Analysis Of Recurrence Patterns Research Articles

Repeated HyperArc radiosurgery for recurrent intracranial metastases and dosimetric analysis of recurrence pattern to account for diffuse dose effect on microscopical disease

AimsEvaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods56 patients were treated for 702 BMs with 197 (range 2–8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). ResultsThe 1-year OS was 70 %, and the median was 20.8 months (17–36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0–7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. ConclusionIntracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

Impact of Urethra-Preserving Surgery During Radical Cystectomy: An Optimal Urethral Management in the Robotic Era

ObjectivesThe optimal indication and survival benefits of prophylactic urethrectomy (PU) during radical cystectomy remain unclear. Therefore, this study aims to evaluate the impact of urethra-preserving surgery (UPS) on oncological outcome including its recurrence patterns, and to establish an optimal urethral management strategy with a novel UPS technique in the robotic era. Patients and methodsWe retrospectively analyzed 281 male patients with bladder cancer who received radical cystectomy (RC) (115 with and 166 without PU) at our institutions between 2010 and 2023. Subsequently, perioperative and oncological outcomes were assessed between propensity score-matched cohorts. ResultsUrethral recurrence (UR) occurred in 5 patients (5/166, 3.0%), all of whom underwent open-RC. Three among those (1.8%) with concomitant metastasis were died of cancer. There were no statistically significant differences between the PU and UPS groups in urethral-recurrence free survival (urethral-RFS) (P = .14), local-RFS (P = .59) and overall survival (OS) (P = .84) in the entire cohort. However, the UPS group showed significantly worse urethral-RFS (P = .008), local-RFS (P = .005) and OS (P = .03) in patients with high-risk of UR. Analysis of recurrence patterns revealed that UPS in high-risk patients significantly increased local recurrence (25.8% vs. 5.0%, P = .02). Conversely, a novel robotic-UPS technique demonstrated significantly favorable perioperative outcomes, comparable local-RFS (P = .79) and OS (P = .16) without UR (0/134, 0%) when compared to robotic-PU. Robotic-UPS also exhibited significantly better local-RFS (P =.007) and OS (P < .001) than open-UPS. ConclusionsUR-related death was rare and PU did not show a survival benefit for the entire cohort. However, inappropriate UPS in patients at high-risk of UR may increase local recurrence which might be responsible for poor survival after UPS rather than disease progression derived from UR. The robotic-UPS has the potential to reduce unnecessary PU, urethral and local recurrence without compromising survival.

Pattern of recurrence after stereotactic body radiotherapy of nodal lesions: a single-institution analysis.

Stereotactic body radiotherapy (SBRT) and/or single fraction stereotactic body radiosurgery (SRS) are effective treatment options for the treatment of oligometastatic disease of lymph nodes. Despite the encouraging local control rate, progression-free survival remains unfair due to relapses that might occur in the same district or at other sites. The recurrence pattern analysis after nodal local ablative RT (laRT) in oligometastatic patients is presented in this study. The pattern of failure of patients with nodal metastases who were recruited and treated with SBRT in the Destroy-1 or SRS in the Destroy-2 trials was investigated in this single-institution, retrospective analysis. The different relapsed sites following laRT were recorded. Data on 190 patients who received SBRT or SRS on 269 nodal lesions were reviewed. A relapse rate of 57.2% (154 out of 269 nodal lesions) was registered. The pattern of failure was distant in 88 (57.4%) and loco-regional in 66 (42.6%) patients, respectively. The most frequent primary malignancies among patients experiencing loco-regional failure were genitourinary and gynaecological cancers. Furthermore, the predominant site of loco-regional relapse (62%) was the pelvic area. Only 26% of locoregional relapses occurred contra laterally, with 74% occurring ipsilaterally. The recurrence rates after laRT for nodal disease were more frequent in distant regions compared to locoregional sites. The most common scenarios for locoregional relapse appear to be genitourinary cancer and the pelvic site. In addition, recurrences often occur in the same nodal station or in a nodal station contiguous to the irradiated nodal site. Local ablative radiotherapy is an effective treatment in managing nodal oligometastasis. Despite the high local control rate, the progression free survival remains dismal with recurrences that can occur both loco-regionally or at distance. To understand the pattern of failure could aid the physicians to choose the best treatment strategy. This is the first study that reports the recurrence pattern of a significant number of nodal lesions treated with laRT.

Comparison of different target volume delineation strategies based on recurrence patterns in adjuvant radiotherapy for glioblastoma.

Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) recommendations are commonly used guidelines for adjuvant radiotherapy in glioblastoma. In our institutional protocol, we delineate T2-FLAIR alterations as gross target volume (GTV) with reduced clinical target volume (CTV) margins. We aimed to present our oncologic outcomes and compare the recurrence patterns and planning parameters with EORTC and RTOG delineation strategies. Eighty-one patients who received CRT between 2014 and 2021 were evaluated retrospectively. EORTC and RTOG delineations performed on the simulation computed tomography and recurrence patterns and planning parameters were compared between delineation strategies. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for statistical analyses. Median overall survival and progression-free survival were 21 months and 11 months, respectively. At a median 18 month follow-up, of the 48 patients for whom recurrence pattern analysis was performed, recurrence was encompassed by only our institutional protocol's CTV in 13 (27%) of them. For the remaining 35 (73%) patients, recurrence was encompassed by all separate CTVs. In addition to the 100% rate of in-field recurrence, the smallest CTV and lower OAR doses were obtained by our protocol. The current study provides promising results for including the T2-FLAIR alterations to the GTV with smaller CTV margins with impressive survival outcomes without any marginal recurrence. The fact that our protocol did not result in larger irradiated brain volume is further encouraging in terms of toxicity.

Non-endometrioid endometrial cancer: analysis of recurrence pattern and identification of prognostic and treatment factors affecting recurrence and survival.

We investigated the characteristics of recurrence pattern and survival of patients with non-endometrioid endometrial cancer (NEEC) and attempted to identify prognostic and treatment factors affecting disease-free survival (DFS) and overall survival (OS) of these patients. Fifty-seven patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVA NEEC from February 2003 to December 2021 were retrospectively analyzed. The 5‑year DFS and OS rates of the total cohort were 50.6% and 56.1%, respectively. Recurrence occurred in 28patients (49.1%) during follow-up, and the most common recurrence pattern was distant metastasis (DM; 78.6% of total recurrences). The occurrence of relapse significantly reduced 5‑year OS (recurrence group vs. non-recurrence group: 12.5% vs. 100%; p < 0.001). In univariate analysis, adjuvant radiotherapy (RT) group showed significantly higher 5‑year DFS (56.7% vs. 37.9%; p = 0.04), local recurrence-free survival (91.6% vs. 50.5%; p = 0.01), and regional recurrence-free survival (88.2% vs. 56.5%; p < 0.01) than the non-RT group. In multivariate analysis, advanced FIGO stage was identified as anegative prognostic factor for DFS and OS. Lymphovascular space invasion (LVSI) and adjuvant RT were independent prognostic factors for DFS. The most common recurrence pattern observed in patients with NEEC was DM. FIGO stage and LVSI were identified as prognostic factors for survival, and RT was identified as atherapeutic modality that could increase DFS. To improve the OS of patients with NEEC, the addition of effective chemotherapy that can reduce DM may be important.

Observation of the delineation of the target volume of radiotherapy in adult-type diffuse gliomas after temozolomide-based chemoradiotherapy: analysis of recurrence patterns and predictive factors

BackgroundRadiation therapy is the cornerstone of treatment for adult-type diffuse gliomas, but recurrences are inevitable. Our study assessed the prognosis and recurrence pattern of different radiotherapy volumes after temozolomide-based chemoradiation in our institution.MethodsThe treatment plans were classified into two groups, the plan 1 intentionally involved the entire edema area while plan 2 did not. Retrospectively investigate the differences in outcomes of 118 adult-type diffuse gliomas patients between these two treatment plans. Then, patients who underwent relapse were selected to analyze their recurrence patterns. Continuous dynamic magnetic resonance images (MRI) were collected to categorized the recurrence patterns into central, in-field, marginal, distant, and cerebrospinal fluid dissemination (CSF-d) recurrence. Finally, the clinical and molecular characteristics which influenced progression were analyzed.ResultsPlan 1 (n = 63) showed a median progression-free survival (PFS) and overall survival (OS) of 9.5 and 26.4 months while plan 2 (n = 55) showed a median PFS and OS of 9.4 and 36.5 months (p = 0.418; p = 0.388). Treatment target volume had no effect on the outcome in patients with adult-type diffuse gliomas. And there was no difference in radiation toxicity (p = 0.388). Among the 90 relapsed patients, a total of 58 (64.4%) patients had central recurrence, 10 (11.1%) patients had in-field recurrence, 3 (3.3%) patients had marginal recurrence, 11 (12.2.%) patients had distant recurrence, and 8 (8.9%) patients had CSF-d recurrence. By treatment plans, the recurrence patterns were similar and there was no significant difference in survival. Reclassifying the progression pattern into local and non-local groups, we observed that oligodendroglioma (n = 10) all relapsed in local and no difference in PFS and OS between the two groups (p > 0.05). Multivariable analysis showed that subventricular zone (SVZ) involvement was the independent risk factor for non-local recurrence in patients with GBM (p < 0.05).ConclusionIn our study, deliberately including or not the entire edema had no impact on prognosis and recurrence. Patients with varied recurrence patterns had diverse clinical and genetic features.

