Non-local Recurrence Research Articles

Risk Factors of Distant Recurrence and Dissemination of IDH Wild-Type Glioblastoma: A Single-Center Study and Meta-Analysis.

Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) is a highly aggressive brain tumor with a high recurrence rate despite adjuvant treatment. This study aimed to evaluate the risk factors for non-local recurrence of GBM. In the present study, we analyzed 104 GBMs with a single lesion (non-multifocal or multicentric). Univariate analysis revealed that subventricular zone (SVZ) involvement was significantly associated with non-local recurrence (hazard ratio [HR]: 2.09 [1.08-4.05]). Tumors in contact with the trigone of the lateral ventricle tended to develop subependymal dissemination (p = 0.008). Ventricular opening via surgery did not increase the risk of non-local recurrence in patients with SVZ involvement (p = 0.190). A systematic review was performed to investigate the risk of non-local recurrence, and 21 studies were identified. A meta-analysis of previous studies confirmed SVZ involvement (odds ratio [OR]: 1.30 [1.01-1.67]) and O-6-methylguanine DNA methyltransferase promoter methylation (OR: 1.55 [1.09-2.20]) as significant risk factors for local recurrence. A time-dependent meta-analysis revealed a significant association between SVZ involvement and dissemination (HR: 1.69 [1.09-2.63]), while no significant association was found for distant recurrence (HR: 1.29 [0.74-2.27]). Understanding SVZ involvement and specific tumor locations associated with non-local recurrence provides critical insights for the management of GBM.

Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

α-Smooth Muscle Actin as Predictors of Early Recurrence in Early-Stage Ductal Type Breast Cancer After Mastectomy and Chemotherapy.

Breast cancer recurrence after surgery was a sign that the progress of the disease was continuing. Early detection of breast cancer patients who are at risk requires development of a marker. Alfa smooth muscle actin (α-SMA) plays a role in the local recurrence process of invasive ductal carcinoma (IDC). Currently, existing tumor markers are used to predict the prognosis of breast cancer in general, not the early stages. Therefore, it was thought that finding α-SMA expression might predict early recurrence in early-stage IDC more accurately than others. This study investigated the potential role of α-SMA expression as a predictor of early recurrence in early-stage IDC and its relationship to clinicopathological factors. The study design was cross-sectional, with data obtained from the medical records of Dr. Koesnadi, General Hospital, Bondowoso, Indonesia. Bivariate and multivariate analysis was performed to analyze data. We included 50 subjects divided into the local recurrence group (n=25) and the non-local recurrence group (n=25). We found a statistically significant correlation between the incidence of local recurrence in early-stage IDC and the high expression of α-SMA (odd ratio [OR]=23.22, 95% confidence interval [CI]=5.101-105.7, P=0.001). Clinicopathological variables and α-SMA expression did not have a significant correlation. In early-stage IDC, α-SMA expression had the potential to predict and could be an independent prognostic factor for early recurrence.

