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Introduction: Radiotherapy protocols for high-risk neuroblastoma (HR-NBL) vary across international studies. The purpose of this study was to evaluate the locoregional control in a national HR-NBL cohort treated with highly-conformal image-guided radiotherapy (IGRT), using reduced margins, and a boost dose for residual lesions., Materials and Methods: Patients treated with radiotherapy as part of first-line HR-NBL treatment between 2015 and 2022 were eligible. To obtain clinical, internal, and planning target volumes, +0.5 cm, 4DCT-based, and + 0.3/0.5 cm margins, respectively, were added to the edited gross tumour volumes. Prescription dose was 21.6/1.8 Gy, followed by 14.4/1.8 Gy for any residual lesions measuring ≥ 1 cm 3 at the time of radiotherapy planning. Intensity-modulated arc therapy was combined with daily cone beam CT-based online patient position verification. Locoregional failure (LRF) rates were compared for the presence of residual lesions < 1 cm 3 vs. ≥ 1 cm 3 (with/without locoregional activity on nuclear- and MRI[diffusion-weighted imaging]-scans) pre-radiotherapy, age at diagnosis, MYCN-status, [ 131 I]mIBG therapy, response to induction chemotherapy, interval to radiotherapy onset, and metastatic site irradiation., Results: Among the 77 included patients, 34 had residual lesions (median volume: 10.0 cm 3 , IQR 4.8-29.9) with activity visible on 17 nuclear- and 10 MRI-scans. Five-year LRF rate was 7.8 % (95 % confidence interval 1.8-13.8), and not significantly different between those with residual lesions < 1 cm 3 vs. ≥ 1 cm 3 (6.4 % vs. 14.3 %, respectively, p = 0.27), or any of the other variables. All 6 LRFs (2 isolated, 4 combined) occurred < 1.5 years post-radiotherapy., Conclusion: In HR-NBL, IGRT with reduced margins and a boost dose for residual lesions ≥ 1 cm 3 demonstrated excellent locoregional control, comparable to modern literature., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Atia Samim, Annemieke S. Littooij, Max Peters, Bart de Keizer, Alida F.W. van der Steeg, Raquel Dávila Fajardo, Kathelijne C.J.M. Kraal, Miranda P. Dierselhuis, Natasha K.A. van Eijkelenburg, Martine van Grotel, Roel Polak, Cornelis P. van de Ven, Marc H.W.A. Wijnen, Enrica Seravalli, Mirjam E. Willemsen-Bosman, Max M. van Noesel, Godelieve A.M. Tytgat, Geert O. Janssens: No conflict of interest]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis., Methods and Materials: Patients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments., Results: From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group., Conclusion: Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned., (© 2022. The Author(s).)

Purpose: Stereotactic radiosurgery (SRS) has become a standard approach for the treatment of patients with few metastatic brain lesions. However, the optimal treatment approach for the use radiotherapy in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) remain unclear. This study aimed to compare the survival outcomes and intracranial local control in NSCLC patients with 1-4 BMs who are treated with SRS using linear accelerators (LINAC-SRS), whole-brain radiotherapy (WBRT), or WBRT plus radiotherapy boost (WBRT + RTB)., Materials and Methods: We retrospectively analyzed 156 NSCLC patients with 1-4 BMs who received LINAC-SRS, WBRT, and WBRT + RTB. The median overall survival (OS), intracranial progression-free survival (iPFS), and distant brain failure-free survival (DBF-FS) and related prognostic factors were analyzed., Results: The median follow-up period was 31.6 months. The median OS times in the LINAC-SRS, WBRT, and WBRT + RTB groups were not reached, 33.3 months and 27.9 months, respectively. The difference in survival rate was non-significant (P = 0.909). The 2-year iPFS and DBF-FS rates in the LINAC-SRS, WBRT and WBRT + RTB groups were 51.6% and 37.5%; 42.0% and 50.4%; and 51.1% and 56.1%, respectively. There was no significant difference in 2-year iPFS or DBF-FS among the three groups (P = 0.572 for iPFS, P = 0.628 for DBF-FS). Multivariate analysis showed that the independent adverse prognostic factors for OS, iPFS, and DBF-FS were neurological symptoms, recursive partitioning analysis (RPA) class, and targeted therapy., Conclusion: LINAC-SRS did not result in significantly superior survival times or intracranial local control compared to WBRT or WBRT + RTB in the treatment of NSCLC patients with 1-4 BMs., (© 2022. The Author(s).)

