Marginal Failure Research Articles

Do We Need to Dose-Escalate Fractionated Stereotactic Radiation Therapy for Resected Brain Metastases?

Fractionated stereotactic radiotherapy (FSRT) represents an attractive therapeutic option for brain metastases or intracranial resection cavities not amenable to stereotactic radiosurgery. Multiple institutions utilizing various dose-fractionation schedules have demonstrated good local control. Our purpose is to report our FSRT experience in patients with 1-3 intact or resected brain metastases. Patients treated between 2014-16 were retrospectively reviewed. Planning target volume was defined as gross lesion or resection cavity plus 2-3 mm. FSRT schedules consisted of 25 Gy in 5-fractions (BED10 = 37.5 Gy, EQD2 = 31.25 Gy) and 30 Gy in 5-fractions (BED10= 48 Gy, EQD2 = 40 Gy), typically prescribed to the 95% isodose line. One-year local control (LC), local progression-free survival (PFS), and overall survival (OS) are reported using the Kaplan-Meier method. Cox regression analysis was performed to identify factors predicting for local failure. Forty-two lesions from 32 patients, including intact (N=12) and resection cavities (N=30, 71%) were identified. Two of the cavities were treated post-subtotal resection. Twenty-three (72%) patients had one target treated with FSRT. Median age for the cohort was 69 years (IQR 60, 73.5). The majority (59.5%) of metastases originated from primary lung malignancy. Twenty patients received 25 Gy and 22 patients received 30 Gy in 5-fractions. Median PTV volume was 13.3 cc (IQR 21.6,39.7). Dosimetric evaluation revealed that most (98%) of the PTVs received 95% of the prescribed dose. At a median follow-up of 6 months, local failure occurred in 3 intact lesions and 7 resection cavities. One-year actuarial LC, local PFS, and OS were: 70.8% (95% CI 51.9-83.4), 48% (95% CI 30.5-63.5), and 61.3% (95% CI 42-75.9), respectively. There was a trend toward lower 1-year LC with 25 Gy compared to 30 Gy (65% vs 87%, p=0.076). When resection cavities were evaluated separately, 1-year local failure rate was 23.3% (N=7). Six of these were in-field failures, one was a marginal failure. All of the resection cavity failures initially underwent gross total resection followed by 25 Gy in 5-fractions. There was a trend towards inferior LC with cavities treated with 25 Gy compared to 30 Gy (59% vs 100%, p=0.06). No other clinical or dosimetric parameters including histology or PTV size predicted for local failure. The observed 1-year LC rate for intact and resected metastases was comparable to that seen in other institutional experiences. Of the resection cavities that failed, almost all were in-field recurrences despite excellent target dose coverage. Resection cavities treated with a dose of 25 Gy had a higher failure rate compared to those treated with 30 Gy. These data suggest that 25 Gy in 5-fractions may not be sufficient for long-term control of resected brain metastases and higher doses should be considered.

A Phase 1/2 Trial of 5 Fraction Stereotactic Radiosurgery With 5 mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme: Pattern of Recurrence Analysis