10126-ACT-10 FACTORS AFFECTING THE PATTERN OF RECURRENCE OF IDH-WILDTYPE GLIOBLASTOMA

Abstract INTRODUCTION IDH-wildtype glioblastoma is a quite poor prognosis disease with which almost all cases recur in spite of postoperative radiation and chemotherapy. Survival rates are particularly low after dissemination. METHODS We included 120 patients with IDH-wild type glioblastoma treated at our hospital from January 2015 to December 2019. Patient backgrounds, MGMT promotor methylation status, imaging findings, and recurrence patterns were analyzed. Subependymal, subarachnoid, and spinal dissemination, plus distant metastasis, were defined as non-local recurrence. RESULTS Of 105 patients with a single lesion at diagnosis, 65 had local recurrence and 15 had non-local recurrence. 36 of 65 patients had local recurrence and 12 had non-local recurrence in the second recurrence. 17 of 36 patients had local recurrence and 8 had non-local recurrence in the third recurrence. The cumulative number of non-local recurrences was 54 (45.0%). Surgical ventricular opening and tumor proximity to the ventricles were associated with non-local recurrence (p=0.006, p=0.019). The patients with tumor proximity to the ventricle had non-local recurrence at the first recurrence and those with non-proximity to the ventricle had non-local recurrence at the second or later recurrence (p=0.038). MGMT promotor methylation status and postoperative ischemia were not significantly different from non-local recurrence (p=0.122, p=0.088), but MGMT promotor unmethylation was a risk factor for early non-local recurrence, especially within 1 year (p=0.033). Frontal lobe lesions were less frequently disseminated and more frequently MGMT promotor methylated (p=0.032, p=0.024). Parietal lobe lesions had more MGMT promotor methylation (p=0.006), and temporal lobe lesions had more dissemination (p=0.023). Distant metastasis commonly occurred from the frontal lobe to the ipsilateral or contralateral, and the frontal lobe was frequently associated. CONCLUSION IDH-wildtype glioblastoma is characterized by repeated local recurrence and cumulative non-local recurrence. The pattern of recurrence differs depending on the tumor localization, especially adjacent to ventricle, and MGMT promotor methylation status.

Longitudinal Radiomics-Based Prediction of Local Recurrence after Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Computed tomography (CT)-based radiomic analysis is an emerging tool that can help predict recurrence after radiation in non-small cell lung cancer (NSCLC). Most studies have focused on using radiomic features obtained from pre-treatment CT scans but not on post-treatment CTs. Our goal was to determine if radiomic features derived from post-treatment CTs perform better than those from pre-treatment CTs in predicting local recurrence after stereotactic body radiation therapy (SBRT) in patients with early-stage NSCLC. Patients with T1/T2 N0 early-stage NSCLC were retrospectively reviewed. Criteria for selection included patients with biopsy-proven NSCLC, non-ground glass solid lesions, 4-5 fraction SBRT treatments, and non-contrast thin-slice CTs available at pre-treatment baseline and at 3 and 6 months post-SBRT. Clinical and tumor characteristics were compared using Chi-square and Student's t-tests. CT image pre-processing was performed and 107 radiomic features were extracted using 3D Slicer and open-source software. Univariate analysis for local recurrence was determined by Cox regression with death as a competing risk. The Benjamini-Hochberg Procedure was applied to control the false discovery rate. Pearson correlation analysis was used to exclude redundant features (r > 0.8), and multivariate analysis was conducted with Random Forest on the top-performing features found on univariate logistic regression. Models were trained on a class-balanced loss to account for class imbalance. Twenty iterations of stratified 3 k-fold cross-validation were used to select the best model by the area under the receiver operating characteristic curve (AUC). We identified and analyzed 86 patient tumors, including 76 non-local recurrences and 10 local recurrences (49 males, 37 females; age, median 72, range 52-91 years). No differences in age, histology, standardized uptake values on positron emission tomography scans, gross tumor volume, and radiation dose were found between patients with and without local recurrence (all p >0.05). The median time to local recurrence was 18.9 months (range 5.5-45.6 months). At the baseline, 3-month, and 6-month timepoints, 2, 10, and 10 radiomic features predicted local recurrence on Cox regression univariate analysis, respectively (all q <0.01). On multivariate analysis of top-performing radiomic features, the 3-month timepoint performed the best with a mean (±standard deviation) AUC score of 0.82 (±0.13) compared to a mean AUC of 0.73 (±0.086) at baseline and a mean AUC of 0.74 (±0.10) at 6 months. Post-treatment radiomic features at 3 months outperformed pre-treatment radiomic features in predicting local recurrence after SBRT for NSCLC. These results suggest radiomic data from follow-up CTs may be helpful when developing radiomic models to predict local recurrence in patients with NSCLC.

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.

Is Interstitial Chemotherapy with Carmustine (BCNU) Wafers Effective against Local Recurrence of Glioblastoma? A Pharmacokinetic Study by Measurement of BCNU in the Tumor Resection Cavity.

