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Background This study aims to compare the therapeutic efficacy of whole brain radiotherapy (WBRT) versus WBRT plus simultaneous integrated boost (WBRT + SIB) in patients with brain metastases (BMs) from small cell lung cancer (SCLC). Methods A retrospective analysis was conducted on 127 patients with BMs from SCLC who received brain radiotherapy between 2014 and 2023 at the Cancer Hospital of the Chinese Academy of Medical Science. Among them, 71 patients underwent WBRT (25.0–54.0 Gy in 10–21 fractions), while 56 patients received WBRT + SIB (SIB to metastases: 18.0–60.0 Gy in 5–20 fractions). The overall survival (OS), intracranial progression-free survival (iPFS), objective response rate (ORR), and local control rate (LCR) were evaluated to assess the efficacy of the treatments. Results With a median follow-up of 14.9 months, the median OS was significantly longer in the WBRT + SIB group compared to the WBRT group (18.0 vs. 11.7 months). Similarly, the iPFS was extended in the WBRT + SIB group (12.2 vs. 7.6 months). Kaplan-Meier analysis revealed that WBRT + SIB significantly improved OS in patients with SCLC of BMs ( P  = 0.009). Subgroup analysis indicated that male patients, age < 60 years old, and multiple intracranial metastases benefited more from WBRT + SIB. Interaction tests suggested that age significantly influence the efficacy of WBRT + SIB, with patients < 60 years old deriving more benefit ( P  = 0.049). Concurrent WBRT + SIB with anti-angiogenic targeted therapy significantly improved iPFS ( P  < 0.001). Conclusions WBRT + SIB can prolong the OS in SCLC patients with BMs, with younger age and those receiving anti-angiogenesis therapy potentially achieving additional survival benefits.

Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.

Background: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. Methods: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). Results: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were −55.8% (±24.0%) and −52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). Conclusions: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

A systematic review of the published literature was conducted to analyze the management evolution of brain metastases from different cancers. Using the keywords “brain metastasis”, “brain metastases”, “CNS metastasis”, “CNS metastases”, “phase III” AND/OR “Randomized Controlled Trial” (RCT), relevant articles were searched for on the SCOPUS database. A total of 1986 articles were retrieved, published over a 45-year period (1977–2022). Relevant articles were defined as clinical studies describing the treatment or prevention of brain metastases from any cancer. Articles on imaging, quality of life, cognitive impairment after treatment, or primary brain tumors were excluded. After a secondary analysis, reviewing the abstracts and/or full texts, 724 articles were found to be relevant. Publications significantly increased in the last 10 years. A total of 252 articles (34.8%) were published in 12 core journals, receiving 50% of the citations. The number of publications in Frontiers in Oncology, BMC Cancer, and Radiotherapy and Oncology have increased considerably over the last few years. There were 111 randomized controlled trials, 128 review articles, and 63 meta-analyses. Most randomized trials reported on brain metastases management from unselected tumors (49), lung cancer (47), or breast cancer (11). In the last 5 years (2017 to 2022), management of brain metastasis has moved on from WBRT, the use of chemotherapy, and radio-sensitization to three directions. First, Radiosurgery or Radiotherapy (SRS/SRT), or hippocampal-sparing WBRT is employed to reduce radiation toxicity. Second, it has moved to the use of novel agents, such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) and third, to the use of molecularly directed therapy such as TKIs, in asymptomatic low volume metastasis, obviating the need for WBRT.

Background In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. Methods This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60–65 Gy in 25–28 fractions to primary lesions and positive lymph nodes; 50–50.4 Gy in 25–28 fractions to the pelvis) or intensity-modulated radiotherapy (50–50.4 Gy in 25–28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. Discussion Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. Trial registration The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