Analysis of recurrence probability following radiotherapy in patients with CNS WHO grade 2 meningioma using integrated molecular-morphologic classification.

The current World Health Organization (WHO) classification of brain tumors distinguishes 3 malignancy grades in meningiomas, with increasing risk of recurrence from CNS WHO grades 1 to 3. Radiotherapy is recommended by current EANO guidelines for patients not safely amenable to surgery or after incomplete resection in higher grades. Despite adequately predicting recurrence probability for the majority of CNS WHO grade 2 meningioma patients, a considerable subset of patients demonstrates an unexpectedly early tumor recurrence following radiotherapy. A retrospective cohort of 44 patients with CNS WHO grade 2 meningiomas were stratified into 3 risk groups (low, intermediate, and high) using an integrated morphological, CNV- and methylation family-based classification. Local progression-free survival (lPFS) following radiotherapy (RT) was analyzed and total dose of radiation was correlated with survival outcome. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities were further assessed. Risk stratification of CNS WHO grade 2 meningioma into integrated risk groups demonstrated a significant difference in 3-year lPFS following radiotherapy between the molecular low- and high-risk groups. Recurrence pattern analysis revealed that 87.5 % of initial relapses occurred within the RT planning target volume or resection cavity. Integrated risk scoring can identify CNS WHO grade 2 meningioma patients at risk or relapse and dissemination following radiotherapy. Therapeutic management of CNS WHO grade 2 meningiomas and future clinical trials should be adjusted according to the molecular risk-groups, and not rely on conventional CNS WHO grading alone.

Can Retroperitoneal Lymph Node Dissection (RPLND) be feasibly performed to prolong survival in Renal Cell Carcinoma (RCC) with limited lymph node involvement? An Analysis of Recurrence Patterns.

The therapeutic benefit of performing a lymph node dissection (LND) in patients with renal cell carcinoma (RCC) has been controversial. In prior studies, it was thought that a low event rate for nodal metastases affected the ability to draw any conclusions. Here, we opted to select patients that had low burden 1 or 2 nodes positive to study survival outcomes and recurrence patterns based on limited LND or extended LND with a template retroperitoneal lymph node dissection (RPLND). We used our single institutional database from 2000 and 2019 and identified 45 patients that had only 1 or 2 nodes positive on final pathology without any other systemic disease. These patients all underwent nephrectomy with limited LND or a template RPLND on the ipsilateral side. We identified 23 patients in the limited LND and 22 in the template RPLND group. Thirty-one patients included in the study had 1 positive lymph node and 14 patients had 2 positive lymph nodes. For patients undergoing a limited LND, a median 4 (IQR 1-11) lymph nodes were resected and for those undergoing template RPLND, 18 (IQR: 13-23) lymph nodes were resected. On Kaplan-Meier analysis, a difference was noted in overall survival (P = 0.04) when comparing limited LND to template RPLND. We also mapped out patterns of recurrence and found that 6 patients had retroperitoneal lymph node recurrences after a limited LND in the ipsilateral node packet. On univariate analysis, pathologic stage was a major factor for survival, but did not remain as significant with the inclusion of template RPLND status and Charlson Comorbidity Index in multivariate analysis. We identified specific patients that had RCC with limited lymph node involvement. We found that a select number of patients had durable improvement in survival outcomes with template RPLND. In examining the recurrence patterns, a greater number of patients may have derived benefit for an initial template RPLND.

Value of the Preoperative D-Dimer to Albumin Ratio for Survival and Recurrence Patterns in Gastric Cancer.