The effectiveness of carmustine (BCNU) wafers on local recurrence of glioblastoma (GBM) remains contentious. We investigated the accumulating high-dose effects of BCNU released from the wafers on the survival of GBM patients by measuring BCNU concentration in the resection cavity of GBM over time. BCNU wafers (Gliadel®) were implanted with an Ommaya device in 15 patients, including 12 patients with GBM. BCNU concentrations in the tumor resection cavity were measured for 30 days postoperatively. The area under the curve (AUC)all was calculated from BCNU concentration curves, and the relationships between AUCall and survival, tumor phenotypes on MRI, and recurrence patterns were analyzed. The BCNU concentration was maximal 1 h postoperatively, rapidly decreased within 24 h, and remained relatively high for 7 days. GBM patients were classified into two groups: early recurrence (ER) and late or no recurrence (LN), using median progression-free survival as the cut-off. AUCall tended to be lower in the ER group than in the LN group, but the difference was not significant. MRI revealed that all patients in the ER group had highly invasive GBMs, whereas all patients in the LN group had less-invasive GBMs. A total of 9 patients experienced recurrence, with 6 local, 2 diffuse, and 1 disseminated patterns. No differences in AUCall were seen between local and non-local recurrence groups. Total BCNU concentrations did not correlate with tumor progression or survival. However, a high concentration of BCNU may have potential to provide some survival benefit for less-invasive type GBM.

High diagnostic accuracy of inguinal ultrasonography and fine-needle aspiration followed by dynamic sentinel lymph node biopsy in men with impalpable and palpable inguinal lymph nodes.

To assess the accuracy of dynamic sentinel lymph node biopsy (DSNB) after negative ultrasonography (US) guided fine-needle aspiration (FNA) for inguinal lymph node (ILN) staging. We performed a retrospective analysis of men with ≥T1G2 penile cancer and negative inguinal US-guided FNA undergoing DSNB. Men with suspicious US but negative FNA underwent US-guided ILN excision. Men with ≥T1G2 local recurrence during follow-up and non-squamous cell histologies were excluded. Descriptive analysis was performed, and sensitivity and negative predictive values (NPVs) were calculated. We included 403 men with 728 groins with negative FNA undergoing DSNB ± US-guided LN excision. At least one sentinel LN (SN) was visualised in 93% during the first and in 7% during the second lymphoscintigraphy. The median SNs visualised preoperatively was 1 SN and a median of 2 LNs were resected. ILN metastases were detected in 9% groins in men with impalpable and in 17% men with palpable LNs. Stratified by impalpable and palpable ILN, non-local recurrence despite pathologically negative DSNBs was seen in 0.5% and 0%, respectively. Limited to men with ≥24 months follow-up, non-local recurrence after negative DSNBs was seen in 0.4% and 0%, respectively. The sensitivity of DSNB was 96% and the NPV was 100%. The main limitation of this analysis is its retrospective nature with inherit biases. Inguinal US and FNA followed by DSNB can accurately stage men with both impalpable and palpable ILN, which provides logistical and surgical advantages.

High-diagnostic accuracy of inguinal ultrasonography and fine needle aspiration followed by dynamic sentinel lymph node biopsy in men with non-palpable and palpable inguinal lymph nodes.

