Prognostic Factors For Intermediate-Risk Atypical Meningiomas Determining Early Postoperative Adjuvant Radiotherapy Versus Active Monitoring After Gross Total Resection

Background Atypical meningiomas (AMs) constitute 18% of meningiomas. Predictors of recurrence are still indeterminate, and the timing of RT whether to treat with radiation upfront or at initial recurrence remains controversial, especially after gross total resection (GTR). Methods A retrospective study of AMs with uni-and multivariate analyses was conducted with clinical, surgical, radiological, and histopathological parameters. The prognostic factors associated with increased risk of recurrence were elucidated in the whole series and in the subgroup with GTR only. Results Subtotal resection (STR), skullbase-tentorium localization, no adjuvant RT, and progesterone-negativity caused tumor recurrence in 37 patients with a median follow-up of 48 (2-120) months. Among subgroup of 23 patients GTR only, 30.8% showed recurrence in a median of 39.65 months. AMs with a preoperative volume ≥27.5 cm3 disclosed a significantly higher risk of recurrence (a 9.3 fold increase) than those with <27.5 cm3 (66.7% vs. 14.3%, respectively). Skullbase-tentorium localization and progesterone negativity tend to have higher recurrence rates after GTR. Conclusions Preoperative volume was found to be a prognostic factor for AMs with a cut-off value of 27.5 cm3 for the first time in the literature. Our results disclosed that RT could be delayed with active monitorization after GTR for AMs, which are smaller than 27.5 cm3, not localized in skullbase-tentorium and progesterone-positive. Otherwise, early postop RT would be a safer approach without waiting the recurrence for AMs.

Adjuvant radiation versus observation with salvage radiation after gross-total resection of WHO grade II meningiomas: a propensity score–adjusted analysis

OBJECTIVE After gross-total resection (GTR) of a newly diagnosed WHO grade II meningioma, the decision to treat with radiation upfront or at initial recurrence remains controversial. A comparison of progression-free survival (PFS) between observation and adjuvant radiation fails to account for the potential success of salvage radiation, and a direct comparison of PFS between adjuvant and salvage radiation is hampered by strong selection bias against salvage radiation cohorts in which only more aggressive, recurrent tumors are included. To account for the limitations of traditional PFS measures, the authors evaluated radiation failure-free survival (RFFS) between two treatment strategies after GTR: adjuvant radiation versus observation with salvage radiation, if necessary. METHODS The authors performed a retrospective review of patients who underwent GTR of newly diagnosed WHO grade II meningiomas at their institution between 1996 and 2019. They assessed traditional PFS in patients who underwent adjuvant radiation, postoperative observation, and salvage radiation. For RFFS, treatment failure was defined as time from initial surgery to failure of first radiation. To assess the association between treatment strategy and RFFS while accounting for potential confounders, a multivariable Cox regression analysis adjusted for the propensity score (PS) and inverse probability of treatment weighted (IPTW) Cox regression analysis were performed. RESULTS A total of 160 patients underwent GTR and were included in this study. Of the 121 patients who underwent observation, 32 (26.4%) developed recurrence and required salvage radiation. PFS at 3, 5, and 10 years after observation was 75.1%, 65.6%, and 45.5%, respectively. PFS at 3 and 5 years after salvage radiation was 81.7% and 61.3%, respectively. Of 160 patients, 39 received adjuvant radiation, and 3- and 5-year PFS/RFFS rates were 86.1% and 59.2%, respectively. In patients who underwent observation with salvage radiation, if necessary, the 3-, 5-, and 10-year RFFS rates were 97.7%, 90.3%, and 87.9%, respectively. Both PS and IPTW Cox regression models demonstrated that patients who underwent observation with salvage radiation treatment, if necessary, had significantly longer RFFS (PS model: hazard ratio [HR] 0.21, p < 0.01; IPTW model: HR 0.21, p < 0.01). CONCLUSIONS In this retrospective, nonrandomized study, adjuvant radiation after GTR of a WHO II meningioma did not add significant benefit over a strategy of observation and salvage radiation at initial recurrence, if necessary, but results must be considered in the context of the limitations of the study design.