Purpose: To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints., Materials and Methods: Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30 Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up., Results: Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20 Gy in 5 fr (N: 6; 19.4%), 20 Gy in 4 fr (N: 5; 16.2%), 25 Gy in 5 fr (N: 18; 58.0%) and 30 Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19 months (range 1-156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28 months; range 2-139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18 months (range 1-139). The 2-year OS after HRB was 57.4%, while 2-year OS from diagnosis was 77.3%., Conclusion: Treatment intensification with hypofractionated radiotherapy boost is well tolerated in pts affected by unresectable LAPC previously treated with CT/CRT. Its rates of local and pain control are encouraging, supporting its introduction in clinical practice. Timing, schedule and dose of HRB need to be further investigated to personalize therapy and optimize clinical advantages.

Aims: Improving pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy for locally advanced rectal cancer may facilitate surgery-sparing treatment paradigms. Radiotherapy boost has been linked to higher rates of pCR; however, outcomes in moderately escalated inverse-planning studies have not been systematically evaluated. We therefore carried out a systematic review and meta-analysis of radiation dose-escalation studies in the context of neoadjuvant therapy for locally advanced rectal cancer., Materials and Methods: A systematic search of Pubmed, EMBASE and Cochrane databases for synonyms of 'rectal cancer', 'radiotherapy' and 'boost' was carried out. Studies were screened for radiotherapy prescription >54 Gy. Prespecified quality assessment was carried out for meta-analysis inclusion suitability. Pooled estimates of pCR, acute toxicity (grade ≥3) and R0 resection rates were determined with random-effects restricted maximum-likelihood estimation. Heterogeneity was assessed with Higgins I 2 and Cochran Q statistic. Subset analysis examined outcomes in modern inverse-planning studies. Meta-regression with permutation correction was carried out for each outcome against radiation dose, radiotherapy technique, boost technique, chemotherapy intensification and other patient- and treatment-related cofactors., Results: Forty-nine primary and three follow-up publications were included in the systematic review. Pooled estimates of pCR, toxicity and R0 resection across 37 eligible publications (n = 1817 patients) were 24.1% (95% confidence interval 21.2-27.4%), 11.2% (95% confidence interval 7.2-17.0%) and 90.7% (95% confidence interval 87.9-93.8%). Within inverse-planning studies (17 publications, n = 959 patients), these rates were 25.7% (95% confidence interval 21.0-31.1%), 9.8% (95% confidence interval 4.6-19.7%) and 95.3% (95% confidence interval 91.6-97.4%). Regression analysis did not identify any significant predictor of pCR (P > 0.05)., Conclusions: Radiotherapy dose escalation above 54 Gy is associated with high rates of pCR and does not seem to increase the risk of acute grade ≥3 toxicity events. pCR rates approaching 25% may be achievable utilising moderate escalation (54-60 Gy) with modern inverse-planning techniques; however, a clear dose-response relationship was not identified in regression analysis and additional evidence is awaited given the prevalence of heterogenous single-arm studies to date., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: The addition of a postoperative tumour bed (cavity) boost after whole-breast radiotherapy (RT) is known to decrease the risk of local in-breast recurrence. The purpose of this retrospective study is to assess breast excision cavity changes and planned doses at the time of initial boost RT treatments after the completion of whole-breast RT., Methods: Over a 4-month period, women with highly visible cavity on computed tomography (CT) and treated with whole-breast RT followed by a conformal photon boost to the tumour bed were identified. The patient's day 1 boost online cone