6 Background: Penile cancer undergoes a stepwise dissemination and metastasises first to the inguinal lymph nodes (ILN). Because men can be cured in this early stage of metastatic disease, early detection and treatment is important. Methods: We performed a retrospective analysis of men with ≥T1G2 penile cancer and negative inguinal US guided FNA undergoing DSNB. Men with suspicious US but negative FNA underwent US guided ILN excision. Men with ≥T1G2 local recurrence during follow-up and non-squamous cell histologies were excluded. Descriptive analysis was performed, and sensitivity and negative predictive values (NPV) were calculated. Results: The final cohort consisted of 403 men with a median age of 65 years (IQR 55-73) and body mass index (BMI) of 28.6 kg/m² (IQR 25-33) for this analysis. This gave 728 groins with negative FNA undergoing DSNB +/- US guided lymph node excision. At least one sentinel node (SN) was visualised in 93% during the 1st and in 7% during the 2nd lymphoscintigraphy. Median SNs visualised preoperatively was 1 and a median of 2 nodes were resected. ILN metastases were detected in 9% groins with non-palpable and in 17% with palpable lymph nodes. Stratified by non-palpable and palpable ILN, non-local recurrence despite pathologically negative DSNBs was observed in 0.5% and 0%. Limited to men with at least 24 months follow-up, non-local recurrence after negative DSNBs was observed in 0.4% and 0%. The sensitivity of DSNB was 96% and NPV was 100%. The main limitation of this analysis is its retrospective nature and inherit biases. Conclusions: Our results suggest that in a high volume centre pre-operative ultrasound +/- FNA and DSNB can be used to accurately stage men with non-palpable and palpable ILN in men with ≥T1G2 penile cancer. Further, FNA in advance of surgery provides logistical and surgical advantages. In those patients with palpable disease but negative FNA, we advocate ultrasound guided excision in case of enlarged or suspicious ILN during DSNB.[Table: see text]

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy. Gitte Ørtoft; Claus Høgdall; Estrid S Hansen; Margit Dueholm. ObjectiveTo prepare for the national introduction of sentinel node staging, we evaluated the consequences of the previous national decision to introduce lymph node staging in intermediate-risk endometrial cancer patients (grade 1/2 with > 50% or grade 3 with < 50% myometrial invasion) by determining the number of patients upstaged by lymphadenectomy and whether upstaging affected the survival and recurrence patterns of non-staged patients and patients with and without lymph node metastases. Study DesignIn a national cohort study, 2005–12, 1294 stage I–IV patients who should have been offered lymphadenectomy were progressively registered. The number of patients upstaged by lymphadenectomy, 10-year survivals were evaluated by Kaplan–Meier analysis and adjusted Cox regression. ResultsThis study demonstrates that it takes time to introduce lymphadenectomy at a national level, as indicated by the increasing number of cases staged per year, from 12% in 2005 to 74% in 2012. Pelvic lymphadenectomy was performed in 43.8% (567/1294) and lymph node metastases were found in 13.6% (77/567). As 54 patients had further dissemination outside the uterine body, only 23 patients (6%) were upstaged from stage I to IIIC. Compared to lymph node-negative patients, the 77 patients with lymph node metastasis had significantly lower overall, (55% versus 68%), disease-specific (64% versus 86%), and progression-free survival (51% versus 77%), mainly due to non-local recurrences including a high number of paraaortic recurrences. In 873 final stage I intermediate-risk patients, 10-year survival and recurrence rates were not significantly lower in non-staged as compared to lymph node-negative patients (overall survival 62% versus 70%: disease-specific survival: 90% versus 90%, progression-free survival: 81% vs 83%), probably due to the low number of patients upstaged from stage I to stage IIIC. ConclusionLymph node metastases were present in 13.6% of patients with intermediate-risk who underwent pelvic lympadenectomy, and these patients had a lower 10-year survival than lymph node-negative patients. Because lymphadenectomy upstaged only 6% from stage I to stage IIIC, survival and recurrence rates were not significantly compromised in non-staged as compared to lymph node-negative intermediate-risk stage I patients. Sentinel node staging has now been implemented in Danish intermediate-risk endometrial cancer patients.

Predictive value of the new ESGO-ESTRO-ESP endometrial cancer risk classification on survival and recurrence in the Danish population

ObjectiveTo compare the performance of the new ESGO-ESTRO-ESP (European Society of Gynecological Oncology-European Society for Radiotherapy & Oncology-European Society for Pathology) 2020 risk classification system with the previous 2016 risk...

Percutaneous ablation of post-surgical solitary early recurrence of colorectal liver metastases is an effective "test-of-time" approach.