We sought to determine the pattern of recurrence of tumors treated with 5 fractions of stereotactic radiosurgery (SRS) with 5 mm margins delivered with concurrent and adjuvant temozolomide (TMZ) in newly diagnosed glioblastoma (GBM). Thirty adult patients with newly diagnosed supra-tentorial GBM were enrolled on an institutional review board approved protocol of 5 consecutive days of SRS in escalating doses in a 3+3 design on 4 dose levels: 25 Gy, 30 Gy, 35 Gy, and 40 Gy targeting the GTV of the resection cavity/residual tumor with a 5 mm CTV margin and 0 mm PTV margin. MRI T2 edema signal was not purposely targeted. In-field recurrences were scored if the initial site of recurrence was contained within the 95% prescription isodose line (IDL), which corresponds to 5 mm margin on the cavity/residual or if contiguous with tumors within the 95% IDL. Recurrent tumor located outside of the 95% IDL, between 5 and 20 mm from the cavity (and otherwise covered with typical 2 cm margins for IMRT), were scored as marginal. Recurrences presenting more than 20 mm away from the cavity were considered distal. From 2010 to 2016, 26 patients had progressed and were eligible for pattern of recurrence analysis, with a median follow-up of 14 months (range 2-53). Seventeen out of 26 cases (65%) showed in-field recurrence within the 95% IDL, including one patient who also presented with a distal recurrence. Six patients (23%) showed purely distal recurrences, and 3 patients developed marginal failures (12%). Eight out of the 10 patients in the highest 40 Gy dose level recurred locally. Looking at marginal failures, 2 out of the 3 cases received doses above 30 Gy, including one who received 38 Gy to the failure region. The median time to progression was 3.5 months (range 0.5-17) for infield failures, 9 months (range 5-33) for marginal failures, and 17 months (range 6-22) for distal failures. Median OS was 12 months in patients with in-field recurrence vs. 21 months for distal recurrence (median OS not reached for marginal recurrence). On univariate analysis, pattern of failure was not associated with the dose level received (P = 0.422), with the MGMT methylation status of the tumor (P = 0.820), or with the extent of resection (P = 0.1051). Four out of the 6 patients who developed radionecrosis showed a distal pattern of recurrence compared to those who did not develop radionecrosis (P = 0.0245). Despite dose escalation up to 40 Gy in 5 fractions with concurrent TMZ, the dominant pattern of failure for GBM was in-field. Tumor Control Probability analyses are ongoing to determine the 2 Gy equivalent dose delivered to the 12% of tumors that progressed between 5 and 20 mm. Radionecrosis, but not total dose or MGMT status, correlated with in-field tumor control.

A Novel Methodology for Anatomically and Biologically Determined Clinical Target Volume Margin Estimation in Pediatric High Grade Glioma

CTV margins for pHGG are derived from adult HGG neuroimaging and pathology data. We developed a novel algorithm to estimate the margin required to cover the volume at risk delineated by anatomic and metabolic imaging. This method may help clinicians to objectively define anisotropic CTV margins. Twenty-six pediatric patients with HGG experienced local tumor progression after chemoradiotherapy. Progression was central, infield, and marginal in 50%, 37.5%, and 12.5% of cases, respectively. Anatomic epicenter, RANO failure type (clinical symptoms, >25% increased in T1Gd, etc.) and steroid use at progression (33%) were recorded. Tumor volumes and surgical cavities were delineated on MRI (T1+Gd, T2, FLAIR) and methionine-PET (MET-PET) at diagnosis (DTV) and failure (FTV). The distance between DTV and FTV surfaces was measured using a novel algorithm. The net progression vector (NPV), defined as the vector length approximating 80% of vectors required to cover the FTV, was calculated. Component progression vectors (CPV) were deconstructed from NPV to their x, y, and z components to estimate anisotropy in the pattern of progression (x = medial-lateral (ML), y = anterior-posterior (AP), z = craniocaudal (CC)). Comparisons of continuous and count data across disease and treatment factors were summarized using either ANOVA or the Chi-Square test. The NPV defined by T2 FLAIR and T1+Gd was 1.9 cm and 1.8 cm, respectively. NPV measurements were not significantly different according to extent of resection. NPV margin estimates differed substantially across RANO failure type. Patients exceeding RANO measured failure thresholds had increased NPV margin estimates. CPV measured 0.9 cm, 0.8 cm, and 1.0 cm in the x, y, and z directions, respectively, suggesting moderate anisotropy for all tumor locations. Midbrain, frontal, and temporal lobe tumors exhibited anisotropic extension. Frontal and midbrain tumors exhibited reduced CC extension, while frontal-temporal lobe tumors exhibited substantial AP extension. Steroid requirements at failure selected for patients with increased FLAIR defined NPV (2.2 cm vs. 1.9 cm, P = 0.15) but not the T1+Gd defined NPV. Patients with marginal failure had mildly increased NPV relative to central/infield failures (2.4 vs. 1.8 cm, P = 0.2). The MET-PET delineated NPV showed significant agreement with NPV derived from T1+Gd and T2 FLAIR imaging. The MET-PET delineated DTV overlapped the FTV in 90% of patients. NPV may be a useful method to define CTV margins in pHGG, especially for target volumes with complex geometry. Use of steroids at the time of tumor progression, RANO failure type and tumor location impacted the NPV required to cover the FTV. CPV sampling is a useful way of understanding the anisotropy of tumor extension.

