Upfront Radiotherapy Research Articles

Patterns of Care in Craniopharyngioma: Clinical Outcomes After Surgery and Radiation Therapy in a Real-World Setting

Craniopharyngioma (CP) is a benign neuroepithelial tumor generally treated with maximal safe resection and radiation therapy (RT) in incompletely resected CP or in recurrent tumors to achieve long-term control. We analyzed the clinical outcomes of patients with CPs treated with a multimodality approach. A retrospective clinical audit of histologically proven CPs registered between 2008 and 2019 at a specialized neuro-oncology center in India was performed. Time-to-event outcomes (overall survival [OS] and progression-free survival [PFS]) were analyzed. One hundred and twenty-two patients with CP were analyzed. The median age of the population was 14 years (interquartile range [IQR], 8-26) with a significant male preponderance. Gross total resection was achieved in only 25% of patients. At a median follow-up of 57.1 months (IQR, 27.8-87.8), 5-year estimates of PFS and OS were 52% (95% confidence interval, 46%-63.4%) and 85.8% (95% confidence interval, 78.6%-93%), respectively. Recurrence or progression was observed in 48 of 122 patients (39.3%) at a median time of 84.4 months (IQR, 24.7-174.8). On multivariate analysis, the absence of residual disease (P= 0.004), near-total resection (P= 0.035), and use of up-front adjuvant RT (P < 0.001) significantly improved the 5-year PFS, whereas the absence of extracavernous extension (P= 0.058) and any use of postoperative RT (P= 0.026) significantly improved the 5-year OS. This study represents one of the largest single-institutional series of CPs, showing improved PFS with up-front adjuvant RT in most cases of CP. Deferring adjuvant RT should be considered only in patients with no evidence of residual disease (as shown on dedicated sellar imaging) after primary surgery.

First-line treatment with TKI plus brain radiotherapy versus TKI alone in EGFR-mutated non-small cell Lung cancer with brain metastases: a systematic review and meta-analysis

BackgroundIt remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is superior to EGFR-TKIs alone for EGFR-mutated non-small cell lung cancer with newly diagnosed brain metastases (BMs). Therefore, we performed a meta-analysis to address this issue.MethodsWe searched PubMed, Embase, Cochrane Library, and Web of Science databases for eligible studies published until February 28, 2023. The primary outcomes of interest were overall survival (OS) and intracranial progression-free survival (iPFS), reported as hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsTwenty-four retrospective studies with 3184 patients were included. First- or second-generation EGFR-TKIs were used in each study. Upfront brain RT plus EGFR-TKIs significantly prolonged OS (HR = 0.75, 95% CI: 0.64–0.88) and iPFS (HR = 0.61, 95% CI: 0.52–0.72) compared to EGFR-TKIs alone. There were no significant differences in OS and iPFS benefits from the combination therapy between asymptomatic and symptomatic patients, patients with exon 19 and 21 mutations, patients with 1–3 and > 3 BMs, and males and females, respectively (HRs interaction, P > 0.05 for each subgroup comparison).ConclusionsFirst-line treatment with upfront brain RT plus EGFR-TKIs is likely to be more effective than EGFR-TKIs alone. The benefits of combination therapy did not appear to be significantly affected by BM-related symptoms, EGFR mutation subtype, number of BMs, or sex.

Improved survival outcome with not-delayed radiotherapy and immediate PD-1/PD-L1 inhibitor for non-small-cell lung cancer patients with brain metastases

PurposeTo investigate the impact of radiotherapy (RT) and immune checkpoint inhibitor (ICI) sequence on the survival outcome in NSCLC patients with brain metastasis, and decide the best time to initiate RT.MethodsPatients were managed with delayed RT (ICI delivered over 2 weeks prior to RT), concurrent RT (ICI delivered within 2 weeks prior to or after RT), or upfront RT (RT delivered over 2 weeks prior to ICI). Overall survival (OS), intracranial local progression-free survival (iLPFS), and intracranial distant progression-free survival (iDPFS) were assessed. A meta-analysis was performed to analyze the association between survival outcome and RT/ICI sequence.ResultsA total of 73 NSCLC patients were identified with a median follow-up of 13.9 months. Patients who receive delayed RT demonstrated shorter iLPFS (P = 0.0029), iDPFS (P = 0.016), and OS (P < 0.001). A meta-analysis was conducted and a total of 4 studies, 254 patients were included. The HR was 0.44 for iDPFS (P = 0.03), 0.41 for OS (P < 0.01) when compared concurrent with delayed RT, 0.21 for iDPFS (P < 0.01), 0.32 for OS (P < 0.01) when compared upfront with delayed RT, consistent with our conclusion that delayed RT brought with worst iDPFS and OS. More importantly, the best overall response rate (BOR) decreased in cases with longer RT and ICI intervals. Patients who receive intervals of RT and ICI within 7 days achieve the best median BOR of − 53%.ConclusionsDelayed RT brought poor survival outcomes including iLPFS, iDPFS, and OS in NSCLC patients. The shorter interval of RT and ICI is associated with better BOR.