Introduction Aimed to develop a simple and robust volumetric modulated arc radiotherapy (VMAT) solution for comprehensive lymph node (CLN) breast cancer without increase in low‐dose wash. Methods Forty CLN‐breast patient data sets were utilised to develop a knowledge‐based planning (KBP) VMAT model, which limits low‐dose wash using iterative learning and base‐tangential methods as benchmark. Another twenty data sets were employed to validate the model comparing KBP‐generated ipsilateral VMAT (ipsi‐VMAT) plans against the benchmarked hybrid (h)‐VMAT (departmental standard) and bowtie‐VMAT (published best practice) methods. Planning target volume (PTV), conformity/homogeneity index (CI/HI), organ‐at‐risk (OAR), remaining‐volume‐at‐risk (RVR) and blinded radiation oncologist (RO) plan preference were evaluated. Results Ipsi‐ and bowtie‐VMAT plans were dosimetrically equivalent, achieving greater nodal target coverage (P < 0.05) compared to h‐VMAT with minor reduction in breast coverage. CI was enhanced for a small reduction in breast HI with improved dose sparing to ipsilateral‐lung and humeral head (P < 0.05) at immaterial expense to spinal cord. Significantly, low‐dose wash to OARs and RVR were comparable between all plan types demonstrating a simple VMAT class solution robust to patient‐specific anatomic variation can be applied to CLN breast without need for complex beam modification (hybrid plans, avoidance sectors or other). This result was supported by blinded RO review. Conclusions A simple and robust ipsilateral VMAT class solution for CLN breast generated using iterative KBP modelling can achieve clinically acceptable target coverage and OAR sparing without unwanted increase in low‐dose wash associated with increased second malignancy risk. Comprehensive lymph nodal (CLN) radiotherapy can improve the outcomes for advanced breast cancer patients, but it can be particularly challenging to balance target coverage and organ‐at‐risk sparing without complex beam modification (VMAT avoidance sectors, hybrid IMRT/VMAT fields, other) to limit the low‐dose wash and potential second malignancy risk. By presenting the first application of iterative learning to a knowledge‐based planning model in CLN‐breast radiotherapy, this study demonstrates that a simple and robust ipsilateral VMAT class solution can be applied without increase in low‐dose wash compared to benchmark base‐tangential IMRT/VMAT methods.

PurposeTo explore the feasibility and safety of simultaneous integrated boost technology (SIB) with elective nodal irradiation (ENI) to the cervical and upper mediastinal lymph node (LN) regions in upper thoracic esophageal squamous cell carcinoma (ESCC).Material and methodsPatients with pathologically proven unresectable upper thoracic ESCC were assigned 50.4 Gy/28 fractions (F) to the clinical target volume (encompassing the ENI area of cervical and upper mediastinal LN regions) and a boost of 63 Gy/28 F to the gross tumor volume. Chemotherapy consisted of courses of concurrent cisplatin (20 mg/m2) and docetaxel (20 mg/m2) weekly for 6 weeks. The primary endpoint was toxicity.ResultsBetween Jan 2017 and Dec 2019, 28 patients were included. The median follow-up time for all patients was 24.6 months (range 1.9–53.5). Radiation-related acute toxicity included esophagitis, pneumonia and radiodermatitis, all of which were well managed and reversed. Late morbidity included esophageal ulcer, stenosis, fistula and pulmonary fibrosis. Grade III esophageal stenosis and fistula was seen in 11% (3/28) and 14% (4/28) patients, respectively. The cumulative incidence rate of late esophageal toxicity was 7.7%, 19.2% and 24.6% at 6, 12 and 18 months, respectively. There was significant difference of the occurrence of severe late esophageal toxicity among the different volume levels of the esophagus, and cervical and upper mediastinal LNs which received ≥ 63 Gy stratified by the tertiles (p = 0.014).ConclusionsDespite the acceptably tolerated acute toxicity of SIB in concurrent CRT with ENI to the cervical and upper mediastinal LN regions for upper thoracic ESCC, the incidence of severe late esophageal toxicity was relatively high. Cautions are provided against easy clinical application of SIB (50.4 Gy/28F to the CTV, 63 Gy/28F to the GTV) in upper thoracic ESCC. Further exploration on dose optimization is warranted.