Standard treatment of early recurrence of colorectal liver metastases (CLM) after liver resection (LR) is chemotherapy followed by loco-regional therapy. We reviewed the outcome of a different strategy ("test-of-time" approach): upfront percutaneous ablation without chemotherapy. Twenty-six consecutive patients with early solitary liver-only recurrence amenable to both resection and ablation (< 30mm, distant from vessels) undergone "test-of-time" approach were analyzed. Early recurrence had a median size of 17mm and occurred after a median interval from LR of 4months. Primary efficacy rate of ablation was 100%. Five patients are alive and disease-free after a mean follow-up of 46months. Five patients had local-only recurrence; all had repeat treatment (LR = 4; Ablation = 1) without chemotherapy. Local recurrence risk was associated with incomplete ablation of 1-cm thick peritumoral margin. The remaining 16 patients had non-local recurrence, 13 early after ablation. Overall, six (23%) patients had ablation as unique treatment and 13 (50%) avoided or postponed chemotherapy (mean chemotherapy-free interval 33.5months). Ablation without chemotherapy of early liver-only recurrence is a reliable "test-of-time" approach. It minimized the invasiveness of treatment with good effectiveness and high salvageability in case of local failure, avoided worthless surgery, and saved chemotherapy for further disease progression.

Molecular Pathological Markers Correlated With the Recurrence Patterns of Glioma.

PurposeGlioma is one of the most common tumors of the central nervous system, and many patients suffer from recurrence even after standard comprehensive treatment. However, little is known about the molecular markers that predict the recurrence patterns of glioma. This study aimed to demonstrate the correlations between molecular markers and glioma recurrence patterns, which included local/nonlocal recurrence and paraventricular/nonparaventricular recurrence.MethodsImmunohistochemical techniques were used to assess the molecular markers of 88 glioma tissues following surgical resection. The recurrence patterns were divided into local recurrence, marginal recurrence, distant recurrence, multirecurrence, and subarachniod recurrence, with the last four recurrence patterns being collectively called nonlocal recurrence. According to whether the recurrence invaded ventricles, the nonlocal recurrence patterns were divided into paraventricular and nonparaventricular recurrence. Then, we compared the different recurrence patterns and their clinical characteristics, focusing on the expression of molecular markers.ResultsMore patients in the nonlocal recurrence group received combined radiotherapy and chemotherapy than patients in the local recurrence group (p=0.019). Sex, age, extent of surgery, time to recurrence, tumor location, size, and WHO grade were not different in the defined groups (P>0.05). Recurrent tumor volume and WHO grade were significantly different between the paraventricular and nonparaventricular recurrence groups (p=0.046 and 0.033). The expression of Ki-67, P53, and PCNA in the nonlocal recurrence group was significantly higher than that in the local recurrence group (p=0.015, 0.009, and 0.037), while the expression of S-100 in the nonlocal recurrence group was significantly lower than that in the local recurrence group (p=0.015). Cox regression indicated hazard ratio (HR) for high expression level of PCNA associated with non-local recurrence was 3.43 (95% CI, 1.15, 10.24), and HR for high expression level of MGMT associated with paraventricular recurrence was 2.64 (95% CI, 1.15,6.08).ConclusionsKi-67, P53, PCNA, and MGMT might be important clinical markers for nonlocal recurrence and paraventricular recurrence.

MRI-guided percutaneous thermoablation in combination with hepatic resection as parenchyma-sparing approach in patients with primary and secondary hepatic malignancies: single center long-term experience

