Local Failure Rate Research Articles

The Evolving Role of Neoadjuvant Radiation Therapy in Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

A case series and review of stereotactic body radiation therapy for contiguous multilevel spine metastases.

A majority of published series report on stereotactic body radiation therapy (SBRT) for 1-2 contiguous vertebral levels due to concerns regarding setup accuracy and radiation toxicity. This study evaluates patients with metastases spanning ≥ 3 contiguous levels treated with SBRT and augments its findings with a review of other studies investigating multilevel spine SBRT. Analysis of a prospectively collected database of 49 patients with 55 metastases spanning ≥ 3 contiguous vertebral levels treated with SBRT at a single institution (2002-2023) was performed. Outcomes identified included local failure (LF), pain response, overall survival, and toxicity. The median single-fraction prescription dose was 15Gy (range: 8-18); multifractionated treatment utilized prescription doses of 18-30Gy in 2-5 fractions. Median follow-up was 7 months (range: 1-103). The 6-month, 1-year, and 2-year cumulative incidence rates of LF were 7%, 11%, and 11%, respectively. No prognostic factors were associated with LF. Pain was reported to improve or remain stable for 49 lesions (89%). Ten adverse radiation events (18%) were identified; pain flare (5%), dermatitis (4%), and vertebral compression fracture (VCF, 9%). The 3-month, 6-month, and 1-year cumulative incidence rates of VCF were 4%, 7%, and 7%, respectively. No instances of esophageal toxicity or myelopathy were observed. This study of multilevel SBRT is one of the largest to investigate outcomes in this challenging clinical scenario. Spine SBRT confers low rates of LF and toxicity for patients with multilevel disease, which was previously considered a relative contraindication. Spine SBRT may be considered in this patient population instead of low-dose palliative RT.

RADT-02. PRE-OPERATIVE VERSUS POST-OPERATIVE FRACTIONATED STEREOTACTIC RADIOTHERAPY: A SINGLE-INSTITUTION ANALYSIS OF 534 RESECTED METASTASES

Abstract Patients with large or symptomatic brain metastases and limited intracranial disease typically have surgery followed by post-operative (post-op) stereotactic radiosurgery (SRS). However, SRS can lead to elevated rates of radiation necrosis (RN), meningeal disease (MD), and local failure (LF). Fractionated treatments can deliver a higher biological effective dose and may reduce the risk of LF, and pre-operative (pre-op) treatments may reduce the risk of RN and MD through treating smaller volumes and tumor sterilization. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive post-op FSRT. A retrospective analysis was performed at a single institution and included patients who had surgical resection and radiation to at least one brain metastasis. Patients with multiple metastases resected, either during the same surgery or at different times in the disease course, were eligible for inclusion. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. 458 patients with 534 resected brain metastases were eligible for analysis. 235 metastases received pre-op FSRT, and 299 metastases received post-op FSRT. Overall, 15% of patients had multiple brain metastases resected. Overall, 6 (2.6%) pre-op and 13 (4.3%) post-op patients experienced LF. 21 (8.9%) pre-op and 38 (12.7%) post-op patients experienced symptomatic RN. 11 (4.7%) pre-op and 29 (9.7%) post-op patients were diagnosed with MD (p=0.031). 14% and 24% of metastases that received pre-op and post-op FSRT, respectively, experienced the composite endpoint (p=0.005). In our study, pre-op FSRT compares favorably to post-op FSRT primarily due to a 50% reduction in the incidence of MD. Differences in symptomatic RN or LF were small on adjusted analyses. Prospective validation of pre-op FSRT is needed.