Purpose: We report the outcome of a mono-institutional retrospective study of sinonasal carcinoma with the primary focus on GTV (gross tumor volume) and the effect of radiotherapy. Methods: 53 patients with sinonasal carcinoma and that of the nasal cavity, paranasal sinus or both except lymphoma were included. All patients were treated between 1999 and 2017. For tumor volume delineation, all pre-therapeutic images were fused to the planning CT (computed tomography). Results: The median follow-up was 17 months [0.3–60], the median age 60 years, 35 males and 18 females were included. Squamous cell carcinoma (SCC) (60.4%) was the predominant histology, followed by adenocarcinoma (15.1%). The mean composite OS (overall survival) time was 33.3 ± 3.5 months. There was no significant difference in the 5 y composite OS between tumor localization or radiotherapy setting. The simultaneous integrated boost concept showed a trend towards improving five-year composite OS compared to the sequential boost concept. The only factor with a significant impact on the 5 y composite OS rate was the pre-therapeutic GTV (cutoff 75 cm3; p = 0.033). The GTV ≥ 100 cm3 has no effect on the 5 y composite OS rate for SCC. Conclusions: The pre-therapeutic GTV is a prognostic factor for five-year composite OS for the entire group of patients with sinonasal tumors, influencing the outcome after completion of all treatment strategies. The GTV seems to not influence five-year composite OS in SCC. For this rare tumor entity, an intensive, multidisciplinary discussion is essential to finding the best treatment option for the patient.

[LANGUAGE= \"English\"] Objectives: We performed a planning study to evaluate the dosimetric differences between Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) using simultaneous Integrated Boost (SIB) for prostate cancer cases. Methods: 20 prostate cancer patients scheduled for SIB-VMAT treatment on the HalcyonTM 2.0 linear accelerator were recruited for this study and SIB-IMRT plans were generated for comparison purpose. The pelvic lymph nodes (PTV46), the seminal vesicle (PTV50), and the prostate (PTV60) were simultaneously treated to 46 Gy 50 Gy, and 60 Gy delivered in 20 fractions respectively. Results: SIB-VMAT was better due to its higher (1.41%) CI, lower (2.7%) HI, and lower (26%) GI than SIB-IMRT for PTV60. For PTV50, a higher (7.3%) CI, lower (48%) HI, and a lower (31.73%) GI for SIB-VMAT compared to SIB-IMRT. Also, for PTV46, a higher (9.4%) CI, lower (2.5%) HI, and a lower (16.4%) GI were achieved by SIB-VMAT compared to SIB-IMRT. Conclusion: Better conformal and slightly similar homogeneous dose distribution were noticed in SIB-VMAT plans compared to SIB-IMRT plans. However, SIB-IMRT provided better OARs sparing of the bladder and the femoral heads while SIB-VMAT had better sparing for rectum.

Purpose To dosimetrically evaluate different breast SIB techniques with respect to target coverage and organs at risk (OARs) doses. Methods Four IMRT techniques were compared in 12 patients. Three techniques employ tangential whole breast irradiation with either two coplanar fields (T-2F), or four non-coplanar fields (T-NC), or one Volumetric Modulated Arc Therapy (T-VMAT) for the boost volume. The fourth technique is a fully-modulated VMAT technique (f-VMAT). Dosimetric parameters were compared for the boost and breast target volumes as well as OARs. Delivery efficiency was analysed based on number of monitor units (MUs) and estimated delivery time. Results T-VMAT and f-VMAT ranked highest with respect to integral assessment of boost and breast treatment quality measures. T-VMAT significantly outperformed f-VMAT with respect to ipsi-lateral lung and left-sided patients’ heart volumes ≥ 5 Gy (35 % ± 5 % vs. 52 % ± 6 % and 11 % ± 5 % vs. 22 % ± 6 %, respectively). f-VMAT significantly outperformed T-VMAT with respect to ipsi-lateral lung volume ≥ 20 Gy (13 % ± 2 % vs. 15 % ± 3 %) and heart volume ≥ 30 Gy in left breast cancer (0 % ± 0 % vs. 1 % ± 1 %). T-VMAT and f-VMAT needed 442 ± 58 and 1016 ± 152 MUs, respectively. Conclusions The hybrid T-VMAT is considered the technique of choice due to its balance of quality, efficiency and dose to OARs.