BackgroundCombination therapy using hepatic resection (HR) and intra-operative thermal ablation is a treatment approach for patients with technically unresectable liver malignancies. The aim of this study was to investigate safety, survival and local recurrence rates for patients with technically unresectable liver tumors undergoing HR and separate percutaneous MR-guided thermoablation procedure as an alternative approach.MethodsData from all patients with primary or secondary hepatic malignancies treated at a single institution between 2004 and 2018 with combined HR and MR-guided percutaneous thermoablation was collected and retrospectively analyzed. Complications, procedure related information and patient characteristics were collected from institutional records. Overall survival and disease-free survival were estimated using the Kaplan-Meier method.ResultsA total of 31 patients (age: 62.8 ± 9.1 years; 10 female) with hepatocellular carcinoma (HCC; n = 7) or hepatic metastases (n = 24) were treated for 98 hepatic tumors. Fifty-six tumors (mean diameter 28.7 ± 23.0 mm) were resected. Forty-two tumors (15.1 ± 7.6 mm) were treated with MR-guided percutaneous ablation with a technical success rate of 100%. Local recurrence at the ablation site occurred in 7 cases (22.6%); none of these was an isolated local recurrence. Six of 17 patients (35.3%) treated for colorectal liver metastases developed local recurrence. Five patients developed recurrence at the resection site (16.1%). Non-local hepatic recurrence was observed in 18 cases (58.1%) and extrahepatic recurrence in 11 cases (35.5%) during follow-up (43.1 ± 26.4 months). Ten patients (32.3%) developed complications after HR requiring pharmacological or interventional treatment. No complication requiring therapy was observed after ablation. Median survival time was 44.0 ± 7.5 months with 1-,3-, 5-year overall survival rates of 93.5, 68.7 and 31.9%, respectively. The 1-, 3- and 5-year disease-free survival rates were 38.7, 19.4 and 9.7%, respectively.ConclusionThe combination of HR and MR-guided thermoablation is a safe and effective approach in the treatment of technically unresectable hepatic tumors and can achieve long-term survival.

On PTV definition for glioblastoma based on fiber tracking of diffusion tensor imaging data.

Radiotherapy (RT) is commonly applied for the treatment of glioblastoma multiforme (GBM). Following the planning target volume (PTV) definition procedure standardized in guidelines, a 20% risk of missing non-local recurrences is present. Purpose of this study was to evaluate whether diffusion tensor imaging (DTI)-based fiber tracking may be beneficial for PTV definition taking into account the prediction of distant recurrences. 56 GBM patients were examined with magnetic resonance imaging (MRI) including DTI performed before RT after resection of the primary tumor. Follow-up MRIs were acquired in three month intervals. For the seven patients with a distant recurrence, fiber tracking was performed with three algorithms and it was evaluated whether connections existed from the primary tumor region to the distant recurrence. It depended strongly on the used tracking algorithm and the used tracking parameters whether a connection was observed. Most of the connections were weak and thus not usable for PTV definition. Only in one of the seven patients with a recurring tumor, a clear connection was present. It seems unlikely that DTI-based fiber tracking can be beneficial for predicting distant recurrences in the planning of PTVs for glioblastoma multiforme.

Radiological Recurrence Patterns after Bevacizumab Treatment of Recurrent High-Grade Glioma: A Systematic Review and Meta-Analysis.

ObjectiveTo categorize the radiological patterns of recurrence after bevacizumab treatment and to derive the pooled proportions of patients with recurrent malignant glioma showing the different radiological patterns.Materials and MethodsA systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed to identify studies reporting radiological recurrence patterns in patients with recurrent malignant glioma after bevacizumab treatment failure until April 10, 2019. The pooled proportions according to radiological recurrence patterns (geographically local versus non-local recurrence) and predominant tumor portions (enhancing tumor versus non-enhancing tumor) after bevacizumab treatment were calculated. Subgroup and meta-regression analyses were also performed.ResultsThe systematic review and meta-analysis included 17 articles. The pooled proportions were 38.3% (95% confidence interval [CI], 30.6–46.1%) for a geographical radiologic pattern of non-local recurrence and 34.2% (95% CI, 27.3–41.5%) for a non-enhancing tumor-predominant recurrence pattern. In the subgroup analysis, the pooled proportion of non-local recurrence in the patients treated with bevacizumab only was slightly higher than that in patients treated with the combination with cytotoxic chemotherapy (34.9% [95% CI, 22.8–49.4%] versus 22.5% [95% CI, 9.5–44.6%]).ConclusionA substantial proportion of high-grade glioma patients show non-local or non-enhancing radiologic patterns of recurrence after bevacizumab treatment, which may provide insight into surrogate endpoints for treatment failure in clinical trials of recurrent high-grade glioma.