RADT-01. PRE-OPERATIVE SINGLE FRACTION VERSUS FRACTIONATED STEREOTACTIC RADIOTHERAPY: A SINGLE-INSTITUTION ANALYSIS OF 299 RESECTED METASTASES

Abstract The treatment standard for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection followed by post-operative (post-op) stereotactic radiosurgery (SRS). The multicenter PROPS-BM cohort showed how pre-operative (pre-op) SRS may lead to a reduced incidence of radiation necrosis (RN), local failure (LF), and meningeal disease (MD) compared to historical controls. Fractionated treatments can deliver a higher biological effective dose and may reduce the incidence of LF and MD. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive pre-op SRS. Patients who had surgical resection and pre-operative radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. 260 patients with 299 resected brain metastases were eligible for analysis. 64 metastases received SRS and 235 metastases received FSRT. 38 patients had multiple metastases resected pre-operatively. The median gross tumor volume was 4 ccs for SRS and 10 ccs for FSRT (p<0.001). Overall, 4 (6.3%) SRS and 6 (2.6%) FSRT patients experienced LF. 4 (6%) SRS and 21 (8.9%) FSRT patients experienced Grade 2 or higher RN. 3 (4.7%) SRS and 11 (4.7%) FSRT patients were diagnosed with MD. 14% of both SRS and FSRT patients experienced the composite endpoint. There were no statistically significant differences in outcome between these two treatment groups. In our study, pre-op SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. It is important to prospectively compare pre-op SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.

Exploratory Evaluation of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR) with CNS-Active Drugs in Brain Metastases Treatment

Brain metastases (BMs) affect an increasing number of cancer patients and are typically managed with stereotactic radiosurgery (SRS). Our institution advocates the use of Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR), where radiation is delivered in high-dose pulses at extended intervals allowing for treatment adaptation and easy concurrent systemic therapy integration. We explore the integration of PULSAR with central nervous system (CNS)- active drugs (CNS-aDs). This study involved a retrospective evaluation of patients treated with PULSAR using Gamma Knife from 2018-2024. We collected demographic, clinical, and specific treatment details, outcomes such as local failure (LF) and toxicity rates. Cumulative incidence analysis for local failure and toxicity, considering death a competing risk, and Kaplan-Meier survival analysis for overall survival (OS) were conducted. Analysis included 109 lesions treated with PULSAR, predominantly in patients with lung and breast cancer. The median follow-up was 1.72. Median OS was not reached. The 1- and 2-year LF rates were 5% and 8.9%, respectively, and 3.4% and 5.5% with concurrent CNS-aDs (cCNS-aDs). BMs > 2 cm had LF rates of 9.4% at two years. No LFs were observed in BMs > 2 cm treated with the combined PULSAR+CNS-aDs approach at 2.5 years. Univariate analysis indicated CNS-aD and radioresponsive histologies were associated with decreased LR rates. The two-year grade 3+ toxicity rate for PULSAR was 8.7%, with no increase in toxicity with cCNS-aDs. The integration of PULSAR with CNS-aDs appears to offer excellent local control for larger brain metastases with limited toxicity. These promising results merit further prospective investigation to validate the findings and potentially establish new treatment protocols.

Supraclavicular lymph node metastasis should not be defined as regional lymph node metastasis in cervical and upper thoracic esophageal squamous cell carcinoma.

The importance of supraclavicular lymph node (SCLN) metastasis in cervical and upper thoracic esophageal squamous cell carcinoma (ESCC) has not been determined. The aim of the present study was to provide a detailed definition of the range of SCLN regions and to explore whether SCLNs should be considered as a regional lymph nodes for patients with cervical and upper thoracic ESCC. A retrospective analysis was performed on 230 patients with locally advanced cervical or upper thoracic ESCC who underwent radical radiotherapy and chemotherapy. The range of SCLN regions was defined in detail on contrast enhanced computed tomography images of the neck. According to whether the patient had lymph node metastasis in the supraclavicular region, the included patients were divided into two groups, and the survival differences and reasons for treatment failure between the two groups were analyzed. Of the 230 patients with ESCC, 71 (30.87%) exhibited lymph node metastases in the supraclavicular region. The median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 30 months, respectively (P<0.001). After propensity score matching (PSM), the median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 28 months, respectively (P<0.001). During the follow-up period, there were a total of 101 cases of failure of treatment in the irradiation field, 6 cases had esophageal metastasis in the non-irradiated field and 27 cases had regional lymph node metastasis in the non-irradiated field. In addition, there were 33 cases of metastasis to the distant lymph nodes or organs. There was no significant difference in the local treatment failure rate between the groups with or without SCLN metastasis in both the irradiation field and the non-irradiation field, but the probability of distant metastasis in the SCLN metastasis group was significantly higher than that in the group without SCLN metastasis (P=0.025). In conclusion, patients with cervical and upper thoracic ESCC with SCLN metastasis have a poor prognosis and the median overall survival time is closer to that of metastatic ESCC than ESCC with regional lymph node metastasis; therefore, SCLNs should not be defined as regional lymph nodes in patients with cervical and upper thoracic ESCC.

