients of oral cavity carcinoma who underwent surgery and had at least one risk factor on histopathological evaluation i.e., T3/T4 stage, node positive without extra capsular extension, lymphovascular invasion (LVI), perineural invasion (PNI), close margin (<5 mm), depth of invasion ≥3 mm for tongue and ≥7 mm for buccal mucosa were included. All patients had indication for adjuvant RT alone without concurrent chemotherapy. Post-operative RT was delivered with SIB-IMRT technique using 6 MV X-rays on a Linear accelerator. A dose of 63.6 Gray (Gy) in 30 fractions was delivered to high risk clinical target volume (CTV), 54 Gy in 30 fractions to intermediate risk CTV and 51 Gy in 30 fractions to low risk CTV. Dose constraints for the spinal cord was Dmax ≤ 42Gy, PRV cord Dmax ≤ 48Gy, brainstem Dmax ≤50.4 Gy, each parotid Dmean ≤ 26 Gy. Weekly assessment was done during RT and acute radiation toxicities were recorded as per Radiation Therapy Oncology Group (RTOG) acute toxicity criteria in terms of oral mucositis (OM), skin toxicity and dysphagia. Subsequent visits were monthly for the first 3 months, 2 monthly for the next 6 months and 3 monthly thereafter. Clinical examination with an assessment of the late toxicity was done as per RTOG late morbidity scoring schema. Radiological imaging (CECT or MRI) was done at 3 months post RT. Statistical analysis was performed using statistical package for sciences (SPSS version 20.0). Survival analysis was done by Kaplan-Meier method with log rank test. A total of 30 patients were included in the study with a median age of 48.5 years (range 33-75 year). The frequency N (%) of primary site involved was tongue 13(43.33), buccal mucosa 12(40), alveolus 4 (13.33) and retromolar trigone 1 (3.33). All patients completed RT and the median duration of RT was 42 days [mean days 42.3±0.93]. Maximum acute grade ≤2 vs grade 3 oral mucositis was 46.67% vs 53.33%, skin toxicity was 86.67% vs 13.33 %, dysphagia was 66.67% vs 33.33% respectively. No patients had grade 4 or 5 acute toxicity. At a median follow up of 11 months [range 6-18 month], grade 1 late toxicities were 53.33% (subcutaneous toxicity) and 33.33% (xerostomia). Loco regional control was 96.67%. IMRT-SIB is safe in terms of acute toxicity however the short follow up duration limits assessment of late toxicity and locoregional control rates in post-operative oral cavity cancers with intermediate risk.Abstract 3966; TableRisk factor for adjuvant RTN (%)>pT316(53.33)p N+9(30)PNI+11(36.67)LVI+5(16.67)Close margin1(3.33)DOI20(66.67) Open table in a new tab

P-341 Capecitabine/mitomycin versus 5-fluorouracil/mitomycin in combination with simultaneous integrated boost-intensity modulated radiation therapy for anal cancer

Within the past decade, several studies have tested capecitabin as a substitute for 5-FU in the treatment of localised squamous cell carcinoma of the anal canal (SCCAC) and reported similar clinical response rates, making capecitabin an acceptable and more convenient alternative to infusional 5-FU. However, the differences in efficacy between capecitabine and 5-FU in CRT with simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) for locally SCCAC are not documented. We performed this retrospective study to compare the response of capecitabine and 5-FU in survival and toxicity terms in patients with locally SCCAC treated with concurrent SIB-IMRT.

Dose escalation in radiotherapy for incomplete transarterial chemoembolization of hepatocellular carcinoma.

To investigate the efficacy of radiation dose escalation in patients with hepatocellular carcinoma (HCC) after incomplete transarterial chemoembolization (TACE). This study evaluated retrospective data of 323 HCC patients who received radiotherapy after incomplete TACE from 2001-2016. Radiation dose in biologically effective dose (BED) (α/β = 10) was categorized as <72 Gy (261 patients) and ≥72 Gy (62patients). Simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) was used significantly more frequently in the high-dose group (64.5% vs. 12.9%; P < 0.001). Local failure-free rate (LFFR), progression-free rate (PFR), and toxicities were compared between the two groups. Additionally, propensity score matching was performed. Median follow-up time for patients who were alive at the time of analysis was 47months (range 18-189months). Median overall survival after radiotherapy was 14months. In multivariate analysis, BED ≥72 Gy was an independent predictor of favorable LFFR (hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.14-0.72; P = 0.006) and PFR (HR 0.67; 95% CI 0.45-0.98; P = 0.04). In the propensity score-matched cohort (62pairs), 1‑year LFFR (94% vs. 81%; P = 0.002), and 1‑year PFR (49% vs. 42%; P = 0.01) were significantly higher in the high-dose group. Treatment-related toxicities were comparable between the high-dose and low-dose groups (classic radiation-induced liver disease: 5.3% [3/57] vs. 13.8% [29/210], P = 0.08; grade2-4 gastrointestinal bleeding: 3.2% [2/62] vs. 7.3% [19/261], P = 0.39). Radiation dose with BED ≥72 Gy improved LFFR and PFR without increasing toxicity. In radiotherapy for incomplete TACE of HCC, dose escalation using SIB-IMRT should be actively considered to improve oncologic outcome.

