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Abstract 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.

Abstract 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.

• RT margins and doses for high-risk neuroblastoma vary across studies. • Highly-conformal IGRT with reduced margins and boost on residue ≥ 1 cm3 was applied. • 5-years LRF rate of 7.8 % was excellent and comparable for residue < 1 cm3 vs. ≥ 1 cm3. • LRF was observed in 6/77 patients of whom only 2 had an isolated failure. • Residual activity on nuclear- and MRI[DWI]-scans was not predictive for LRF. 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. 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 cm3 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 cm3 vs. ≥ 1 cm3 (with/without locoregional activity on nuclear- and MRI[diffusion-weighted imaging]-scans) pre-radiotherapy, age at diagnosis, MYCN-status, [131I]mIBG therapy, response to induction chemotherapy, interval to radiotherapy onset, and metastatic site irradiation. Among the 77 included patients, 34 had residual lesions (median volume: 10.0 cm3, 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 cm3 vs. ≥ 1 cm3 (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. In HR-NBL, IGRT with reduced margins and a boost dose for residual lesions ≥ 1 cm3 demonstrated excellent locoregional control, comparable to modern literature. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fei Lu,1,2 Yu Hou,1 Yaoxiong Xia,1 Lan Li,1 Li Wang,1 Ke Cao,1 Haixia Chen,1 Li Chang,1 Wenhui Li11Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 2Department of Oncology and Hematology, The First People’s Hospital of Honghe State, Mengzi, Yunnan, People’s Republic of ChinaPurpose: 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.Keywords: non-small-cell lung carcinoma, brain metastases, brain radiotherapy, radiotherapy boost, tyrosine kinase inhibitor

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. [ABSTRACT FROM AUTHOR]

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. 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 I2 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. 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). 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. [ABSTRACT FROM AUTHOR]

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Abstract: 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. 10Gy boost was prescribed in case of FMS>5mm; 16Gy boost with FMS between 2 and 5mm; 20Gy boost in case of FMS<2mm or positive. Results: After a median follow up of 5.2years, 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 &y& Elsevier]

Purpose: (1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. Methods and Materials: Subjects were 2,264 women with pT1–3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast ± boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer–specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. Results: Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age <45 years, 11.8% with Grade III, 11.3% with lymphovascular invasion (LVI), and 26.3% with ≥4 positive nodes. Corresponding rates in the negative margin cohort were 2.3%, 2.4%, 1.0%, and 2.4%, respectively. On Cox regression analysis of the entire cohort, close or positive margin, Grade III histology, ≥4 positive nodes, and lack of systemic therapy were significantly associated with higher LR risk. When close/positive margin cases were matched to negative margin controls, the difference in 5-year LR remained significant (4.25% vs. 0.7%, p < 0.001). Conclusions: On univariable analysis, subsets with close or positive margins, in combination with age <45 years, Grade III, LVI, and ≥4 positive nodes, have 5-year LR >10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery. [ABSTRACT FROM AUTHOR]