Differences In Failure Patterns Research Articles

Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas

BackgroundAlliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered. MethodsSBRT (6.6 Gy x 5) was intended, although hypofractionated RT (5 Gy x 5) (HIGRT) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, 3) based on adequacy. A score of 1 indicated no deviation, a 2 indicated minor deviation, and a 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score. ResultsForty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic, 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets, while 4 were approved for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT, and 7 (17.9%) with HIGRT. Five cases (13%) required revision prior to treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2 and 11 cases (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded. ConclusionDespite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. While clinical outcomes did not appear to be impacted, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.

The effect of deep learning-based lesion segmentation on failure load calculations of metastatic femurs using finite element analysis

Bone ranks as the third most frequent tissue affected by cancer metastases, following the lung and liver. Bone metastases are often painful and may result in pathological fracture, which is a major cause of morbidity and mortality in cancer patients. To quantify fracture risk, finite element (FE) analysis has shown to be a promising tool, but metastatic lesions are typically not specifically segmented and therefore their mechanical properties may not be represented adequately. Deep learning methods potentially provide the opportunity to automatically segment these lesions and change the mechanical properties more adequately. In this study, our primary focus was to gain insight into the performance of an automatic segmentation algorithm for femoral metastatic lesions using deep learning methods and the subsequent effects on FE outcomes. The aims were to determine the similarity between manual segmentation and automatic segmentation; the differences in predicted failure load between FE models with automatically segmented osteolytic and mixed lesions and the models with CT-based lesion values (the gold standard); and the effect on the BOne Strength (BOS) score (failure load adjusted for body weight) and subsequent fracture risk assessments.From two patient cohorts, a total number of 50 femurs with osteolytic and mixed metastatic lesions were included in this study. The femurs were segmented from CT images and transferred into FE meshes. The material behavior was implemented as non-linear isotropic. These FE models were considered as gold standard (Finite Element no Segmented Lesion: FE-no-SL), whereby the local calcium equivalent density of both femur and metastatic lesion was extracted from CT-values. Lesions in the femur were manually segmented by two biomechanical experts after which final lesion segmentation for each femur was obtained based on consensus of opinions between two observers. Subsequently, a self-configuring variant of the popular deep learning model U-Net known as nnU-Net was used to automatically segment metastatic lesions within the femur. For these models with segmented lesions (Finite Element with Segmented Lesion: FE-with-SL), the calcium equivalent density within the metastatic lesions was set to zero after being segmented by the neural network, simulating absence of load-bearing capacity of these lesions. The models (either with or without automatically segmented lesions) were loaded incrementally in axial direction until failure was simulated. Dice coefficient was used to evaluate the similarity of the manual and automatic segmentation. Mean calcium equivalent density values within the automatically segmented lesions were calculated. Failure loads and patterns were determined. Furthermore, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for both groups by comparing the predictions to the occurrence or absence of actual fracture within the patient cohorts.The automatic segmentation algorithm performed in a none-robust manner. Dice coefficients describing the similarity between consented manual and automatic segmentations were relatively low (mean 0.45 ± standard deviation 0.33, median 0.54). Failure load difference between the FE-no-SL and FE-with-SL groups varied from 0 % to 48 % (mean 6.6 %). Correlation analysis of failure loads between the two groups showed a strong relationship (R2 > 0.9). From the 50 cases, four cases showed clear deviations for which models with automatic lesion segmentation (FE-with-SL) showed considerably lower failure loads. In the whole database including osteolytic and mixed lesions, sensitivity and NPV remained the same, but specificity and PPV decreased from 94 % to 83 %, and from 78 % to 54 % respectively from FE-no-SL to FE-with-SL.This study indicates that the nnU-Net yielded none-robust outcomes in femoral lesion segmentation and that other segmentation algorithms should be considered. However, the difference in failure pattern and failure load between FE models with automatically segmented osteolytic and mixed lesions were relatively small in most cases with a few exceptions. On the other hand, the accuracy of fracture risk assessment using the BOS score was lower compared to the FE-no-SL. In conclusion, this study showed that automatic lesion segmentation is a none-solved issue and therefore, quantifying lesion characteristics and the subsequent effect on the fracture risk using deep learning will remain challenging.