Location of recurrences in high-risk stage Iendometrial cancer patients not given postoperative radiotherapy: A Danish gynecological cancer group study.

To study recurrence rates in Danish high-risk stage I endometrial cancers not given radiotherapy in accordance with the decision of the Danish Gynecological Cancer Group. This prospective national cohort study includes all 4707 endometrial carcinomas diagnosed from 2005 to 2012. Of these, 623 patients had grade 3 endometroid adenocarcinoma with >50% myometrial invasion or serous/clear/undifferentiated carcinoma (with any depth of invasion). In 305 patients with high-risk stage I on final pathology, 14.1% received adjuvant external beam radiotherapy and 9.6% adjuvant chemotherapy. No patients received brachytherapy. 5-year Kaplan-Meier survival estimates and actuarial recurrence rates were calculated, and adjusted Cox regression analysis used for comparison. Recurrence rates were compared with historical Danish population data (DEMCA 98-99). For non-irradiated patients, 5-year overall survival, cancer-specific survival, and progression-free survival rates in high-risk stage I patients were 65%, 78%, and 73%, respectively. For non-irradiated patients, isolated local recurrences were uncommon (vaginal 3.1%, pelvic 0.4%). Death was mainly due to a high occurrence of non-local recurrences, with 8.8% experiencing a first recurrence in the abdominal cavity (outside the field where radiation traditionally have been given) and 13.0% a distant metastasis outside the abdominal cavity. Grade 3 tumors with >50% myometrial invasion seem to be characterized by a different pattern of recurrences, with significantly more isolated vaginal recurrences (7.9% vs 2.2%) and fewer total number of abdominal recurrences (7.9% vs 15.3%) as compared with unfavorable tumor types. Isolated vaginal and pelvic recurrences were rare (3-5%) in patients with a final pathologic diagnosis of high-risk stage I endometrial cancer even after the Danish Gynecological Cancer Group decided to omit all types of postoperative radiotherapy and introduce lymph node staging.

Association of pre-treatment radiomic features with lung cancer recurrence following stereotactic body radiation therapy

The purpose of this work was to investigate the potential relationship between radiomic features extracted from pre-treatment x-ray CT images and clinical outcomes following stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC).Seventy patients who received SBRT for stage-1 NSCLC were retrospectively identified. The tumor was contoured on pre-treatment free-breathing CT images, from which 43 quantitative radiomic features were extracted to collectively capture tumor morphology, intensity, fine-texture, and coarse-texture. Treatment failure was defined based on cancer recurrence, local cancer recurrence, and non-local cancer recurrence following SBRT. The univariate association between each radiomic feature and each clinical endpoint was analyzed using Welch’s t-test, and p-values were corrected for multiple hypothesis testing. Multivariate associations were based on regularized logistic regression with a singular value decomposition to reduce the dimensionality of the radiomics data.Two features demonstrated a statistically significant association with local failure: Homogeneity2 (p = 0.022) and Long-Run-High-Gray-Level-Emphasis (p = 0.048). These results indicate that relatively dense tumors with a homogenous coarse texture might be linked to higher rates of local recurrence. Multivariable logistic regression models produced maximum values of , and , for the recurrence, local recurrence, and non-local recurrence endpoints, respectively.The CT-based radiomic features used in this study may be more associated with local failure than non-local failure following SBRT for stage I NSCLC. This finding is supported by both univariate and multivariate analyses.