D-dimer (DDI) and albumin are prognostic markers for numerous cancers; however, the predictive value of the preoperative DDI-to-albumin ratio (DAR) on the survival and recurrence patterns of gastric cancer (GC) remains unclear. The aim of this study was to explore the prognostic value of the DAR in GC. Our study included 1766 patients with GC, divided into training and testing cohorts at a ratio of 7:3. Patients were classified into either a high-DAR group (> 0.0145) or low-DAR group (≤ 0.0145) according to the cut-off value of receiver operating characteristic (ROC) curve analysis. The relationship between the DAR and recurrence pattern was analyzed in stage II/III patients. Eight preoperative hematological factors were included and 17 composite inflammatory markers were constructed. ROC and random forest analyses indicated that among 17 markers, DAR was the best predictor for overall survival (OS) in GC (p<0.01). High DAR was significantly associated with poor OS (hazard ratio [HR] 1.89, p<0.001) and recurrence-free survival (RFS; HR 1.85, p<0.001). Subgroup analysis showed no differences in OS and RFS between the high- and low-DAR groups in stage I or pT1/2 or pN0/1 patients; however, in stage II/III or pT3/4 or pN2/3 patients, the high-DAR group had shorter OS and RFS rates than the low-DAR group (p<0.001). Similar results were found in the testing cohort. According to the multivariate analysis based on the training cohort, five indices, including DAR, cT stage, cN stage, age and body mass index (BMI), were incorporated to establish a nomogram model to predict the long-term prognosis of GC. The model showed comparable forecast performance in predicting OS (C-index: 0.773 vs. 0.786) and RFS (C-index: 0.788 vs. 0.795) compared with pTNM. Recurrence pattern analysis in stage II/III patients showed that the high-DAR group had a higher incidence of peritoneal implantation and early recurrence (ER) than the low-DAR group, and the post-recurrence survival in the high-DAR group was significantly shorter than that in the low-DAR group (p=0.016). The preoperative DAR is a new biomarker for the long-term survival prediction of GC. In advanced GC, a preoperative DAR > 0.0145 aids the timely detection of ER and peritoneal recurrence after surgery, thus guiding individual follow-up strategies.

What Neoadjuvant Radiation Volumes Should be Covered in Pancreas Cancer? An Analysis of Recurrence Patterns among Tumors with Arterial vs. Venous Involvement

<h3>Purpose/Objective(s)</h3> In Pancreatic ductal adenocarcinoma (PDAC) candidates for neoadjuvant therapy followed by surgical resection, it is not clear whether there is difference in failure outcome between arterial and venous involvement subgroups, and which group benefits from neoadjuvant stereotactic ablative radiation (NA SABR). We hypothesize that: 1-loco-regional failure (LRF) is higher for arterial vs venous involved PDAC, 2- NA SABR decreases LRF in arterial involved PDAC, 3- LRFs in patients who received neoadjuvant chemotherapy (NA CTH) only can be used to propose a NA SABR radiation planning volume. <h3>Materials/Methods</h3> We reviewed our institutional database for patients with the following criteria: 1- histopathological diagnosis of PDAC, 2- tumors with vessel involvement at baseline, and 3- received neoadjuvant therapy followed by surgical resection. Vessel involvement was stratified on baseline CT scan with IV contrast to either arterial (Celiac artery (CA), superior mesenteric artery (SMA), and common hepatic artery) or venous involvement (Portal and Superior mesenteric vein). LRF was defined as new lesion(s) following surgical resection in remnant pancreas, surgical bed, pancreatojejunostomy site, CA, SMA, and regional nodes. SABR was defined as 5 fraction radiation under image guidance. To address the hypothesis: 1- in NA CTH only cohort, we compared LRF events in arterial vs venous involvement using log rank test, 2- in patients with arterial involvement, we used log rank test to compare LRF events in NA SABR+NA CTH versus NA CTH only, 3- in patients who received NA CTH only, with arterial involvement and developed LRF, we did a soft tissue imaging fusion using CA and SMA of all failure scans to baseline CT scans. The distance along the SMA that was involved by LRFs was measured along the y axis. <h3>Results</h3> Fifty-seven patients met the inclusion criteria with a median follow up of 31 months. Thirty-one patients received NA CTH only, while 26 patients received NA SABR plus chemotherapy. Among the NA CTH only cohort (n=31), 7 and 24 patients presented with arterial and venous involvement respectively. Among the NA SABR cohort (n=26), 22 and 4 patients presented with arterial and venous involvement respectively. 1- among NA CTH only cohort (n=31), one-year LRF free was 35.7% in arterial involvement vs 75.5 % in venous involvement (HR= 7.7, 95 % CI 1.8-32.8, p value=0.0059), 2- among patients with arterial involvement (n=29), the one-year LRF was 73.8% in SABR treated compared to 35.7 % in non SABR treated (HR= 5.3, 95 % CI 1.3 to 21, p value=0.0187), 3- we propose low and high dose volumes from the NA CTH that we aim to validate independently. The volume of combined LRFs was 102.2 cc. The distance along the SMA to be covered during planning was 5.7 cm along the y axis. Median distance from tumor artery contact to the LRFs was 1.2 and 1.7 cm in the superior and inferior directions respectively. <h3>Conclusion</h3> NA SABR may decrease LRF in arterial involved PDAC. LRFs in non SABR treated cohort can guide radiation planning volumes.