Risk factors for the recurrence of relapsing polychondritis

Background Although the survival rates of relapsing polychondritis (RP) have increased remarkably, the high recurrence rate remains a significant concern for physicians and patients. This retrospective study aimed to investigate the risk factors for RP recurrence. Methods Patients with RP who presented to Kyoto University Hospital from January 2000 to March 2020 and fulfilled Damiani's classification criteria were included. Patients were classified into recurrence and non-recurrence groups. Risk factors for RP recurrence were analysed using a Cox proportional hazards model, and Kaplan–Meier survival curves were drawn. Results Thirty-four patients were included. Twenty-five patients (74%) experienced 64 recurrences (mean: 2.56 recurrences per patients). The median duration before the first recurrence was 202 [55 − 382] days. The median prednisolone dose at the initial recurrence was 10 [5 − 12.75] mg/day. Tracheal involvement was significantly more frequent in the recurrence group at the initial presentation (44.0% vs. 0.0%, p = 0.0172) than in the non-recurrence group, and pre-treatment C-reactive protein levels were significantly high (4.7 vs 1.15 mg/dL, p = 0.0024). The Cox proportional hazards model analysis revealed that tracheal involvement (HR 4.266 [1.535 − 13.838], p = 0.0048), pre-treatment C-reactive protein level (HR 1.166 [1.040 − 1.308], p = 0.0085), and initial prednisolone monotherapy (HR 4.443 [1.515 − 16.267], p = 0.0056) may be associated with recurrence. The median time before the initial recurrence was significantly longer in patients who received combination therapy with prednisolone and immunosuppressants or biologics (400 vs 70 days, p = 0.0015). Conclusions Tracheal involvement, pre-treatment C-reactive protein level, and initial prednisolone monotherapy were risk factors for recurrence in patients with RP. Initial combination therapy with prednisolone and immunosuppressants may delay recurrence.

Permanent Interstitial Cesium-131 Brachytherapy in Treating High-Risk Recurrent Head and Neck Cancer: A Prospective Pilot Study

Purpose/ObjectivesTo establish the feasibility and safety of intraoperative placement of cesium-131 (Cs-131) seeds for re-irradiation in recurrent head and neck cancer (HNC).MethodsPatients with resectable recurrent HNC who were deemed to have a high risk of second recurrence were eligible. Immediately after tumor extirpation, seeds were implanted in the surgical bed based on the preoperative treatment plan with intraoperative adjustment. The surgical bed and the seeds were covered with a regional flap or microvascular free flap. A CT of the neck was obtained on postoperative day 1 for evaluation of the postoperative dose distribution. Patients were followed 1 and 3 months after surgery, then every 3 months in the first 2 years.ResultsFrom November 2016 to September 2018, 15 patients were recruited and 12 patients received treatment per protocol. For the patients who had implants, the sites of initial recurrence included 10 neck alone, 1 neck and larynx, and 1 neck/peristomal. The median follow-up was 21.4 months. After surgery, patients remained hospitalized for a median of 6 days. There were no high-grade toxicities except two patients with wound complications requiring wound care. Eight patients had recurrences, three locoregional alone, three distant alone, and two with both locoregional and distant recurrences. Only one patient had an in-field failure. Five patients died, with 1- and 2-year overall survival of 75 and 58%.ConclusionsCs-131 implant after surgical resection in recurrent HNC is feasible and safe. There were no unexpected severe toxicities. Most failures were out-of-field or distant.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02794675.