Risk Factors and Predictive Value of Local Recurrence in Chinese Upper Tract Urothelial Carcinoma Patients: Implication for Postoperative Adjuvant Radiation Therapy

Lymph node dissection (LND) for UTUC at the time of radical nephroureterectomy (RNU) is not routine. Patients experienced local relapse rate after surgery, this ratio can reach up to 30% in advanced stage. There is little research about the risk factors of local recurrence in UTUC patients after surgery, especially in the Chinese population. This study aim to evaluate the influence of factors and the predictive value of local recurrence in patents with upper tract urothelial carcinoma (UTUC) after nephroureterectomy and found implications for postoperative adjuvant radiotherapy. We retrospectively analyzed the clinical and pathological data of the patients with upper tract urothelial carcinoma (UTUC), who underwent nephroureterectomy between 2010 and 2016 in our center. Patients with postadjuvant radiation therapy were not enrolled in our study. We retrospectively analyzed the clinical data 330 patients after radical nephroureterectomy. With a median follow-up of 47 m (range: 4-110 months), local recurrence occurred in 73 patients (22.1%). The median interval of local recurrence was 39 months (range: 1-80 months). The probability of local recurrence-free survival at 12, 36, and 60 m was 96.2%, 90.9%, and 86.8%, respectively. Univariate and multivariate logistic regression analysis was used to address the prediction for local recurrence. In univariate analyses, statistically significant factors influencing the local recurrence were tumor multifocality, T stage, G grade, tumor location, LVI, and positive margin. In multivariate analysis tumor multifocality, T stage, G grade were significant risk factors influencing the local recurrence (P < 0.001). Local recurrence rate in T1-4 were 9.0%, 17.2%, 43%, and 37.5%. No patients experienced local recurrence in G1 grade, while 39.4% patients in G3 grade had local recurrence. Local recurrence rate was much higher in patients with multifocality (39.3% vs 18.6%, P < 0.001). Between the local recurrence group and non-local recurrence group there were statistically significant differences in 5-year metastasis recurrence-free survival (51.2% vs 93.9%, p < 0.01)and 5-year overall survival (47.1% vs 78.2%, p < 0.01). There were no significant differences in 5-year bladder recurrence survival between the two groups (66.5% vs 68.5%, P = 0.321). Local recurrence after RNU is a common event in patients with UTUC especially in T3 and T4 group. Patients with high Grade and multifocality were at high risk of recurrence. Patients with local recurrence tended to develop a metastasis recurrence and have a poor OS. This study implies some patients with high-risk local recurrence may benefit from postoperative adjuvant radiation therapy.

Does the Site of the Primary Affect Outcomes When Ablating Colorectal Liver Metastases with Radiofrequency Ablation?

To determine whether primary tumor side was a predictor of radiofrequency ablation (RFA) outcome in colorectal liver metastases (CRLM). The institutional review board approved this retrospective study. Written informed consent was obtained from all patients. From January 2007 to December 2013, 102 patients underwent RFA of metachronous CRLM were enrolled in this study with propensity score matching method. Recurrence rate (RR) and overall survival (OS) were analyzed between two patients cohorts with primary left-side colorectal cancer (LSCRC) or primary right-side colon cancer (RSCC). The total RR was 59.8% in all patients. Patients in LSCRC cohort had lower RR and non-local recurrence (NLR) rate than those in RSCC patients' cohort (49.0 vs 70.6%, p = 0.026 and 21.6 vs 41.2%, p = 0.033). Five-year OS was 14 and 30% for RSCC and LSCRC, respectively. There was a significant difference between two cohorts in median OS (29.4 vs 40.3months for RSCC and LSCRC, respectively, p = 0.042). Univariate analysis showed that primary tumor side, the number of liver metastases, tumor size, carcinoembryonic antigen level, differentiation, TNM stage, active chemotherapy and RFA boundary were significant in predicting OS. When these variables were subsequently entered in a multivariate model, RSCC (p < 0.001; hazard ratio [HR], 6.2) and tumor size (> 3cm) (p = 0.006; HR, 3.9) were significant. LSCRC and tumor size (≤ 3cm) are independent predictors of RFA in CRLM and yield the better oncologic outcomes.