In Vitro Evaluation of Lithium Disilicate Endocrowns and Post and Core Crowns-A Systematic Review.

The aim of this systematic review was to summarize the results of the studies that have compared the physical and mechanical properties of lithium disilicate (LDS) endocrowns constructed for posterior teeth to those retained by post-and-core retention systems. The review was conducted following the PRISMA guidelines. The electronic search process was conducted on PubMed-Medline, Scopus, Embase and ISI Web of Knowledge (WoS) from the earliest available date till 31 January 2023. Additionally, the studies were assessed for their overall quality and risk of bias using the Quality Assessment Tool For In Vitro Studies (the QUIN). The initial search resulted in 291 articles, out of which, only 10 studies met the eligibility criteria. In all studies LDS endocrowns were compared with various kinds of endodontic posts and crowns made from other materials. There were no definite pattern or trends observed in the fracture strengths of tested specimens. There was no predilection observed in failure patters among the experimental specimens. No predilection was observed in the fracture strengths of LDS endocrowns when compared to post-and-core crowns. Furthermore, no differences in failure patterns could be observed when both types of restorations were compared. The authors propose standardized testing of endocrowns against post-and-core crowns in future studies. In conclusion, long-term clinical trials are advocated to compare the survival, failure and complication rates of LDS endocrowns and post-and-core restorations.

WNT-pathway medulloblastoma: what constitutes low-risk and how low can one go?

Novel biological insights have established that medulloblastoma is a heterogenous disease comprising four broad molecular subgroups - WNT, SHH, Group 3, and Group 4 respectively, resulting in the incorporation of molecular/genetic information in 5th edition of WHO classification and contemporary risk-stratification. Concerns regarding therapy-related late toxicity in long-term survivors have led to systematic attempts at treatment de-intensification in good-risk medulloblastoma. Given the excellent survival (>90%) of WNT-pathway medulloblastoma, prospective clinical trials have focused on optimization of therapy to balance survival versus quality of survival. The currently accepted definition of low-risk WNT-pathway medulloblastoma includes children <16 years of age with residual tumour <1.5 cm2 and no evidence of metastases. This systematically excludes adolescents and young adults who have been perceived to have worse outcomes. We have previously reported long-term survival of our adolescent and young adult cohort that were largely comparable to childhood medulloblastoma. We now report on molecularly characterized WNT-subgroup patients treated between 2004-2020 with risk-stratified multi-modality therapy to identify differences between childhood (<15 years) versus adolescent and young adults (>15 years). Despite modest differences in disease status at presentation and treatment modality, there were no significant differences in patterns of failure or survival between childhood versus adolescent and young adult WNT-pathway medulloblastoma. Two de-intensification trials in low-risk WNT-pathway medulloblastoma - first testing omission of upfront craniospinal irradiation and second a primary chemotherapy approach after surgery - had to be terminated prematurely due to unacceptably high relapse rates suggesting that craniospinal irradiation remains an integral component of treatment. The presence of TP53 mutations and OTX2 gains have recently been reported as independent negative prognostic factors in a multi-institutional cohort of WNT-pathway medulloblastoma raising questions on eligibility of such patients for de-escalation trials. The definition of low-risk WNT-pathway medulloblastoma may need to be refined in light of recent clinical data and newer biological information.