The Role of Radiation Therapy in the Management of Gray Zone Lymphoma.

Gray zone lymphoma (GZL) is a relatively rare disease predominantly affecting young adults with purportedly poor outcomes with current treatment approaches. The role of radiation therapy (RT) in the management of GZL is not well established. This is the largest study to report on the outcomes of GZL patients treated with and without RT. A retrospective review of 30 patients with GZL treated across 3 institutions from 2009 to 2021 was performed. Event-free survival (EFS) was defined from initiation of frontline chemotherapy (CHT) to disease progression/relapse, initiation of salvage therapy, or death. Local control (LC) was defined from RT start date to in-field recurrence. The median age was 32 (range: 18-86) years, and 16 (53%) patients had early stage (I-II) disease. Bulky mediastinal disease was present in 63% of patients, and the median tumor diameter was 10 (range: 1.5-18) cm. Patients received ABVD (20%), RCHOP (33%), or REPOCH (47%) as frontline CHT. Among 25 patients with interim PET/CT scan, there were 6 rapid early responders and 14 slow early responders (SER), with 2-year EFS of 33% and 24%, respectively (p = 0.13). After the completion of CHT, 15 (50%) patients achieved complete response (CR) and 10 (33%) achieved partial response (PR), with 2-year EFS of 46% and 10%, respectively (p = 0.004). RT was given to 9 patients in CR (n = 3) or in PR (n = 6). The median RT dose was 36 (30.6-48.6) Gy, at 1.8-2 Gy/fraction. Those receiving RT had bulkier disease at diagnosis (p = 0.049) and lower rates of CR following CHT (p = 0.03). After RT, 3/6 (50%) PR patients converted to CR. At a median follow-up of 4 years, the 2-year EFS was 26% for all patients, 33% for RT and 23% for noRT (p = 0.44). Among patients who did not receive upfront RT and experienced progression (n = 17), 16 (94%) relapsed in pre-existing sites. The 5-year OS was 80% for all patients, 88% for RT and 78% for no RT (p = 0.63). Patients who achieved PR to CHT and received RT had better 2-year EFS (17% vs 0%, p = 0.007) compared to patients who did not receive RT. Similarly, patients with SER who received RT had superior 2-year EFS (33% vs 13%, p = 0.038). Patients with bulky mediastinal disease had a 2-year EFS of 43% with RT and 11% without RT (p = 0.08). After 1st line treatment, 22 (73%) patients relapsed and 18 were successfully salvaged with a sustained CR. The most common salvage regimen involved high dose CHT followed by hematopoietic cell transplantation (HCT) (n = 15). RT was given for 7 patients in the relapsed/refractory setting (consolidative peri-HCT n = 4; definitive salvage n = 3) and 5 (71%) achieved a sustained CR. Among the 16 patients who received RT in the upfront (n = 9) or salvage (n = 7) setting, 3 patients experienced in-field recurrence translating to 2-year LC of 79%. GZL patients have high risk of relapse and maximal upfront combined modality therapy should be considered. RT provides good local control and improves EFS particularly for SER, PR, and bulky mediastinal disease.

Outcomes Following Radiation Therapy (RT) for Very Young Age CNS Embryonal Tumors on COG ACNS0334 According to Molecular-Confirmed Diagnosis