Clinical assessment of T2 papillary thyroid carcinoma: a retrospective study conducted at a single tertiary institution

The extent of surgery among patients with T2 papillary thyroid carcinoma (PTC) remains controversial. Thus, we herein aimed to evaluate the risk factors for recurrence, particularly based on the extent of surgery, among patients with T2 PTC at a single tertiary institution. We assessed 251 patients who underwent thyroid surgery for T2 PTC from January 2009 to December 2014 at Seoul St. Mary’s Hospital (Seoul, Korea). The mean follow-up duration was 100.7 months. Eleven (4.4%) patients had recurrence. The recurrence rates did not significantly differ in terms of the extent of surgery (p = 0.868). Patients with a high lymph node ratio (LNR) had a significantly higher recurrence rate than those with a low LNR (p < 0.001). According to a recurrence pattern analysis, five of six patients in the lobectomy group had recurrence in the ipsilateral lateral compartment. A multivariate analysis revealed that a high LNR was a significant risk factor for recurrence (hazard ratio: 11.025, p = 0.002). Our results suggest that patients without clinical evidence of any lymph node metastases and those with limited lesions in the thyroid gland can undergo lobectomy and LNR can serve as an independent risk factor for predicting recurrence in T2 PTC.

Metastasis-Free Survival and Patterns of Distant Metastatic Disease After Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA-PET)-Guided Salvage Radiation Therapy in Recurrent or Persistent Prostate Cancer After Prostatectomy

Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is increasingly used to guide salvage radiation therapy (sRT) in patients with prostate cancer and biochemical recurrence/persistence after prostatectomy. This work examined (1) metastasis-free survival (MFS) after PSMA-PET guided sRT and (2) the metastatic patterns on PSMA-PET images after sRT. This retrospective, multicenter (9 centers, 5 countries) study included patients referred for PSMA-PET due to recurrent/persistent disease after prostatectomy. Patients with distant metastases (DM) on PSMA-PET before sRT were excluded. Cox regression was performed to assess the effect of clinical parameters on MFS. The distribution of PSMA-PET detected DM after sRT and their respective risk factors were analyzed. All (n = 815) patients received intensity modulated RT to the prostatic fossa. In the case of PET-positive pelvic lymph nodes (PLN-PET) (n = 275, 34%), pelvic lymphatics had been irradiated. Androgen deprivation therapy had been given in 251 (31%) patients. The median follow-up after sRT was 36 months. The 2-/4-year MFS after sRT were 93%/81%. In multivariate analysis, the presence of PLN-PET was a strong predictor for MFS (hazard ratio, 2.39; P < .001). After sRT, DM were detected by PSMA-PET in 128/198 (65%) patients, and 2 metastatic patterns were observed: 43% had DM in sub-diaphragmatic para-aortic LNs (abdominal-lymphatic), 45% in bones, 9% in supra-diaphragmatic LNs, and 6% in visceral organs (distant). Two distinct signatures with risk factors for each pattern were identified. MFS in our study is lower compared with previous studies, obviously due to the higher detection rate of DM in PSMA-PET after sRT. Thus, it remains unclear whether MFS is a surrogate endpoint for overall survival in PSMA PET-staged patients in the post-sRT setting. PLN-PET may be proposed as a new surrogate parameter predictive of MFS. Analysis of recurrence patterns in PET after sRT revealed risk factor signatures for 2 metastatic patterns (abdominal-lymphatic and distant), which may allow individualized sRT concepts in the future.

SYST-07. PILOT STUDY UTILIZING THE HDAC INHIBITOR BELINOSTAT WITH CHEMORADIATION FOR NEWLY-DIAGNOSED GLIOBLASTOMA

Abstract PURPOSE Glioblastomas (GBMs) are highly aggressive brain tumors with poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability, anti-GBM activity, and potential to enhance chemoradiation. This clinical trial sought to determine a tolerable dose of concurrent belinostat and assess the clinical efficacy of combining this drug with standard-of-care therapy. METHODS 13 patients each were enrolled in control and belinostat cohorts. The belinostat cohort was given a belinostat regimen (500-750mg/m2 1x/day x 5 days) every 3 weeks (weeks 0, 3, and 6 of RT). All patients received standard temozolomide and radiation therapy (RT). Patient outcomes included progression-free survival, overall survival (OS), and analysis of recurrence pattern of the recurrent gross tumor volume (rGTV). RESULTS Belinostat at 750 mg/m2 produce dose-limiting toxicities (DLTs) in 2 of 3 patients while belinostat at 500 mg/m2 did not result in DLTs. Median OS was 18.5 months for the belinostat cohort and 15.8 months for the control cohort (p=0.53). The rGTVs in the control cohort occurred in areas that received higher radiation doses than that in the belinostat cohort. For those belinostat patients that experienced out-of-field recurrences, tumors were detectable by spectroscopic MRI (sMRI) before RT. In particular, one belinostat patient had an IDH-mutant GBM that had an extraordinary response to therapy with significant shrinkage of enhancing tumor much greater than expected. CONCLUSION Belinostat given concurrently at 500 mg/m2 is well-tolerated. While median OS was not significantly increased for the belinostat cohort, recurrence analysis suggests better in-field control with belinostat, suggesting a radio-sensitizing effect. This study suggests that belinostat can act as a synergistic therapeutic agent for GBMs that may be further enhanced by sMRI-guided RT and may be particularly effective against IDH mutant tumors. A trial is currently in development using belinostat with sMRI-guided RT for IDH-mutant high-grade gliomas.