Vasculitis, CA19-9, and Perineural Invasion Differentially Predict Response and Surgical Outcome in Pancreatic Ductal Adenocarcinoma

Curative intent treatment of pancreatic adenocarcinoma (PDAC) relies on surgical resection. Modern treatment protocols focus on optimizing neoadjuvant therapy to increase resectability and improve oncologic outcomes. To elucidate differences in outcomes, we investigated the relationship between neoadjuvant chemotherapy (NAC), either with or without stereotactic body radiation therapy (SBRT), and vascular inflammation, surgical outcomes, and the resultant transcriptomic changes. Clinical data were collected from patients with borderline resectable PDAC (clinical T3-T4N0-1) who underwent NAC or NAC-SBRT followed by curative intent resection between 2014 and 2019. Vascular structures on surgical specimens were histologically evaluated for vasculitis. RNA sequencing was used to evaluate differential gene expression and to generate enrichment maps. Multivariate analysis was used to analyze the relationship between patient characteristics and oncological outcome. In total, 46 patients met inclusion criteria (n=12 NAC, n=34 NAC-SBRT) with a median follow-up of 20.1 months. All patients underwent curative resection, with 91.3% achieving R0. There was no significant difference in patterns of failure, overall survival, or progression-free survival between NAC and NAC-SBRT groups. Patients with vasculitis had a lower median overall survival compared with those without (14.5 vs 28.3 months; hazard ratio, 12.96; 95% confidence interval, 3.55-47.28; P < .001). There was no significant correlation between inflammation and surgical complications or pathologic response. Neoadjuvant therapy did not have a significant effect on development of vasculitis (odds radio, 1.64 for NAC-SBRT; 95% confidence interval, 0.40-8.43; P=.52). Predictors of poor survival included perineural invasion and high baseline carbohydrate antigen 19-9 (CA19-9) (>191 U/mL). Patients with robust CA19-9 (>20% decrease) responses to neoadjuvant therapy had enrichment in immune response, chemotaxis, and cytotoxic T-cell and natural killer-cell proliferation. Vasculitis predicts for poor survival outcomes in patients with PDAC; NAC-SBRT did not increase the rate of vasculitis compared with NAC. Perineural invasion and CA19-9 remain strong prognosticators. Understanding and optimizing immune interactions remain a crucial hurdle in achieving response in pancreatic cancer.

Difference in failure patterns after stereotactic body radiotherapy for lung cancer according to clinical Tstage based on 4D computed tomography.

Stereotactic body radiotherapy (SBRT) is atreatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical Tstage. Atotal of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. Median follow-up time was 27.5months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8months, respectively. The 3‑year PFS and OS rates were 50.7% and 60.3%, respectively. Asignificant difference was observed in PFS according to the clinical Tstage (p = 0.001). No significant differences were observed in OS according to the clinical Tstage (p = 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (p = 0.010). Clinical Tstage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to Tstage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.

Clinical Effectiveness of an Adaptive Treatment Planning Algorithm for Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Node-Positive Breast Cancer Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy

Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node-positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns. Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post). Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post). An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints.

Differences in failure patterns according to the EGFR mutation status after proton beam therapy for early stage non-small cell lung cancer

We analyzed 135 patients (including 27 EGFR-mutant and 29 EGFR-wild) with T1-3N0M0 non-squamous NSCLC treated by PBT. Considering the 3-year cumulative incidence, the EGFR-mutant group showed a significantly lower infield failure rate (9% vs 27%, p = 0.02) and higher out-of-field failure rate (67% vs 40%, p = 0.02) than the EGFR-wild group.

Difference in failure patterns of pT3-4N0-3M0 esophageal cancer treated by surgery vs surgery plus radiotherapy.