The outcomes of upfront or relapse radiation therapy (RT) for the Children's Oncology Group ACNS0334 protocol based on molecular diagnosis were assessed. Therapy included maximal safe surgery, high-dose chemotherapy with stem cell rescue, randomization for inclusion of high dose methotrexate (MTX) and optional RT. There were 24 patients that received RT on COG ACNS0334 of 77 evaluable patients with a diagnosis of either high-risk medulloblastoma (MB) or supratentorial primitive neuroectodermal tumor (SPNET). RT was a recommendation (M0: Focal, M+: CSI 18 Gy) given young patient age <36 months at enrollment. Seven RT patients were excluded for ineligible pathology (1 ATRT, 1 HGG) or insufficient tissue. The aim of this report is to review outcomes of 17 patients on ACNS0334 receiving RT (8 Upfront, 9 at relapse) with a molecular diagnosis that included MB, Pineoblastoma (PB), or Embryonal tumor with multilayered rosettes (ETMR). In the MB group, there were 9 patients irradiated with MB (Group 3 = 8, SHH = 1). 5-year OS for MB Group 3 receiving RT (median primary dose 54 Gy) was 62.5% with no difference observed comparing 6 patients treated with upfront RT versus 2 treated at relapse (p = 0.27). All upfront RT for MB Group 3 had initial partial response (PR) to 0334 chemotherapy. RT delivery for upfront RT MB Group 3 included craniospinal radiation (CSI) in 5 patients and 1 patient who received focal RT to the primary (50 Gy) and metastatic site (44 Gy). Eighty percent of CSI for upfront RT in Group 3 was 18 Gy or 23.4 Gy. Relapse RT for MB Group 3 (2 patients) utilized full dose CSI (36 Gy, 39.6 Gy) and both patients are survivors with 5+ years follow-up. CSI dose for Group 3 MB was higher for relapse RT (mean 37.8 Gy) as compared to upfront RT (mean 19.8 Gy, p = 0.013). Use of MTX was 50% in both upfront RT and relapse RT Group 3 MB cohorts. One patient with MB SHH (classic histology) underwent upfront focal RT (54 Gy) after initial PR to systemic therapy (without MTX) and is surviving 5+ years. PB: Of 4 PB patients (median primary dose 48.8 Gy) 1 had RT upfront (CSI 18 Gy) and 3 had RT at relapse (1 patient received CSI, 21 Gy). All patients with PB expired within 2 years. MTX was given in 75% (including 1 upfront RT PB). Two of 3 patients treated at relapse had prior complete response (CR). ETMR: All 4 patients (median primary dose 54 Gy) with ETMR were treated at relapse, with CSI given in 1 patient (23.4 Gy). All patients with ETMR expired within 2 years, and 2 (50%) had received MTX. Two patients (50%) had initial CR. The RT cohort for Group 3 MB on ACNS0334 exhibited long-term survival both for both upfront and relapse RT, however relapsed Group 3 MB received higher dose CSI. RT upfront for MB, including one surviving MB SHH patient receiving focal RT, was solely given for incomplete initial chemotherapy response. There were no survivors for either PB or ETMR when the majority (88%) were treated at relapse.

Proliferation Saturation Index to Simulate Adaptive Radiation Fractionation in HPV-Associated Oropharyngeal Cancer

In current clinical practice for fractionated radiotherapy (RT) patients receive a fixed fractionation protocol throughout radiation course. Radiation oncology has not yet moved toward adaptive fractionation to change RT fractionation based on individual patients' response dynamics. We have previously introduced a novel mathematical and imaging biomarker, proliferation saturation index (PSI), to simulate and evaluate tumor volume dynamics during therapy. Robust tumor volume reduction was associated with lower PSI, and PSI has been utilized to select fractionation schedules for the first mathematical model informed clinical trial. Here we simulate the possibility of adapting the selection of RT fractionation on a week-by-week basis by utilizing a dynamic weekly estimation of PSI. We generated a cohort of in silico patients by sampling from distributions of PSI, radiosensitivity, and growth rate parameters. These distributions were by pre-treatment and on-treatment tumor volume dynamics from a prospective clinical trial (NCT03656133), where 49 HPV+ OPC patients were treated with either 2 Gy daily fractions up to a total of 70 Gy if PS<0.75, or hyperfractionation at 1.2 Gy b.i.d. up to a total of 66 Gy for patients with PSI ≥ 0.75. We then simulated standard (2 Gy q.d.) and hyperfractionated (1.2 Gy b.i.d) for 1-8 weeks of RT to build a library of response dynamics for the different parameter combinations and treatment durations. This library was then used to estimate optimal adaptive fractionation schedules for the in silico patients that maximized tumor volume reduction and minimized total RT dose. We found that PSI evolved towards lower values (i.e., higher proliferative fractions) over the fractionation RT treatment course. For patients that began treatment with standard fractionation, no adaption was found to be superior to uniform fractionation. For selected patients who began treatment with hyperfractionation, however, the optimal fractionation schedule included a period of upfront hyperfractionated RT followed by a switch to standard fractionation at different times during their treatment course. The results of this study suggest that in addition to selecting the best initial fractionation schedule, a novel approach to personalize RT for OPC patients may include adapting the fractionation based on early treatment response dynamics. These results motivate validation in prospective clinical trials.