O85: ENSURE: EUROPEAN INVESTIGATION OF SURVEILLANCE AFTER RESECTION FOR ESOPHAGEAL CANCER

Presenting Author Email: [email protected] Research question Does intensive postoperative surveillance after planned curative resection for oesophageal cancer lead to increased detection of oligometastatic disease, facilitating increased use of tumor-directed therapy, hence improving overall survival? Background and aim Emerging data demonstrate long-term survival after salvage interventions for local or oligometastatic recurrence following planned curative resection for oesophageal cancer, providing rationale for postoperative surveillance. While meta-analyses confirm the survival benefit of chemotherapy (HR0.81, 0.71-0.92), and HER-2 directed therapy (HR0.75, 0.68-0.84) for patients with recurrent or metastatic oesophageal cancer, the effect of surveillance on oncologic outcome and health-related quality-of-life (HRQL) is unknown. There is currently no international consensus regarding the utility of surveillance following curative-intent treatment for oesophageal cancer, with divergent guidelines from ESMO, AUGIS and NCCN. A pilot study including 27 European centres (ENSURE-1) demonstrated wide variation in practice, with tumour markers, CT and PET-CT utilised in 4 (14.8%), 10 (37.0%) and 3 (11.1%), respectively. This multicenter collaborative project aims to determine the independent impact of intensive surveillance on recurrence patterns, oncologic outcome, and HRQL in survivorship, providing the first adequately powered study to address this critical research question. Patients A retrospective observational study of patients undergoing treatment with curative intent for oesophageal cancer at participating Centers from June 2009 to June 2015. Inclusion criteria 1. Age 18 years and above 2. Underwent surgery with curative intent for cTxNxM0 esophageal or esophagogastric junction (Siewert type I, II and III) cancer 3. Salvage surgery after failure of primary endoscopic or oncologic treatment will be included Exclusion criteria 1. Endoscopic therapy or definitive oncological treatment as sole therapy for esophageal cancer 2. Missing follow-up data Comparator Outcomes will be compared among patients managed with intensive surveillance (IS) compared with standard surveillance. IS will be defined as the routine use of CT/PET-CT for surveillance, at least annually, for at least the first three postoperative years. Each participating centre will be classified as undertaking IS or standard surveillance (SS) according to data submitted in the pilot study (ENSURE-1). Outcomes The primary endpoint of this study is: • Overall survival The secondary endpoints of this study are: • Disease-specific survival • Observed disease-free survival • HRQL o Prespecified EORTC QLQ-C30, QLQ-OG25 items • Recurrence patterns and treatment o Site of disease at initial recurrence o Oligometastatic disease at initial recurrence o Anastomotic disease at initial recurrence o Palliative chemotherapy, chemoradiation and radiation use o Treatment for oligometastatic and anastomotic recurrence (surgery, radiation, chemotherapy only) Study design Power calculation and sample size Power calculations are based on Sisic et al. demonstrating a 5% increase in 5-year overall survival with standardized follow-up in a propensity score matched analysis. Based on an initial feasibility survey of 18 Centers, current estimated number of cases per year for enrolled Centers is 885, therefore it is anticipated that the 5-year study period should capture approximately 4425 patients, of whom 31% undergo high intensity surveillance with cross-sectional imaging, with a minimum postoperative follow-up of 3 years. Using a log-rank analysis to detect a 5% difference in overall survival with sigma of 0.05, with 1371 of 4425 patients in the IS group, the study is powered to 90.4%, while accounting for a potential 20% exclusion rate, the study is powered to 83.1% with current enrolled Centers. Data collection and study definitions Where possible, data will be collected from prospectively maintained databases at participating Centers. Collected data will be entered into a standardized data collection spreadsheet “ENSURE Study - Datasheet” (attached). Variables will be coded at source by Co-Investigators according to standardized coding. Briefly, collected data will include: • Demographics • Co-morbidities and performance status • Histologic type • Tumor location • Clinical stage and grade • Pathologic stage, grade, treatment response and margins • Neoadjuvant therapy details • Operative details • Overall postoperative morbidity • Recurrence and associated treatment • Survival data • HRQOL o ENSURE database will be linked to include relevant HRQL data from a previous study (LASER) Registration The study has been registered on ClinicalTrials.gov (NCT03461341). Statistical Approach Data will be analyzed using SPSS® (v.23.0) software (SPSS, Chicago, IL, USA). For the multivariable analyses, all clinically relevant variables will be inputted into multivariable linear, logistic or Cox proportional hazards regression models. Team and infrastructure An international multidisciplinary collaborative team has been assembled via the Young Investigator Group of the European Society for Diseases of the Esophagus for the conduct of this study, with 27 centres signed up to participate in the pilot study to date. The study will be initiated from St. James's Hospital, Dublin, Ireland; the Karolinska Institute, Stockholm, Sweden; and Imperial College London, London, England. Steering committee: Jessie Elliott (Dublin), Fredrik Klevebro (Stockholm), Sheraz Markar (London), Lucas Goense (Utrecht), Melody Ni (London – statistician), Pernilla Lagergran (Stockholm – HRQL researcher) Supervisory committee: John V Reynolds (Dublin), Magnus Nilsson (Stockholm), George Hanna (London), Giovanni Zaninotto (Padova). Infrastructure: A dedicated biostatistician (Dr Melody Ni, Imperial College London) is a collaborator on the current project and will provide expertise with respect to design and data analysis. A researcher with expertise in HRQL assessment (Professor Pernilla Lagergren, Karolinska Institute) is also a named collaborator on the present project.