BACKGROUNDThere has been no study comparing the difference in the failure patterns between patients with or without postoperative radiotherapy (PORT) after esophagectomy for pT3-4N0-3M0 esophageal squamous cell carcinoma (ESCC).AIMTo investigate the difference in the failure patterns of stage pT3-4N0-3M0 ESCC patients with or without PORT.METHODSPatients with stage pT3-4N0-3M0 ESCC, who underwent surgery with or without PORT, were enrolled in this study. The primary endpoint was to investigate the difference in the failure patterns between patients with or without PORT after esophagectomy. The secondary endpoint was to estimate whether patients with stage pT3-4 ESCC could achieve a disease-free survival (DFS) advantage after receiving adjuvant PORT. Statistical analyses were performed by the Kaplan-Meier method, Cox regression model, and Chi-squared test or Fisher’s exact test.RESULTSIn total, 230 patients with stage pT3-4N0-3M0 ESCC were included in this study. Fifty-six patients who received PORT were screened from a prospective cohort (S + R arm). And 174 patients involving surgery alone were retrospectively selected from July 2006 to October 2014 (S arm). There were no significant differences in the clinical or pathological characteristics of patients between the two arms, except for tumor location (P = 0.031). The failure patterns between the two arms were significantly different (P < 0.001). Patients in the S arm had a significantly higher proportion of locoregional recurrence and a lower proportion of distant metastasis than those in the S + R arm (92.0% vs 35.7%, P < 0.001 and 19.0% vs 75.0%, P < 0.001, respectively). The difference in the median DFS between the two arms was statistically significant (12.7 vs 8 mo, P = 0.048). Univariate analysis and multivariate analysis both demonstrated that the number of lymph node metastases ≥ 3 (HR = 0.572, 95%CI: 0.430-0.762, P < 0.001) was an independent poor prognostic factor for DFS in patients with stage pT3-4N0-3M0 ESCC.CONCLUSIONPORT could improve DFS and local control of patients with stage pT3-4N0-3M0 ESCC. However, further studies need to be conducted to control hematogenous metastasis after PORT.

Abstract P4-10-18: Patterns of failure in a predominately black, inner city cohort of triple negative breast cancer patients at a single institution

Abstract Introduction: Triple negative breast cancer (TNBC) accounts for 12-17% of breast cancer (BC) in the US, but behaves much more aggressively. It occurs more commonly in younger, black women and death within two years of diagnosis is more common in this subset of BC compared to hormone receptor positive BC. At the University of Maryland Greenebaum Comprehensive Cancer Center, we see a higher proportion of TNBC and present our comprehensive evaluation of the patterns of failure in women with TNBC treated at our urban breast center. Materials/Methods: A retrospective review of TNBC patients treated from 2005-2017 identified 198 patients with Stage I (33%), Stage II (47%), Stage III (16%) and Stage IV (4%) TNBC. The patients were all female, median age of 54 years (range 22-86 years), 64% black, 40% married, 7% BRCA mutated, and 3% HIV positive. Tumor characteristics revealed 93% infiltrating ductal carcinoma, 68% grade 3, and 18% with lymphovascular space invasion. Self-palpation of the lesion occurred in 76% of women, and the lesion was in the upper outer quadrant 62% of the time. Thirty percent of pts had neoadjuvant and 67% adjuvant chemotherapy. Ninety-eight percent of pts underwent surgical resection, 55% had lumpectomy and 61% sentinel lymph node biopsy. Adjuvant radiation was given in 56% of patients with a median dose of 60 Gy (range 16-70 Gy). Chi-square testing was used to compare variables, while logistic regression with Kaplan-Meier estimate was used to calculate overall survival (OS) and freedom from recurrence (FFR). Results: With a median follow up of 45 months, 33 (17%) documented failures occurred. At time of first documented failure, 30% were local (L), 6% regional (R), 22% distant (D), 6% combination of L/R, 12% combination of L/R/D, 9% L/D, and 15% R/D, with a total combined failure pattern in 42% of pts. There was no significant difference in failure patterns between white and black pts (p=0.50, Table 1). The 2 and 5 year OS was 88% and 80%, respectively. Median survival was not reached in our cohort. The 2 and 5-year FFR was 90% and 84%, respectively with a median time to any failure of 16 months after initiation of therapy and median OS of 29 months for these pts. Conclusion: Our work shows that with modern BC therapies treatment outcomes for pts with TNBC are improved and 84% are free of disease at 5 yrs after the initial diagnosis. The patterns of failure in TNBC are complex, did not vary by race, and showed the largest proportion of our pts (58%) failing in distant and locoregional sites simultaneously, while an additional 30% of pts fail locally only. These failure patterns did not differ significantly based on race. Future efforts will identify pts most at risk for treatment failure for consideration of treatment intensification, as salvage options are limited when treatment failure occurs. Comparison of Failure Patterns Between White and Black PatientsFailure PatternWhite (n,%)Black (n,%)p-valueLocal only2 (22.5)8 (33) Regional only1 (11)1 (4) Distant only2 (22.5)5 (21)p=0.496Local and Regional0 (0)2 (8) Local and Distant0 (0)3 (13) Regional and Distant3 (33)2 (8) Local, Regional and Distant1 (11)3 (13) Citation Format: Rice SR, Cherng H-R, Hamza M, Murali S, Rosenblatt P, Bellavance E, Cheston S, Amin N, Nichols EM. Patterns of failure in a predominately black, inner city cohort of triple negative breast cancer patients at a single institution [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-18.