Outcomes for patients with perineal and perianal rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee.

To describe clinical features, risk factors, and outcomes of patients with perineal and perianal rhabdomyosarcoma. The records of 51 patients (38 perineal and 13 perianal) enrolled on Children's Oncology Group clinical trials between 1997 and 2012 were reviewed. At presentation, 53% were female, 65% were older than 10years of age, 76% were alveolar histology, 76% were more than 5cm, 84% were invasive, 65% were regional node positive by imaging, 49% were metastatic, only 16% were grossly resected upfront, and 25% of patients had a delayed excision. At a median follow-up of 6.13years, estimated 5-year event-free survival (EFS) was 38% [22.17%-53.38%], and overall survival (OS) was 42% [26.66%-58.21%]. The rates of local, regional, and distant failure were 15.6%, 13.7%, 43.1%, respectively; all failures ultimately died. By univariate analysis, only age more than 10years negatively impacted 5-year EFS (p=.023) and OS (p=.09), and IRS Group also impacted OS (p=.043). In Cox proportional hazards model, neither of these variables were significant after adjusting for other factors. Patients with perineal and perianal rhabdomyosarcoma have a poor overall prognosis, probably related to poor patient and disease characteristics at presentation.

Effect of Treatment Delivery Schedule for Patients With Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy: A Population-Based Analysis

PurposeThe optimal stereotactic ablative body radiotherapy (SABR) delivery schedule in stage I non-small cell lung cancer (NSCLC) remains unclear. This population-based study investigated grade ≥ 2 toxicity rates, local failure (LF), and overall survival (OS) in patients treated with 48 Gy in 4 fractions scheduled every other day (QOD) versus daily with weekends (QDW) and consecutive daily without weekends (QD). Materials and MethodsBetween January 2019 and June 2022, treatment records using 48 Gy in 4 fractions were extracted from a provincial cancer registry and grouped by delivery as QOD, QDW, or QD. Toxicity events were recorded using CTCAE v5.0. The Kaplan-Meier method was used to compute OS while LF was calculated using cumulative incidence methods with death as a competing risk. Cox regression analyses and Fine-Gray modelling was used to assess for variables associated with OS and LF, respectively. ResultsOf 404 patients meeting study criteria, 190, 111, and 103 received QOD, QDW, and QD SABR, respectively. More patients receiving QDW SABR were medically inoperable and more patients receiving QD SABR had tumors abutting the chest wall. Median follow-up was 29.5 months (interquartile range [IQR] 19.2-38.4). Overall toxicity was low, with crude rates of acute and late grade ≥ 2 toxicity not being statistically different among the groups. No grade 4 or 5 toxicities were recorded. LF rates at 24 months were not different at 7.5% (95% confidence interval [CI] 3.7-11.3), 9.5% (95% CI 3.9-15.1), and 11.0% (95% CI 4.9-17.2) for the QOD, QDW, and QD groups, respectively (p = 0.60). QDW and QD schedules were not associated with LR. Similarly, no significant differences in median OS were found among the QOD, QDW, and QD groups at 47.5 months (95% CI 39.26-55,74), 52.7 (95% CI 34.7-70.7), and 49.0 months (95% CI 31.6-66.4), respectively. QDW and QD schedules were not associated with OS. ConclusionsThis population-based study demonstrated no statistically significant differences in grade ≥ 2 toxicity rates, LF, and OS for stage I NSCLC patients treated with lung SABR using 48 Gy in 4 fractions delivered QOD, QDW, and QD. Patient convenience and optimization of resources may be considered when choosing a lung SABR treatment delivery schedule.