Definitive, intensity modulated tomotherapy with a simultaneous integrated boost for prostate cancer patients - Long term data on toxicity and biochemical control.

To report long-term data regarding biochemical control and late toxicity of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) with tomotherapy in patients with localized prostate cancer. Dose escalation improves cancer control after curative intended radiation therapy (RT) to patients with localized prostate cancer, without increasing toxicity, if IMRT is used. In this retrospective analysis, we evaluated long-term toxicity and biochemical control of the first 40 patients with intermediate risk prostate cancer receiving SIB-IMRT. Primary target volume (PTV) 1 including the prostate and proximal third of the seminal vesicles with safety margins was treated with 70Gy in 35 fractions. PTV 2 containing the prostate with smaller safety margins was treated as SIB to a total dose of 76Gy with 2.17Gy per fraction. Toxicity was evaluated using an adapted CTCAE-Score (Version 3). Median follow-up of living patients was 66 (20-78) months. No late genitourinary toxicity higher than grade 2 has been reported. Grade 2 genitourinary toxicity rates decreased from 58% at the end of the treatment to 10% at 60 months. Late gastrointestinal (GI) toxicity was also moderate, though the prescribed PTV Dose of 76Gy was accepted at the anterior rectal wall. 74% of patients reported any GI toxicity during follow up and no toxicity rates higher than grade 2 were observed. Grade 2 side effects were reported by 13% of the patients at 60 months. 5-year freedom from biochemical failure was 95% at our last follow up. SIB-IMRT using daily MV-CT guidance showed excellent long-term biochemical control and low toxicity rates.

P205 - Cosmetic result and safety in synchronous bilateral breast cancer (SBBC) patients treated with hypofractionated simultaneous integrated boost intensity modulated radiotherapy (HF-SIB-IMRT)

P205 - Cosmetic result and safety in synchronous bilateral breast cancer (SBBC) patients treated with hypofractionated simultaneous integrated boost intensity modulated radiotherapy (HF-SIB-IMRT)

Randomized controlled study comparing simultaneous modulated accelerated radiotherapy versus simultaneous integrated boost intensity modulated radiotherapy in the treatment of locally advanced head and neck cancer

ObjectivesComparison of two fractionation schedules of intensity modulated radiotherapy (IMRT) for locally advanced head and neck cancer – simultaneous integrated boost (SIB-IMRT) and simultaneous modulated accelerated radiotherapy (SMART) boost in terms of toxicity and survival end-point measures. Patients and methodsSixty patients with locally advanced head and neck cancer were randomized in two treatment arms (SIB-IMRT [control arm] and SMART boost arm [study arm]). In the control arm, patients received 70, 63 and 56 Gy in 35 fractions to clinical target volumes (CTV) 1, 2 and 3, respectively. In the study arm, patients received 60 and 50 Gy to CTV 1 and CTV 3, respectively. Toxicities, progression free survival (PFS) and overall survival (OS) were compared between both arms. ResultsBaseline patient-related characteristics were comparable between the arms except for primary site of tumour. No significant differences were noted in acute toxicities between the arms except for fatigue which was statistically higher for control arm. No significant differences in 2-year late toxicities were observed. The median follow-up duration was 25.5 (range, 1.8–39.9) months. The 2-year PFS was 53.3% and 80.0% (p = 0.028) for control and study arm, respectively. The 2-year OS was 60.0% and 86.7% (p = 0.020) in control and study arms, respectively. Multivariate analysis showed clinical stage and site to be significant predictors for OS and PFS, respectively. ConclusionsThe SMART boost technique can be a feasible alternative fractionation schedule that reduces the overall treatment time, maintaining comparable toxicity and survival compared with SIB-IMRT.