Adjuvant Radiotherapy in Atypical Meningioma: Are the Risks Worth the Benefit?

Adjuvant radiotherapy (RT) improves progression-free survival (PFS) in atypical meningiomas. Herein, we assess whether the treatment-related acute and long-term toxicity of upfront RT in atypical meningioma patients versus surveillance merits the PFS benefit. In our prior single institution retrospective study of 230 patients with resected intracranial atypical meningiomas between 2000-2015, adjuvant RT was associated with a significantly lower risk of progression/recurrence compared to surveillance (HR = 0.21 [95% CI 0.11-0.41]; p<0.01), with 36% of surveillance patients eventually requiring salvage RT. In the current study, the acute (≤6 months) and long term (>6 months) RT-related toxicities from the same patient cohort for those who received adjuvant RT (n = 51) were evaluated and compared to those who received salvage RT (n = 64) in the surveillance group. Additionally, overall treatment-related toxicity at time of last follow up was obtained for comparison between the adjuvant RT (n = 51) vs surveillance (n = 179) group. All toxicities were graded per CTCAE v5.0. Kaplan-Meier analysis was used to calculate the cumulative incidence of toxicities; Pearson's chi-squared and log-rank test were used for comparison. Adjuvant RT as compared to salvage RT was generally associated with greater RT-related toxicities both in the acute (90% vs 69%, p = 0.006) and long term (57% vs 33%, p = 0.010). While there was no significant difference in grade 3-4 acute toxicities, long term grade 3-4 toxicities (including headache, seizure, vision loss, neuromotor deficit, and neurocognitive deficit) were present in 14% of adjuvant vs 3% of salvage RT group (p = 0.035). Radionecrosis occurred in 18% of adjuvant RT vs 8% of salvage RT group (p = 0.11). Between adjuvant RT vs surveillance groups, any-treatment related toxicity at last follow up was greater with adjuvant RT (31% vs 15%; p = 0.006), with trend towards greater grade 3-4 toxicities (including headache, vision loss, neuromotor deficit, neurocognitive deficit, and cerebral edema) as well (8% vs 3%; p = 0.101). Cumulative incidence of treatment-related neuromotor deficit (any grade) was significantly greater in the adjuvant RT vs surveillance group with 14% vs 2% at 10 years (p = 0.004). There was no difference in rate of cerebrovascular accident between adjuvant RT (6%) vs surveillance (4%) groups (p = 0.83). Adjuvant RT for patients with atypical meningioma was associated with greater acute and long-term treatment toxicities. Potential RT-related toxicity and impact on quality-of-life should thus be carefully weighed against the tumor control benefit of RT in deciding the optimal use and timing of RT.

Dosimetric Impact of Systematic Mediastinal Staging via Endobronchial Ultrasound for Patients with Locally Advanced Lung Cancer: The SEISMIC Trial

The SEISMIC trial aims to find the best method for mediastinal staging in patients with lung cancer receiving chemoradiotherapy. Currently, CT or PET-CT scans are standard in clinical practice, but histological evaluation of the mediastinum is performed on a case-by-case basis. The study will examine the effect of systematic histological evaluation using Endobronchial Ultrasound (EBUS) on radiotherapy target volumes. The hypothesis of this study is that differences in staging between the diagnostic PET-CT and EBUS would result in reduced tumor coverage and/or increased doses to organs at risk (OAR). SEISMIC is a prospective multicenter international cohort study. Patients were enrolled from Australia, the Netherlands, USA and Canada after regional IRB approvals. Patients were treated with 4DCT simulation. Two iGTV and PTV target volumes were delineated for each patient with discordant staging according to both PET-CT and EBUS, as were OARs. Two VMAT plans were generated for each patient based on either PET-CT or EBUS target volumes using knowledge-based planning methodology. Plans aimed to achieve institutional guidelines for target coverage and OAR dose constraints, with a prescribed dose of 60 Gy in 30 fractions. Target coverage and OAR doses for the PET- and EBUS-defined volumes were compared. In 156 patients, EBUS showed a larger extent of disease than PET in 18 (11.5%) and a smaller extent of lymph node (LN) involvement than PET in 49 (31.4%). Out of 67 patients with PET-EBUS discordant results, 25 underwent upfront radiotherapy and were included in the study. EBUS revealed PET-occult LN involvement in 11/25 patients (44%). In these patients, 10/11 patients received <95% of the prescribed dose to PET-occult LN iGTVs; the median [range] minimum dose to the EBUS iGTV was 9.2 Gy [0.1 - 57.9 Gy]. When planning based on EBUS LN involvement, all patients received ≥95% of the prescribed dose to the iGTV (the median [range] minimum dose to the EBUS iGTV was 58.9 Gy [58.1 - 60.5 Gy]). This resulted in increased median [range] doses to OARs; mean lung dose increased by 1.1 Gy [0.3 - 8.4 Gy], esophagus mean dose increased by 3.6 Gy [0.2 - 24.8 Gy], and mean heart dose increased by 0.5 Gy [-0.6 - 8.5 Gy]. Systematic endoscopic evaluation of the mediastinum had a significant effect on tumor coverage in a clinically meaningful proportion of cases and consequent plan adaptation impacted on organ-at-risk (OAR) doses. Results suggest systematic mediastinal LN staging should be considered in all patients prior to curative-intent radiotherapy. ACTRN12617000333314.