Retrospective analysis of recurrence patterns and clinical outcome of grade II meningiomas following postoperative radiotherapy

BackgroundAtypical meningiomas exhibit a high tendency for tumor recurrence even after multimodal therapy. Information regarding recurrence patterns after additive radiotherapy is scarce but could improve radiotherapy planning and therapy decision. We conducted an analysis of recurrence patterns with regard to target volumes and dose coverage assessing target volume definition and postulated areas of tumor re-growth origin. Prognostic factors contributing to relapse were evaluated.MethodsThe clinical outcome of patients who had completed additive, somatostatin receptor (SSTR)-PET/CT-based fractionated intensity-modulated radiotherapy for atypical meningioma between 2007 and 2017 was analyzed. In case of tumor recurrence/progression, treatment planning was evaluated for coverage of the initial target volumes and the recurrent tumor tissue. We proposed a model evaluating the dose distribution in postulated areas of tumor re-growth origin. The median of proliferation marker MIB-1 was assessed as a prognostic factor for local progression and new distant tumor lesions.Results Data from 31 patients who had received adjuvant (n = 11) or salvage radiotherapy (n = 20) were evaluated. Prescribed dose ranged from 54.0 to 60.0 Gy. Local control at five years was 67.9%. Analysis of treatment plans of the eight patients experiencing local failure proved sufficient extent of target volumes and coverage of the prescribed dose of at least 50.0 Gy as determined by mean dose, D98, D2, and equivalent uniform dose (EUD) of all initial target volumes, postulated growth-areas, and areas of recurrent tumor tissue. In all cases, local failure occurred in high-dose volumes. Tumors with a MIB-1 expression above the median (8%) showed a higher tendency for re-growth.ConclusionsThe model showed adequate target volume and relative dose distribution but absolute dose appears lower in recurrent tumors without reaching statistical significance. This might provide a rationale for dose escalation studies. Biological factors such as MIB-1 might aid patients’ stratification for dose escalation.

Recurrence Following Neoadjuvant Therapy and Resection for Pancreatic Ductal Adenocarcinoma: A Comprehensive Meta-Analysis and Meta-Regression

Background: This review aims to provide a comprehensive analysis of recurrence patterns in patients undergoing neoadjuvant therapy (NAT) in comparison to those undergoing up-front surgery (US) for PDAC. Methods: The EMBASE, SCOPUS, PubMed and Cochrane library databases were systematically searched to identify eligible comparative studies. The primary outcome was time to first recurrence and location of recurrence. Results: Twenty-five articles were identified including 4822 patients undergoing resection. The weighted mean follow-up interval for recurrence outcomes was 40.8months (CI 33.4-48.1). The weighted mean overall recurrence rate was 63.4% (CI 51.8-73.%) for NAT, significantly lower than the 74% (CI 68.7-80%) weighted overall recurrence rate of the US cohort (OR 0.67 (CI 0.52-0.87), P=0.006). NAT was also associated with a significantly longer weighted mean time to first recurrence (NAT 18.8months US 15.7months, P=0.015). The weighted locoregional recurrence (NAT 12%, US 27%, P=0.004) and liver recurrence (NAT 19.4%, US 30.1% P=0.023) rates were markedly improved among NAT patients. Weighted lung and peritoneal recurrence rates did not differ (P=0.705 and P=0.549 respectively). NAT was further associated with a greater two- (NAT 39%, US 22% OR 1.84 (CI 1.22-2.78), P=0.007) and five-year (NAT 24%, US 13% OR 1.95 (CI 1.03-3.69), P=0.043) recurrence free survival. Borderline resectability, presence of perineural invasion and a lower N0 nodal status were positive predictors of overall recurrence in the NAT cohort. Conclusions: NAT is associated with improved overall recurrence rates and longer time to first recurrence, an observation likely attributed to the improved rates of locoregional and liver recurrence.