Multifraction stereotactic radiotherapy utilizing inhomogeneous dose distribution for brainstem metastases: a single-center retrospective analysis.

Brainstem metastases are challenging to manage owing to the critical neurological structures involved. Although stereotactic radiotherapy (SRT) offers targeted high doses while minimizing damage to adjacent normal tissues, the optimal dose fractionation remains undefined. This study evaluated the efficacy and safety of multifraction SRT with an inhomogeneous dose distribution. This retrospective study included 31 patients who underwent 33 treatments for 35 brainstem lesions using linear accelerator-based multifraction SRT (30Gy in five fractions, 35Gy in five fractions or 42Gy in 10 fractions) with an inhomogeneous dose distribution (median isodose, 51.9%). The outcomes of interest were local failure, toxicity and symptomatic failure. The median follow-up time after brainstem SRT for a lesion was 18.6months (interquartile range, 10.0-24.3months; range, 1.8-39.0months). Grade 2 toxicities were observed in two lesions, and local failure occurred in three lesions. No grade 3 or higher toxicities were observed. The 1-year local and symptomatic failure rates were 8.8 and 16.7%, respectively. Toxicity was observed in two of seven treatments with a gross tumor volume (GTV) greater than 1cc, whereas no toxicity was observed in treatments with a GTV less than 1cc. No clear association was observed between the biologically effective dose of the maximum brainstem dose and the occurrence of toxicity. Our findings indicate that multifraction SRT with an inhomogeneous dose distribution offers a favorable balance between local control and toxicity in brainstem metastases. Larger multicenter studies are needed to validate these results and determine the optimal dose fractionation.

Clinical Outcomes of 3 Versus 4 Fractions of Magnetic Resonance Image-Guided Brachytherapy in Cervical Cancer

PURPOSEMRI-guided brachytherapy (MRgBT) is essential in the management of locally advanced cervical cancer. This study compares disease and toxicity outcomes in cervical cancer patients treated with 24 Gy/3 fractions (Fr) versus the conventional 28 Gy/4 Fr. METHODS AND MATERIALSThis retrospective study included 241 consecutive patients with FIGO 2018 stage IB-IVA cervical cancer treated with definitive chemoradiation between April 2014 - March 2021. Disease-free survival (DFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Cumulative incidence of local failure (LF), distant failure (DF) and G2+ gastrointestinal (GI), urinary (GU) and vaginal toxicity were estimated using the cumulative incidence function with death as a competing risk and compared using the Gray's test. RESULTSOf the 241 patients, 42% received 24 Gy/3 Fr and 58% received 28 Gy/4 Fr. With a median follow up of 3.2 (range 0.2-9.2) years, there were 14 local, 41 regional nodal and 51 distant failures in 63 (26%) patients. No significant differences were found between the 24 Gy/3 Fr vs 28 Gy/4 Fr group in 3-year DFS (77% vs 68%, P = 0.21), 3-year cumulative incidence of LF (5% vs 7%, P = 0.57), DF (22% vs 25%, P = 0.86), G2+ GI toxicity (11% vs 20%, P = 0.13), or G2+ vaginal toxicity (14% vs 17%, P = 0.48), respectively. The 3-year cumulative G2+ urinary toxicity rate was lower in the 24 Gy/3 Fr group (9% vs 23%, P = 0.03). CONCLUSIONCervical cancer patients treated with 24 Gy/3 Fr had similar DFS, LF, DF, GI and vaginal toxicity rates, and a trend towards lower G2+ urinary toxicity rate compared to those treated with 28 Gy/4 Fr. A less resource-intensive brachytherapy fractionation schedule of 24 Gy/3 Fr is a safe alternative to 28 Gy/4 Fr for definitive treatment of cervical cancer.