Upfront Osimertinib Alone vs. Osimertinib and Radiotherapy for the Treatment of EGFR-Positive NSCLC Brain Metastases: A Multi-Institutional Series

Given the increased brain penetrance of osimertinib, the role of upfront radiotherapy (RT) has been questioned for the management of patients with EGFR+ NSCLC brain metastases (BM). We conducted a multi-institutional review of patients with EGFR+ NSCLC treated with upfront osimertinib or osimertinib in combination with RT for new or progressing BM. Our multi-institutional analysis included 128 patients with 714 BM treated between 2013 and 2022. Two BM treatment groups were evaluated: (1) upfront osimertinib alone (n = 66) and (2) osimertinib + RT [whole brain radiation therapy or stereotactic/fractionated radiosurgery (SRS/FSRT)] prior or concurrently with osimertinib (n = 62)]; both groups began treatment within 2 months of BM diagnosis. Time-to-event analysis was conducted with the Kaplan-Meier (KM) method, and outcomes included intracranial control (IC) [both local and distant], intracranial progression free survival (IPFS), and overall survival (OS). A Cox proportional hazards model was utilized for multivariate analysis (MVA). Median follow-up from BM diagnosis was 33.9 months (0.13-76.2 months). No differences in age (p = 0.46), sex (p = 0.72), DS-GPA (p = 0.08), KPS (p = 0.57), number of BM (p = 0.19) or volume of BM (p = 0.45), RT dose (p = 0.45), number of systemic metastases (p = 0.88), and patients symptomatic at presentation (p = 1.0) were noted. Prior treatment of BM was more common in the osimertinib + RT group (50% osimertinib + RT and 27% osimertinib; p = 0.01). The 12-month KM rates for osimertinib vs osimertinib + RT groups for IC were 72% vs 73% (p = 0.33); IPFS 53% vs 66% (p = 0.007); and OS 65% vs 80% (p = 0.025). On MVA, higher KPS (p = 0.002) was associated with increased OS and no extracranial metastasis with increased OS (p = 0.01) and IPFS (p = 0.001). MVA showed no association between osimertinib vs osimertinib + RT for IC, IPFS, or OS. Of the 66 patients treated with upfront osimertinib, 18 patients (27%) with 31 lesions eventually required RT for intracranial progression with the majority 72% being treated with SRS/FSRT at median of 13.5 months (1-22 months) following the start of osimertinib. This study suggests that upfront osimertinib alone may provide sufficient intracranial control to allow RT to be deferred until further intracranial progression in select patients. Prospective trials are warranted to further guide treatment.