Beware of Early Relapse in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy

Purpose: Recurrence patterns in rectal cancer patients treated with preoperative chemoradiotherapy (PCRT) are needed to evaluate for establishing tailored surveillance protocol.Methods: This study included 2,215 patients with locally-advanced mid and low rectal cancer treated with radical resection between January 2005 and December 2012. Recurrence was evaluated according to receipt of PCRT; PCRT group (n = 1,258) and no-PCRT group (n = 957). Early recurrence occurred within 1 year of surgery and late recurrence after 3 years. The median follow-up duration was 65.7 ± 29 months.Results: The overall recurrence rate was similar between the PCRT and no-PCRT group (25.8% vs. 24.9%, P = 0.622). The most common initial recurrence site was the lungs in both groups (50.6% vs. 49.6%, P = 0.864), followed by the liver, which was more common in the no-PCRT group (22.5% vs. 33.6%, P = 0.004). Most of the recurrence occurred within 3 years after surgery in both groups (85.3% vs. 85.8%, P = 0.862). Early recurrence was more common in the PCRT group than in the no-PCRT group (43.1% vs. 32.4%, P = 0.020). Recurrence within the first 6 months after surgery was significantly higher in the PCRT group than in the no-PCRT group (18.8% vs. 7.6%, P = 0.003). Lung (n = 27, 44.3%) and liver (n = 22, 36.1%) were the frequent the first relapsed site within 6 months after surgery in PCRT group.Conclusion: Early recurrence within the first 1 year after surgery was more common in patients treated with PCRT. This difference would be considered for surveillance protocols and need to be evaluated in further studies.

CTNI-13. UPDATES ON CLINICAL OUTCOMES AND TUMOR RECURRENCE PATTERNS OF A HUMAN PILOT STUDY ASSESSING EFFICACY OF BELINOSTAT (PXD-101) COMBINING WITH CHEMORADIATION IN TREATING GLIOBLASTOMA

INTRODUCTION Glioblastoma (GBM) is highly aggressive with poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability that has anti-GBM activity and may enhance effects of chemoradiation. Our institution conducted a clinical trial evaluating clinical efficacy of belinostat with standard-of-care therapy for GBMs. METHODS 13 and 14 patients were enrolled into cohort 1 (c1, control) or cohort 2 (c2, belinostat) with 12 in each group with sufficient follow-up MRIs for recurrence analysis. All patients received concurrent, adjuvant temozolomide and focal radiation therapy (RT). For c2 patients, the belinostat regimen (500-750mg/m2 1x/day x 5 days) was given over three cycles every 3 weeks (weeks -1, 2, and 5 of RT). RT margins of 5–10 mm and 3 mm were added to generate clinical tumor volumes and planning target volumes (PTVs). PTV1 (based on FLAIR MRI) and PTV2 (based on CE-T1w MRI) received 51 and 60 Gy, respectively, over 30 fractions. Volume at initial recurrence (rGTV) was contoured. RESULTS Mean age was 58.3 years for c1 and 51.1 years for c2. Patient/tumor characteristics were similar between cohorts. Median OS were 16.6 and 18.5 months for c1 and c2 (p=0.538), respectively. Average minimum, maximum and mean radiation dose to rGTV was 54.1 Gy, 64.2 Gy and 62 Gy, for c1, and 47.5 Gy, 57.6 Gy and 53.5 Gy, for c2 (p=0.322, 0.088 and 0.071), respectively. The mean overlap between rGTV and PTV1/PTV2 for c1 & c2 were 99.2% & 96.9%/99.8% & 78.7% (p=0.489/0.133), respectively. CONCLUSION Median OS was slightly longer for c2 though not statistically significant. rGTV in c1 received higher radiation doses and had more overlap with PTV2 than in c2. Out-of-field recurrence appears more likely in c2 suggesting better infield control with belinostat. This study highlights the potential of belinostat as a synergistic therapeutic agent for GBM treatment.