Comparative evaluation of outcomes amongst different radiosurgery management paradigms for patients with large brain metastasis.

This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS). Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray's test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data. 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology. This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches.

Radiation dose escalation and local control for intermediate-risk rhabdomyosarcoma on ARST1431: A report from the Children’s Oncology Group

10007 Background: The objective of this study was to evaluate local failure (LF) rates for patients with intermediate-risk rhabdomyosarcoma (IR-RMS) treated on the Children’s Oncology Group (COG) ARST1431 clinical trial. To improve local control, the radiation therapy (RT) dose was increased to 59.4 Gy for patients with tumors &gt; 5cm at diagnosis and residual gross disease at the time of RT. Methods: The297 patients randomized on ARST1431 were included. LF was defined as progression or relapse at the primary tumor site. Gray’s test was used to compare the cumulative incidence of LF across variables. Results: There was a trend for lower 3-year LF in group III patients with fusion-positive disease (11.1%, 95% confidence interval (CI) 4.5%-21.1%) compared to patients with fusion-negative disease (21.8%, 95% CI 15.8%-28.4%), p = 0.09.There was no difference in the 3-year LF rate for patients who underwent proton RT (16.3%, 95% CI 9.6%-24.7%) compared to photon RT (16.2%, 95% CI 10.2%-23.6%;), p = 0.8. The 3-year LF rate for all patients with tumors &gt; 5cm at diagnosis (24.9%, 95% CI 18.6%-31.7%) was significantly higher than that of patients with tumors ≤5cm at diagnosis (9.9%, 95% CI 5.2%-16.4%), p &lt; 0.01. Of 81 patients with tumors &gt; 5cm and residual gross disease after induction chemotherapy who went on to receive RT, 62 (76.5%) received the protocol-specified boost to 59.4 Gy. Patients who received the boost had a 3-year LF rate of 32.1% (95% CI 20.1%-44%), while patients who did not undergo an RT boost had a 3-year LF rate of 16.1% (95% CI 3.8%-36.2%), p = 0.3. For patients with group III, non-parameningeal disease, those who underwent delayed primary excision (DPE) had a significantly lower LF rate compared to those who did not undergo DPE (3-year rate of 5.6% (95% CI 1.4%-14.0%) vs. 22.0% (95% CI 14.5-30.7%), p &lt; 0.01). Conclusions: On ARST1431, larger tumors ( &gt; 5cm at diagnosis) were associated with increased risk of LF. Dose escalation to 59.4 Gy did not improve local control for patients with tumors &gt; 5cm at diagnosis with residual gross disease at the time of RT. For a select group of non-parameningeal, group III patients who underwent DPE followed by RT, local control was improved. Clinical trial information: NCT02567435 .

Stereotactic radiosurgery for prostate cancer spine metastases: local control and fracture risk using a simultaneous integrated boost approach.

Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases. Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence. A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear. High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.

Disease Control and Toxicity Outcomes after Stereotactic Ablative Radiation Therapy for Recurrent and/or Metastatic Cancers in Young-Adult and Pediatric Patients.

Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan-Meier estimates in R v4.2.3. In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14-23 y) and the median follow-up was 18.1 months (IQR: 7.7-29.1). The median SABR dose was 30 Gy (IQR 25-35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

Systematic evaluation and meta-analysis of the prognosis of down-staging human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma using cetuximab combined with radiotherapy instead of cisplatin combined with radiotherapy.

To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Meta-analysis and systematic evaluation. The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], P = 0.0004; HR = 1.79, 95% CI [1.40-2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], P < 0.0001; HR = 1.66, 95% CI [1.07-2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], P = 0.28). Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. CRD42023445619.