PO39: Outcomes of Upfront Radiotherapy in Early Stage Inoperable or Unresectable Endometrial Cancer- An Institutional Analysis

PO39: Outcomes of Upfront Radiotherapy in Early Stage Inoperable or Unresectable Endometrial Cancer- An Institutional Analysis

EPEN-09. UTILITY OF RADIATION THERAPY IN SPINAL CORD MYXOPAPILLARY EPENDYMOMAS: A REVIEW OF THE LITERATURE

Abstract INTRODUCTION Myxopapillary ependymomas (MPEs) are slow-growing tumors that comprise about 25% of spinal ependymomas. Although historically designated as grade 1, the recent WHO classification has upgraded MPEs to grade 2 given their potential for recurrence and dissemination. While the National Comprehensive Cancer Network guidelines recommend avoiding radiation therapy (RT) unless a gross-total resection (GTR) is not achieved, several reports have suggested a potential benefit of adjuvant RT in improving relapse-free survival in children after GTR. This literature review was conducted to compare available data to determine the utility of upfront irradiation in these patients. METHODS A comprehensive literature review from 1984-2021 was performed on PubMed using keywords: “pediatric myxopapillary ependymoma” and “radiation.” One case was censored for unknown radiation status. RESULTS 17 analyses from 1984-2021 were reviewed, yielding 140 pediatric cases of MPE, of whom 59% (n=83) received a GTR. Of those that received a GTR, average age was 13.7 yrs (range, 6-21), and 66% were male. The most common location was lumbosacral (25%), followed by thoracolumbar (19%). 22.8% (n=19) of patients received upfront focal RT. Relapse occurred in eight (42%) patients who received upfront RT, and 30 (47%) of those who did not, with no clear age or gender discrimination in those that relapsed. Distant recurrence occurred in 75% of those who received RT, and 68% of those that did not. The duration of event-free survival will be included in the final presentation. CONCLUSIONS While some individual studies have suggested a survival advantage in pediatric MPE after focal RT, in this meta-analysis, both relapse rate and location seemed similar regardless of receipt of RT. From this available evidence, the efficacy of upfront RT has not been demonstrated.

HGG-28. INTERIM ANALYSIS OF THE GCC1949 PHASE 2 TRIAL USING INDOXIMOD-BASED CHEMO-IMMUNOTHERAPY FOR PATIENTS WITH PEDIATRIC BRAIN TUMORS

Abstract Brain tumors are the leading cause of cancer-related death in children. We report interim results of an ongoing multi-institutional phase 2 trial (NCT04049669) of the IDO pathway-inhibitor indoximod utilized in a chemo-immunotherapy regimen for patients 3-21 years of age with either recurrent malignant brain cancer or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Patients are treated with oral indoximod (38.4 mg/kg/day, divided BID) plus oral temozolomide (200 mg/m2/day for 5 days) in 28-day cycles. Patients for whom radiation therapy is planned as standard-of-care receive indoximod during the up-front radiation regimen. During treatment, palliative radiation, surgery, or dexamethasone are allowed as needed for clinical management. To date, 53 patients have been treated. Estimated median follow-up time was 23 months (range 0.2-35.5 months), and indoximod-based therapy was well tolerated. Estimated median overall survival (OS) was 15 months for the entire mixed population (n= 53, 95%-C.I. 11.5-23.2 months); 23.8 months for recurrent ependymoma (n=26); 13.5 months for recurrent medulloblastoma (n=12); 5.8 months for recurrent glioblastoma/diffuse midline glioma (GBM/DMG, n=9, excludes DIPG); and 9.6 months for newly-diagnosed DIPG (n=6). For the 39 response-evaluable patients to date (those with measurable disease and at least one follow-up MRI on-therapy), objective response in any single lesion by pediatric RANO criteria occurred in 20/39 patients (9/17 ependymoma, 9/11 medulloblastoma, 0/6 GBM/DMG, 2/5 DIPG). Lesion response was associated with significantly better overall survival (estimated median OS 23.2 months, n=20) compared to patients without lesion response (median OS 6.6 months, n=19) (p=0.0005). Single-cell RNA sequencing of serial peripheral blood samples allowed identification of expanded T cell clones, which was correlated with survival. Updated results from the first 53 patients will be presented. These data are replicating results of the preceding phase 1 study (NCT02502708) and provide preliminary evidence of anti-tumor activity in pediatric brain tumors.