356MO Osimertinib adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence

CNS relapse is common in NSCLC, and is a poor prognostic factor. In the resected EGFRm NSCLC setting, the impact of treatment on sites of recurrence, including the CNS, is a key consideration. Osimertinib is a 3rd-generation EGFR-TKI with demonstrated efficacy in NSCLC CNS metastases. In ADAURA, osimertinib demonstrated a highly statistically significant and clinically meaningful improvement in disease-free survival vs placebo (PBO; DFS, hazard ratio [HR]: 0.20 [99.12% CI 0.14, 0.30; p<0.001) in resected stage IB–IIIA EGFRm (ex19del/L858R) NSCLC (Ph III ADAURA; NCT02511106). We report an exploratory analysis of recurrence patterns. Pts with resected stage IB–IIIA EGFRm NSCLC, with/without adjuvant chemotherapy, were randomised 1:1 to receive osimertinib 80 mg once-daily or PBO until recurrence/discontinuation/3 years. Patterns of recurrence and CNS DFS (time to CNS recurrence/death) were exploratory endpoints. An MRI/CT brain scan was mandated at baseline either before surgery or upon enrolment, but was not required in absence of symptoms. Recurrence was categorised as local/regional and/or distant, with sites of relapse recorded. Data cutoff: 17/01/20. Overall, 682 pts were randomised (osimertinib: 339; PBO: 343). Pts treated with osimertinib had fewer recurrence events vs PBO (Table); 45 pts had CNS DFS events (osimertinib: 6; PBO: 39; median follow-up 22 months [mo]). Conditional probability of CNS recurrence at 12 mo (95% CI): <1% (0%, 2%) with osimertinib vs 7% (4%, 10%) with PBO. Median CNS DFS: not reached (95% CI 39.0 mo, not calculable [NC]) with osimertinib vs 48.2 (NC, NC) mo with PBO. CNS DFS HR: 0.18 (95% CI 0.10, 0.33); p<0.0001.Table: 356MOOsimertinib n=339PBO n=343CNS DFS events, pts (%):6 (2)39 (11)CNS recurrence4 (1)33 (10)Death*2 (1)6 (2)DFS events, pts (%):37 (11)159 (46)Disease recurrence37 (11)157 (46)—— Non-CNS recurrence33 (10)123 (36)—— CNS recurrence4 (1)33 (10)—— Disease recurrence with missing location01 (0)Death†02 (1)*Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data. †Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data. Open table in a new tab *Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data. †Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data. There was a clinically meaningful improvement in CNS DFS with osimertinib: 82% reduction in risk of CNS disease recurrence or death. Results support that osimertinib reduces risk of CNS recurrence in the resected EGFRm NSCLC setting.

Oncological outcome and recurrence pattern analysis after involved-field irradiation in combination with rituximab for early-stage nodal and extranodal follicular lymphoma

PurposeCombined radioimmunotherapy (RIT) in follicular lymphomas (FL) has shown promising treatment efficacy in the Mabthera® and Involved field Radiation (MIR) study. Aim of this study was to analyze treatment efficacy and recurrence patterns after RIT in early-stage nodal and extranodal FL.MethodsWe reviewed 107 patients who were treated with combined RIT in two centers. Treatment consisted of 4 × rituximab followed by RIT with 4 × rituximab and involved field (IF) radiotherapy with 30/40 Gy. Median follow-up period was 71 months. In contrast to the MIR study, extranodal involvement and grade 3A histology were included in the analysis.ResultsExtranodal involvement and grade 3A histology were present in 21.8% and 13.1%, respectively. Overall response rate (ORR) after 4 × rituximab, after completion of RIT, and after 6 months was 78.1%, 98.8%, and 98.8%, respectively, with increasing rates of complete remissions (CR). Predictive factors associated with superior PFS were tumor size, completely excised lymphomas, and response to first 4 × rituximab. 5‑year PFS rate was 87.3%, with mostly outfield recurrences (94.1%). Second-line treatment was effective, with 53.3% CR and 46.7% partial remissions (PR). 5‑year OS was 98.1%. RIT was tolerated well, with mainly grade 1–2 acute side effects.ConclusionThe real-world efficacy of RIT is comparable with the results of the MIR study. Additionally, this analysis shows that extranodal involvement and grade 3A histology are not associated with inferior PFS.