Patient-reported outcomes after personalised dose-escalation for stage II-III non-small-cell lung cancer patients: Results from the randomised ARTFORCE PET-Boost trial

Background and purposeThe ultimate challenge in dose-escalation trials lies in finding the balance between benefit and toxicity. We examined patient-reported outcomes (PROs), including health-related quality of life (HRQoL) in patients with locally advanced non-small cell lung cancer (LA-NSCLC), treated with dose-escalated radiotherapy. Materials and methodsThe international, randomised, phase 2 ARTFORCE PET-Boost study (NCT01024829) aimed to improve 1-year freedom from local failure rates in patients with stage II-III NSCLC, with a ≥ 4 cm primary tumour. Treatment consisted of an individualised, escalated fraction dose, either to the primary tumour as a whole or to its most FDG-avid subvolume (24 x 3.0–5.4 Gy). Patients received sequential or concurrent chemoradiotherapy, or radiotherapy only. Patients were asked to complete the EORTC QLQ-C30, QLQ-LC13, and the EuroQol-5D at eight timepoints. We assessed the effect of dose-escalation on C30 sum score through mixed-modelling and evaluated clinically meaningful changes for all outcomes. ResultsBetween Apr-2010 and Sep-2017, 107 patients were randomised; 102 were included in the current analysis. Compliance rates: baseline 86.3%, 3-months 85.3%, 12-months 80.3%; lowest during radiation treatment 35.0%. A linear mixed-effect (LME) model revealed no significant change in overall HRQoL over time, and no significant difference between the two treatment groups. Physical functioning showed a gradual decline in both groups during treatment and at 18-months follow-up, while clinically meaningful worsening of dyspnoea was seen mainly at 3- and 6-months. ConclusionIn patients with LA-NSCLC treated with two dose-escalation strategies, the average patient-reported HRQoL remained stable in both groups, despite frequent patient-reported symptoms, including dyspnoea, dysphagia, and fatigue.

ESHO 1–85. Hyperthermia as an adjuvant to radiation therapy in the treatment of locally advanced breast carcinoma. A randomized multicenter study by the European Society for Hyperthermic Oncology

BackgroundThe ESHO protocol 1–85 is a multicenter randomized trial initiated by the European Society for Hyperthermic Oncology with the aim to investigate the value of hyperthermia (HT) as an adjuvant to radiotherapy (RT) in treatment of locally advanced breast carcinoma. The trial is one of the largest studies of hyperthermia in radiotherapy but has not been previously published. Patients and methodsBetween February 1987 and November 1993, 155 tumors in 151 patients were included. Tumors were stratified according to institution and size (T2-3/T4) and randomly assigned to receive radiotherapy alone (2 Gy/fx, 5 fx/wk) to a total dose of 65–70 Gy, incl. boost, or the same radiotherapy followed once weekly by hyperthermia (aimed for 43 °C for 60 min). Radiation was given with high voltage photons or electrons. The primary endpoint was persistent complete response (local control) in the treated area. ResultsA total of 146 tumors in 142 patients were evaluable, with a median observation time of 19 (range 1–134) months. Seventy tumors were randomized to RT alone and 76 to RT + HT. Size was T4 in 92, and T2-3 in 54 tumors, respectively. The compliance to RT was good with all but 4 patients fulfilling the planned RT treatment. The tolerance to HT was fair, but associated with moderate to severe pain and discomfort in 15 % of the treatments. In 84 % of the heated patients a least one heat treatment achieved the target temperature, but the temperature variation was large. Addition of heat did not significantly increase the acute nor late radiation reactions.Overall, the 5-year actuarial local failure rate was 57 %. Univariate analysis showed a significant influence of hyperthermia (RT alone 68 % versus RT + HT 50 %, p = 0.04, and T-size (T4 75 % versus T2-3 36 %, p < 0.01). A Cox multivariate analysis showed the same factors to be the only significant prognostic parameters: hyperthermia (HR: 0.61 [0.38–0.98], and small tumor strata (HR: 0.46 [0.26–0.92]. Consequentially, more patients given RT + HT (36 %) survived without disease (DFS), than after RT alone (19 %), p = 0.021) ConclusionA randomized multicenter trial investigating the addition of a weekly hyperthermia treatment to radiotherapy of patients with locally advanced breast cancer significantly enhanced the 5-year tumor control and yielded more patients surviving free from cancer. The results substantiate the potential clinical benefit of hyperthermic oncology.