ESGO/ESTRO quality indicators for radiation therapy of cervical cancer

BackgroundThe European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort to improve overall quality of care for cervical cancer patients across all aspects, ESGO and the European SocieTy for Radiotherapy and Oncology (ESTRO) initiated the development of quality indicators for radiation therapy of cervical cancer. ObjectiveTo develop a list of quality indicators for radiation therapy of cervical cancer that can be used to audit and improve clinical practice by giving to practitioners and administrators a quantitative basis to improve care and organizational processes, notably for recognition of the increased complexity of modern external radiotherapy and brachytherapy techniques. MethodsQuality indicators were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for identification of potential quality indicators and documentation of scientific evidence, consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians (n = 99). ResultsUsing a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are detailed to define how the quality indicators will be measured in practice. Targets were also defined for specifying the level which each unit or center should be aiming to achieve. Nineteen structural, process, and outcome indicators were defined. Quality indicators 1–6 are general requirements related to pretreatment workup, time to treatment, upfront radiation therapy, and overall management, including active participation in clinical research and the decision making process within a structured multidisciplinary team. Quality indicators 7–17 are related to treatment indicators. Quality indicators 18 and 19 are related to patient outcomes. DiscussionThis set of quality indicators is a major instrument to standardize the quality of radiation therapy in cervical cancer. A scoring system combining surgical and radiotherapeutic quality indicators will be developed within an envisaged future ESGO accreditation process for the overall management of cervical cancer, in an effort to support institutional and governmental quality assurance programs.

Has upfront radiotherapy “come to age” as the standard of care in the management of head and neck squamous cell carcinomas

Has upfront radiotherapy “come to age” as the standard of care in the management of head and neck squamous cell carcinomas

Re-referral for post-op radiation in elderly breast cancer patients who initially omit RT but are unable to tolerate endocrine therapy.

e12507 Background: Omission of Radiation in the setting of Elderly patients 70 yo and above with ER+, cN0, pT1 tumors who receive adjuvant endocrine therapy (HT) is standard of care per NCCN. However, the average adherence rate of HT ranges from 41% to 72%, which is not optimal for patient outcomes. In our institution, we evaluated the treatments of all patients who qualified for omission of radiation upfront and the number of re-referrals for adjuvant radiation in Elderly Breast cancer patients who were unable to tolerate HT past 6 months. Methods: Data was obtained through the National Cancer Registry at our institution for 2021 and reviewed mid 2022. Inclusion criteria included patients diagnosed with Pathologically Invasive Breast Cancer AJCC Stage I-IIB age 70 and above. A total of 176 patients were eligible for review. 86 patients did not qualify for inclusion into study due to 7 receiving surgical treatment outside our system. Furthermore, 81 patients did not qualify due to the following reasons or combination: Mastectomy (19), Triple Negative, Greater than 2 cm, N+, AI only. A total of 90 patients qualified for omission and review. Six month HT therapy cut off was extrapolated by Barbieri et al who determined a 6 month delay of RT after surgery was not associated with an increased risk of relapse. Results: From the 90 patients who qualified for omission of radiation, 67 % (n = 60) of patients chose radiation omission, 30% (n = 27) of patients chose upfront radiation, and 3% (n = 3) of patients declined all therapy. Of the 60 patients who chose omission, 87% of patients had continued HT, however 2 patients passed away within 1 year of surgery. A total of 13% of patients (n = 8) who omitted radiation did not go past 6 months of HT, and only 2 out of 8 patients (25%) were referred back to radiation oncology and moved forward with treatment. For the 27 patients who chose radiation upfront even though they qualified for omission, the most common reason per records was the patient was unsure after initial multidisciplinary clinic that they would be able to tolerate HT. Interestingly, 27% of these patients ended up stopping HT within 9 months due to side effects. Conclusions: Omission of radiation is an option for Elderly Early stage breast cancer patients in the setting of HT. However, HT compliance is variable due to side effects. In our one year single institution study, only 25% of patients who omitted RT and did not get past 6 months of HT were sent back for radiation. We encourage an increased awareness and communication between Radiation Oncology and Medical Oncology regarding the option of radiation for patients who do not pass 6 months of HT. Our institution has implemented an Epic message system and Breast Navigation to aid in re-referral. It is also imperative at the time of Radiation Oncology consultation to discuss the possibility of intolerance to HT in the setting of omission may indicate radiation therapy at a later date.

ESGO/ESTRO quality indicators for radiation therapy of cervical cancer

BackgroundThe European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort...

Can Definitive Radiation Therapy Substitute Surgical Resection in Locally Advanced T3 or T4 Sinonasal Squamous Cell Carcinoma?