Shear test on hard coated flip-chip bumps to measure back end of the line stack reliability

Introduction of ultra-low κ (ULK) material into advanced back end of line (BEOL) stacks has improved the electrical performance of the flip-chip microelectronic packages. However, the integration of the brittle and porous ULK materials presents several mechanical reliability challenges due to chip-package interaction effects. One of the primary failure modes in a organic flip-chip microelectronic package is delamination of interlayer dielectric (ILD) layers. Thermo-mechanical stresses that arise at the end of flip-chip assembly process can be high enough to cause fracture of the ILD layers in the vicinity of a solder bump. It has been observed from experiments that two bumps subjected to apparently same amount of thermo-mechanical stresses and same process history can exhibit difference in failure pattern. Current numerical models nor micro- scale interfacial fracture characterization experiments such as double cantilever beam (DCB) or four-point bend (FPB) tests are not capable of predicting such a failure. Such a behavior is possible only if the adhesion strength of the ILD layers are not constant but varies spatially from bump to bump. The difference in adhesion strength between adjacent bumps can be attributed to the difference in trace pattern layout or via distribution. In order to understand the failure at the bump level that is sensitive to capture differences in local trace patterns, microscale test techniques need to be developed.The focus of this work is to demonstrate a new reliable microscale test technique performed using nano-indenter to measure the mechanical reliability of BEOL stacks. A high-load spherical head is used to apply a known displacement on a solder bump coated with a ceramic. The force initial increases and suddenly drops indicating failure. Cross-sections of the tested bumps clearly indicate crack propagating through the BEOL stack while the coated bump remains intact. Since the forces subjected on the bump during the test is similar to the forces subjected on the bump during flip-chip assembly, the critical force can be used as a measure of fracture strength of the BEOL stack. The results from the test indicate that the critical force varies from bump to bump and the results are repeatable. Furthermore, finite-element model of the test is developed. The failure of the ILD layers is simulated using cohesive zone (CZ) elements and the mixed-mode traction-separation parameters required to characterize the CZ elements are extracted from macro-scale test techniques like DCB and FPB tests. The force-displacement (P-Δ) plot from the model mimics the experiment and predicts the average value of the critical force observed in experiment.

Prognostic Impact of Elective Supraclavicular Nodal Irradiation for Patients with N1 Breast Cancer after Lumpectomy and Anthracycline Plus Taxane-Based Chemotherapy (KROG 1418): A Multicenter Case-Controlled Study.

PurposeThis study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy.Materials and MethodsWe performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups.ResultsA total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI.ConclusionWe did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.

Outcome analysis in patients with uterine sarcoma.

PurposeTo analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery.Materials and MethodsWe retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months).ResultsThe 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure.ConclusionThe most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.

Comparison of Clinicopathological Features and Treatment Results between Invasive Lobular Carcinoma and Ductal Carcinoma of the Breast.