Analysis of local recurrence pattern for limited stage small cell lung cancer after IMRT plus chemotherapy

Objective To investigate localized regional recurrence after chemotherapy and chest radiotherapy in limited stage small cell lung cancer (LS-SCLC), and explore the relationship between recurrence location and radiotherapy and chemotherapy and its influencing factors. Methods From 2006 to 2014, pathological LS-SCLC treated in CAMS, 125 patients had local recurrence, Kaplan-Meier statistical method was used to analyze the survival rate and PFS of each recurrence site. Log-rank was used to compare the survival rate of each group. Univariate analysis includes Chi-squareand t-test for the factors for the recurrence site. Multivariate analysis using Logistic regression. Results The 1-, 2-and 5-year overall survival rates were 92.0%, 46.4% and 14.7%, respectively. The median progression time was 12.96 months, The median survival time after progression was 11.5 months, and the 1-, 2-, and 5-year overall survival rates were 45.0%, 23.0%, and 10.0%, respectively. The recurrence sites include intrapulmonary recurrence (67 patients), regional lymph nodes (21 patients), simultaneous intrapulmonary and regional lymph nodes (28 patients), and contralateral or supraclavicular lymph nodes (9 patients). The median survival time were 23.96 months, 24.76 months, 23.23 months, and 18.66 months, and the 2-year survival rates were 49%, 52%, 46%, and11%, respectively (P=0.000, 0.004, 0.008). In 6 patients (4.0%), 5 patients were located in the supraclavicular region, and 1 patient (0.8%) in the field. Conclusions For LS-SCLC undergoing IMRT and chemotherapy, the local failure location is mainly located in the pulmonary, and further treatment of the split dose and targets requires further clinical exploration. Key words: Lung neoplasms/radiochemoradiation; Radiotherapy, intensity-modulated; Patterns of failure

Margin reduction in radiotherapy for glioblastoma through 18F-fluoroethyltyrosine PET? – A recurrence pattern analysis

Background and purpose18F-fluoroethyltyrosine (18F-FET) PET is increasingly used in radiation treatment planning for the primary treatment of glioblastoma (GBM) patients additionally to contrast-enhanced MRI. To answer the question, whether a margin reduction in the primary treatment setting could be achieved through 18F-FET PET imaging, a recurrence pattern analysis was performed. Patients and methodsGBM patients undergoing 18F-FET PET examination before primary radiochemotherapy from 05/2009 to 11/2014 were included into the recurrence pattern analysis. Biological tumour volumes were semi-automatically created and fused with MR-based gross tumour volumes (MRGTVs). The pattern of recurrence was examined for MRGTVs and for PET-MRGTVs. The minimal margin including all recurrent tumour sites was assessed by gradual expansion of the PET-MRGTVs and MRGTVs until inclusion of all contrast-enhancing areas at recurrence. Results36 GBM patients were included to the analysis. The minimal margin including all contrast enhancing tumour at recurrence was significantly smaller for the PET-MRGTVs compared to the MRGTVs (median 12.5 mm vs. 16.5 mm; p < 0.001, Wilcoxon-Test). PET-MRGTVs with 15 mm CTV margins were significantly smaller than MRGTVs with 20 mm CTV margins (median volume 255.92 vs. 258.35 cm3; p = 0.020, Wilcoxon-Test; excluding 3 cases with large non-contrast enhancing tumours). The pattern of recurrence of PET-MRGTVs with 15 mm CTV margins was comparable to MRGTVs with 20 mm CTV margins (32 vs. 30 central, 2 vs. 4 in-field, 2 vs. 2 ex-field and no marginal recurrences). ConclusionTarget volume delineation of GBM patients can be improved through 18F-FET PET imaging prior to primary radiation treatment, since vital tumour can be detected more accurately. Furthermore, the results suggest that CTV margins could be reduced through 18F-FET PET imaging prior to primary RT of GBM.

Characteristics of long-term survivors in stage III gastric cancer patients.

163 Background: Stage III gastric cancer patients had poor prognosis. This study aims to evaluate prognostic factor of stage III gastric cancer. Methods: We retrospectively studied 126 patients who were treated for stage III gastric cancer from Jan. 2007 to Dec. 2010 at Korea University Hospital and performed complete follow up for five years. Long-term survivor was defined more than five years survivor after gastrectomy. Results: Long-term survivor was 70 patients (55.6%). Tumor size, lymph node involvement, lymphatic invasion, venous invasion and neural invasion had prognostic significance on univariate analysis. But location of tumor, gross type, depth of invasion, TNM stage, combine resection, complication, histologic differentiation, type of operation and adjuvant treatment had no prognostic significance. The most common recurrence pattern was peritoneal recurrence (57.4%) according to analysis of recurrence pattern. The disease free survival according recurrence pattern was peritoneal recurrence (21.3 months), hematogenous recurrence (32.1 months), distant lymph node recurrence (12.0 months) and locoregional (12 months). The disease specific survival according recurrence pattern was peritoneal recurrence (9.2 months), hematogenous recurrence (11.3 months), distant lymph node recurrence (16.2 months) and locoregional (26.9 months). Conclusions: Lymph node involvement were the most significant prognostic factors on stage III gastric cancer after curative resection. Therefore, postoperative surveillance and adjuvant therapy were very carefully selected in stage III gastric cancer patient with extensive lymph node metastasis.