This study aimed to compare oncologic outcomes between definitive radiation therapy (RT) and upfront surgical resection in patients with sinonasal squamous cell carcinoma (SCC). Between 2008 and 2021, 155 patients with T1-4b, N0-3 sinonasal SCC were analyzed. The 3-year overall survival (OS), local progression-free survival (LPFS), and overall progression-free survival (PFS) were evaluated using the Kaplan Meier method and compared using a log-rank test. A pattern of regional neck lymph node (LN) failure and treatment-related toxicity profiles were investigated. A total of 63 and 92 patients underwent upfront RT (RT group) and surgical resection (Surgery group), respectively. The RT group included significantly more patients with T3-4 disease than the Surgery group (90.5% vs 39.1%, P < .001). The rates of 3-year OS, LPFS, and PFS in the RT and Surgery groups were 68.6% versus 81.7% (P=.073), 62.3% versus 73.8% (P=.187), and 47.4% versus 66.1% (P=.005), respectively. However, the corresponding rates in patients with T3-4 disease were 65.1% versus 64.8% (P=.794), 57.4% versus 56.8% (P=.351), and 43.2% versus 46.5% (P=.638), respectively, demonstrating no statistically significant differences between the 2 treatment modalities. Among the 133 N0 patients, regional neck LN progression was observed in 17 patients, and the most common sites of regional neck LN failure were ipsilateral levels Ib (9 patients) and II (7 patients). The 3-year neck node recurrence-free rate in cT1-3N0 patients was 93.5%, while that in cT4N0 patients was 81.1% (P=.025). Upfront RT may be considered in selected patients with locally advanced sinonasal SCC, as we have demonstrated similar oncologic outcomes to those of surgery. Prophylactic neck treatment in T4 disease requires further investigation to evaluate its efficacy.

Outcomes of Salvage Therapy for Oropharyngeal Cancer Recurrence Following Upfront Radiation Therapy and Prognostic Factors.

This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment. A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment. After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting. In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.

Brain Metastases: Is There Still a Role for Whole-Brain Radiation Therapy?

Whole-brain radiation therapy (WBRT) has commonly been prescribed to palliate symptoms from brain metastases, to reduce the risk of local relapse after surgical resection, and to improve distant brain control after resection or radiosurgery. While targeting micrometastases throughout the brain can be considered advantageous, the simultaneous exposure of healthy brain tissue might cause adverse events. Attempts to mitigate the risk of neurocognitive decline after WBRT include the selective avoidance of the hippocampi, among others. Besides selective dose reduction, dose escalation to boost volumes, for example, simultaneous integrated boost, aiming at increased tumor control probability is technically feasible. While up-front radiotherapy for newly diagnosed brain metastases often employs radiosurgery or other techniques targeting visible lesions only, sequential (delayed) salvage treatment with WBRT might still become necessary. In addition, the presence of leptomeningeal tumors or very widespread parenchymatous brain metastases might prompt clinicians to prescribe early WBRT.

Conditional Recurrence-Free Survival After Surgical Resection of Meningioma.

Recurrence after meningioma resection warrants serial surveillance imaging, but little evidence guides the optimal time interval between imaging studies/surveillance duration. To describe recurrence-free survival (RFS) after meningioma resection, conditioned to short-term RFS. A retrospective cohort study for adults presenting for meningioma resection from 2000 to 2018 was conducted. The primary outcome was postoperative follow-up RFS. Conditional RFS Kaplan-Meier analysis was performed at 1, 2, 3, 5, and 10 years, conditioned to 6-month and 12-month RFS. RFS probabilities conditioned to 6-month RFS were estimated in subgroups, stratified by World Health Organization grade, extent of resection, and need for postoperative radiation. In total, 723 patients were included. Median age at surgery was 57.4 years (IQR = 47.2-67.2). Median follow-up was 23.5 months (IQR = 12.3-47.8). Recurrence was observed in 90 patients (12%), with median time to recurrence of 14.4 months (IQR = 10.3-37.1). Conditioned to 6-month postoperative RFS, patients had 90.3% probability of remaining recurrence-free at 2 years and 69.4% at 10 years. Subgroup analysis conditioned to 6-month RFS demonstrated grade 1 meningiomas undergoing gross total resection (GTR) had 96.0% probability of RFS at 1 year and 82.8% at 5 years, whereas those undergoing non-GTR had 94.5% and 79.9% probability, respectively. RFS probability was 78.8% at 5 years for non-grade 1 meningiomas undergoing GTR, compared with 69.7% for non-grade 1 meningiomas undergoing non-GTR. Patients with non-grade 1 meningiomas undergoing upfront radiation had a 1-year RFS of 90.1% and 5-year RFS of 51.7%. Recurrence risk after meningioma resection after an initial recurrence-free period is reported, with high-risk subgroups identified. These results can inform objective shared decision-making for optimal follow-up.