PurposeThe purpose of this study was to assess the incidence of invasive lobular carcinoma (ILC) and to compare the clinicopathological features and treatment results after breast conserving surgery (BCS) followed by radiotherapy between ILC and invasive ductal carcinoma (IDC).MethodsA total of 1,071 patients who underwent BCS followed by radiotherapy were included in the study. Medical records and pathological reports were retrospectively reviewed.ResultsThe incidence of ILC was 5.2% (n=56). Bilateral breast cancer, lower nuclear grade, and hormone receptor-positive breast cancer were more frequent in patients with ILC than in those with IDC. There were no cases of lymphovascular invasion or the basal-like subtype in patients with ILC. There were no statistically significant differences in patterns of failure or treatment outcomes between patients with ILC and those with IDC. The development of metachronous contralateral breast cancer was more frequent in patients with IDC (n=27). Only one patient with ILC developed contralateral breast cancer, with a case of ductal carcinoma in situ.ConclusionThe incidence of ILC was slightly higher in our study than in previous Korean studies, but was lower than the incidences reported in Western studies. The differences we observed in clinico pathological features between ILC and IDC were similar to those described elsewhere in the literature. Although there were no statistically significant differences, there was a trend toward better disease-specific survival and disease-free survival rates in patients with ILC than in those with IDC.

Patterns of Failure in Squamous Cell Carcinoma of the Anal Canal: A Comparison Between Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy

Patterns of Failure in Squamous Cell Carcinoma of the Anal Canal: A Comparison Between Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy

Patterns of Failure after Stereotactic Body Radiation Therapy or Lobar Resection for Clinical Stage I Non–Small-Cell Lung Cancer

The purpose of this study was to compare patterns of failure between lobar resection (lobectomy or pneumonectomy) and stereotactic body radiation therapy (SBRT) for patients with clinical stage I non-small-cell lung cancer (NSCLC). From January 2004 to January 2008, 338 patients underwent definitive treatment for pathologically confirmed clinical stage I NSCLC with lobar resection (n = 260) or SBRT (n = 78). Most surgical patients underwent lobectomy (n = 237). SBRT patients received a biologically effective dose of at least 100 Gy10. Lobar resection patients were younger, healthier, and had superior pulmonary function, whereas most of the patients in the SBRT group had T1 tumors. Final pathology upstaged 32.7% of surgery patients, and 20.0% received adjuvant chemotherapy. No SBRT patients received adjuvant chemotherapy. In an unmatched comparison, 4-year lobar local control (98.7% versus 93.6%, p = 0.015) was greater for lobar resection versus SBRT, respectively, though primary tumor (98.7% versus 95.3%, p = 0.088), regional (82.9% versus 78.1%, p = 0.912), and distant control (76.1% versus 54.0%, p = 0.152) were similar. Overall survival (OS, 63.5% versus 29.6%, p < 0.0001) was greater for lobar resection, though cause-specific survival (CSS, 81.3% versus 75.3%, p = 0.923) was similar. In a T-stage matched comparison of 152 patients, there was no significant difference in patterns of failure or CSS, whereas OS favored surgery. Lobectomy/pneumonectomy or SBRT results in comparable patterns of failure for clinical stage I NSCLC. In this retrospective comparison, OS was superior for surgery, though CSS was similar. Randomized trials are necessary to control for fundamental differences in comorbidity, which impact interpretation of both tumor control and survival.

Comparison of Clinical Outcomes for Single Focus and Multifocal Glioblastoma

We investigate the differences in failure patterns and survival between multifocal and multicentric glioblastoma (GBM) and single focus GBM in the modern treatment era of 3D conformal radiation therapy and temozolomide-based chemotherapy.

Outcome analysis of cervical adenosquamous carcinoma compared with adenocarcinoma

To compare survival between patients with cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC). Retrospective study. National Taiwan University Hospital, Taipei, Taiwan. All patients with cervical AC or ASC who received definitive treatment from January 1995 to December 2009. Medical and histopathological record review. Overall and recurrence-free survival. A total of 170 women received a histological diagnosis of AC and 42 of ASC. The median follow-up was 56.7 months. There were no significant differences in age, International Federation of Gynecology and Obstetrics (FIGO) stage, gravidity or treatment modality between women with AC and ASC. Patients with ASC had a higher percentage of poorly differentiated tumors than those with AC (33.3 vs. 15.3%, respectively; p= 0.014). Five year overall and recurrence-free survival was 66.8 and 58.9%, respectively, for women with AC and 69.5 and 61.9%, respectively, for those with ASC (p= 0.795 and p= 0.892, respectively). Survival outcomes in patients with early or advanced stage disease did not differ between the histological groups. No differences in failure patterns were found between the two groups. The FIGO stage and treatment modality were factors which affected overall and recurrence-free survival. We did not find evidence to suggest that ASC subtypes indicate worse outcome. Cervical ASC could be categorized as one subtype of AC. The FIGO stage and treatment modalities have greater influence on outcomes than histological subtype.