Ultra‐low dose radiation therapy for primary cutaneous indolent B‐cell lymphomas

AbstractBackgroundPrimary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma (PCMZL) are indolent radiosensitive lymphomas, with national guidelines recommending 24 Grey (Gy) in 12 fractions, despite shorter regimens showing no difference in overall survival. Multiple studies demonstrate 4 Gy in two fractions is effective in other indolent lymphomas. Shorter regimens may result in less toxicity for patients.ObjectivesWe aim to characterise local control rates in PCFCL and PCMZL treated with radiation therapy (RT) with 4 Gy in two fractions.MethodsFrom a single institution database, we retrospectively identified all patients with PCFCL and PCMZL treated with 4 Gy in two fractions between 2011 and 2022. Prior topical or systemic treatments were permitted. T‐cell or high‐grade B‐cell cutaneous lymphomas, or those with less than 6 months follow‐up, were excluded. Primary outcomes were rates of response and local failure per lesion as determined by a radiation oncologist and oncologic dermatologist.ResultsForty‐three consecutive patients with 98 lesions treated were identified. Twenty‐four (56%) of the patients had PCMZL, and the remainder had PCFCL. Most lesions (97%) received RT with electrons. The complete response or partial response rate was 94%. Six local failures were identified (6%). With a median follow‐up of 2.75 years, 1‐, 2‐ and 3‐year local failure‐free survival were 94%, 94% and 92%, respectively. There was minimal acute toxicity, no late toxicity and no cosmesis issues. No clinical features were predictive of local failure.ConclusionsUltra‐low dose radiation was associated with high rates of local control and minimal toxicity and may reduce personal burden and financial toxicity in appropriately selected patients.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review

Purpose/Objective(s)We sought to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for ultra-central thoracic tumours at our institution. Materials/MethodsPatients with ultra-central lung tumours or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS) and overall survival (OS). Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. Results154 patients receiving 162 ultra-central courses of SBRT were included. The most common prescription was 50Gy in 5 fractions (42%), with doses ranging from 30-55Gy in 5 fractions (BED10 range 48-115Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n=4). There was 1 possible treatment related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5Gy, and lung V20Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age, and greater volume of overlap between the PTV and esophagus. Median PFS was 8.8 months, while median OS was 44.0 months. ConclusionIn the largest case series of ultra-central thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed.

Experimental study on the progressive collapse mechanism of excavations retained by tied-back retaining systems

Progressive collapses of tied-back excavations caused by the failure of some anchors often occur. However, the mechanism through which partial failure evolves to global failure and how the local failure rate influences progressive collapse has not been investigated. In this study, anchor failure experiments involving tied-back excavation were designed to explore the load transfer path and rule in the case of partial anchor failure. The results showed that, anchor failure leads to an increase in the axial force on adjacent anchors, an increase in the maximum bending moment of capping beams, and easy damage in capping beams due to structural reinforcement. The lower the anchor elevation is, the greater the excavation depth, and the greater the load transfer coefficient (axial force). The failure rate of anchors has an effect on the stress redistribution of the structure and the soil arching effect. In multi-row anchored pile retaining excavations, more rows of anchor failure could trigger the remaining anchors failure because the load transfer coefficient (axial force) is greater for these anchors, which leads to large-scale excavation collapse.