beam CT (CBCT) and corresponding setup corrections were overlaid with the planning CT image. The cavity and dose evaluation volumes (DEVs = 1 cm expansion of the cavity, excluding 5 mm of lung and skin) were assessed. Dosimetric evaluations were performed for maximum and minimum cavity doses, cavity volume receiving 90% (V90) and 95% (V95) of prescription dose, and DEV receiving 85% (V85), 95%, and 105% (V105) of the prescription dose. The two-tailed student t-test and Pearson's correlation test were performed for statistical analysis., Results: Eighteen patients were included in the analysis. The CT cavity (CAV CT ) volume (mean: 28.8 cc, SD 27.9) was larger than the CBCT cavity (CAV CBCT ) volume (mean: 21.1 cc, SD: 22.4) (P value= .003). The CT DEV similarly decreased at the time of boost; DEV CT (mean: 113.9 cc, SD: 63.2) versus DEV CBCT (mean: 92.3 cc, SD: 50.8), (P = .002). A strong correlation was observed between the initial CT cavity volume and cavity shrinkage observed at time of boost (day 1 CBCT) (Pearson's r = 0.697; r 2 = 0.486, P = .001). Both time periods from surgery to CT (median: 92 days, range: 31-227) and from surgery to day 1 CBCT (median: 141 days, range: 56-265) were not associated with cavity volume change. However, an inverse correlation was observed between time from initial CT to day 1 boost CBCT (median: 33 days, range: 24-54) and % cavity volume change (Pearson's r = -0.642; r 2 = 0.4121, P = .004). Dosimetric evaluations of the cavity and DEV showed no significant differences in maximum, minimum, and target dose coverage between the CT and boost volumes., Conclusion: In patients with breast cancer treated with a tumour bed boost after whole-breast RT, the postoperative cavity can shrink between the time of CT and day 1 boost. The extent of cavity reduction was greatest in patients with large postoperative cavities on initial CT. Despite the cavity size change, conformal boost fields provide adequate dose coverage to the cavity., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To compare the differences in survival and intracranial local control between patients treated with whole-brain radiotherapy (WBRT) and WBRT plus a radiotherapy boost (RTB) in non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). Patients and methods: Between May 2010 and October 2017, 206 NSCLC patients with BMs were treated with brain radiotherapy; among these patients, 140 patients underwent WBRT alone (group A) and 66 patients underwent WBRT plus RTB (group B). The endpoints included intracranial local progression-free survival and regional progression-free survival time (iLPFS and iRPFS, respectively) and overall survival (OS). Results: Between the two groups, not all baseline clinical factors were well-balanced. The median iLPFS was 17.9 months in group A and 22.3 months in group B. The 2-year iLPFS rates were significantly lower in group A than in group B (34.5% vs 49.3%, P =0.041); however, no significant differences were observed in OS or iRPFS. Multivariate analyses revealed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy was significantly associated with good OS, iLPFS, and iRPFS. Among the patients treated with TKIs (n=62), there were no differences in OS ( P =0.190), iLPFS ( P =0.334), or iRPFS ( P =0.338) between groups A and B. In the patients without TKI treatment (n=102), the median iLPFS was significantly longer in group B than in group A (16.7 vs 12.0 months, P =0.032), but no significant differences were found in OS ( p =0.182) or iRPFS ( P =0.837) between the two groups. Conclusion: WBRT plus RTB significantly improved iLPFS compared with WBRT alone, especially in patients without EGFR-TKI treatment. However,there were no significant differences in iRPFS or OS between the two groups. Patients treated with EGFR-TKIs may not benefit from WBRT plus RTB., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS)., Methods and Materials: A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive., Results: After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence., Conclusions: Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)