ACL graft failure location differs between allografts and autografts

BackgroundBetween 5 and 20% of patients undergoing ACL reconstruction fail and require revision. Animal studies have demonstrated slower incorporation of allograft tissue, which may affect the mechanism of graft failure. The purpose of this study is to determine the location of traumatic graft failure following ACL reconstruction and investigate differences in failure patterns between autografts and allografts.MethodsThe medical records of 34 consecutive patients at our center undergoing revision ACL reconstruction following a documented traumatic re-injury were reviewed. Graft utilized in the primary reconstruction, time from initial reconstruction to re-injury, activity at re-injury, time to revision reconstruction, and location of ACL graft tear were recorded.ResultsMedian patient age at primary ACL reconstruction was 18.5 years (range, 13–39 years). The primary reconstructions included 20 autografts (13 hamstrings, 6 patellar tendons, 1 iliotibial band), 12 allografts (5 patellar tendon, 5 tibialis anterior tendons, 2 achilles tendons), and 2 unknown. The median time from primary reconstruction to re-injury was 1.2 years (range, 0.4 – 17.6 years). The median time from re-injury to revision reconstruction was 10.4 weeks (range, 1 to 241 weeks). Failure location could be determined in 30 patients. In the autograft group 14 of 19 grafts failed near their femoral attachment, while in the allograft group 2 of 11 grafts failed near their femoral attachment (p < 0.02).ConclusionsWhen ACL autografts fail traumatically, they frequently fail near their femoral origin, while allograft reconstructions that fail are more likely to fail in other locations or stretch.Level of evidenceLevel III - Retrospective cohort study

The use of endodontically treated and/or fiber post-retained teeth as abutments for fixed partial dentures

The purpose of this in vitro study was to evaluate the effect of endodontic treatment with or without fiber-post restorations on the fracture strength of abutment teeth under fixed partial dentures (FPDs). Seventy extracted premolar and canine teeth were used. Groups of fiber-post-retained and root-filled teeth were endodontically treated. The teeth were embedded in an acrylic resin perpendicular to the horizontal plane to create fixed partial dentures. The following groups were created using different abutments: (1) sound (S) canine/S premolar, (2) S canine/endodontically treated (ET) premolar, (3) ET canine/S premolar, (4) ET canine/ET premolar, (5) S canine/fiber-post-restored (FPR) premolar, (6) FPR canine/S premolar, and (7) FPR canine/FPR premolar. Each tooth was prepared for a complete-coverage full-metal crown. Impressions were taken; metal frameworks were fabricated and cemented. The samples were exposed to 5,000 cycles of thermomechanical fatigue and loaded compressively until fracture (2mm/min). The data were statistically analyzed using (Kruskal-Wallis test, α = 0.05). No significant difference was found among the mean fracture strengths of the groups (p = 0.696). There were distinct differences in failure patterns. All of the fracture types were horizontal, and neither vertical nor non-restorable root fractures were recorded. Premolars seemed to be a critical abutment compared to canines when they were sound under FPDs. The percentage of cervical fractures was high in endodontically treated teeth when compared to post-retained groups. In case of post-debonding, the abutment fracture did not occur. When root-filled teeth are used as abutments for FPDs, fiber-post restorations or the creation of abutments from similar structures (ET/ET or FPR/FPR) results in improved conservation of root structure under loading when compared to the abutments from different structures (S/ET, ET/S, FPR/S, S/FPR).