Regional Nodal Failure in Head and Neck Alveolar Rhabdomyosarcoma

To assess clinical outcomes and patterns of failure, particularly regional control, for pediatric patients treated with proton therapy for head and neck alveolar rhabdomyosarcoma (HN-ARMS). Between 2006 and 2015, 14 patients with HN-ARMS were enrolled on a prospective registry protocol and treated with proton therapy at a single institution. Eight patients (57%) presented with localized disease, and 6 (43%) presented with regional nodal metastases. One patient (7%) with regional disease also had distant metastases. Ten patients (71%) were assessed for FOX01 status, and all had PAX3-FOX01 fusion transcripts. Primary site was parameningeal for 8 patients (57%), orbital for 3 patients (21%), and other head and neck for 3 patients (21%). All patients were enrolled on either COG or EpSSG protocols and treated with chemotherapy per protocol. All patients were treated with proton therapy to the primary site and involved nodal disease to median dose of 50.4 Gy(RBE) (range 39.6 – 50.4 Gy[RBE]). Elective nodal irradiation (ENI) was not used for patients without evidence of nodal disease (clinically or radiographically) at time of diagnosis. Median follow-up for surviving patients was 4.3 years. Five-year overall survival for the cohort (n = 14) was 50.2%. One patient (7%) experienced local failure, while 8 patients (57%) had regional nodal failures. Of 8 patients with no nodal disease at presentation, 6 had regional nodal failures (75%). There were no local or distant failures among these 8 patients. All 6 of these nodal regional failures involved first-echelon draining lymph node stations from the primary tumor site. Of 6 patients with nodal disease at presentation, one experienced concurrent in-field local failure and out-of-field regional failure in a nodal level where only the gross disease was treated. Another patient with nodal disease at presentation developed regional marginal failure, in a nodal basin initially involved by disease without target volume coverage of the entire nodal station. Additionally, there was no effect of the timing of proton therapy initiation on treatment failure. Proton therapy provides excellent local control for HN-ARMS. However, regional nodal failures were common among patients who did not have nodal disease at presentation. These data suggest that HN-ARMS patients may benefit from ENI. For node-positive patients, we recommend coverage of the entire nodal level due to observed high risk of failure at these sites.

Patterns of failure of diffuse large B‑cell lymphoma patients after involved-site radiotherapy.

Radiotherapy (RT) in combination with chemoimmunotherapy is highly efficient in the treatment of diffuse large B‑cell lymphoma (DLBCL). This retrospective analysis evaluated the efficacy of the treatment volume and the dose concept of involved-site RT (ISRT). We identified 60 histologically confirmed stageI-IV DLBCL patients treated with multimodal cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005-2015. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate analyses were performed by log-rank test and Mann-Whitney U‑test. After initial chemoimmunotherapy (mostly R‑CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 19 (36%) patients achieved complete response (CR), 34 (64%) partial response (PR) or less. Excluded were 7 (12%) patients with progressive disease after chemoimmunotherapy. All patients underwent ISRT with adose of 40 Gy. After amedian follow-up of 44months, 79% of the patients remained disease free, while 21% presented with failure, progressive systemic disease, or death. All patients who achieved CR after chemoimmunotherapy remained in CR. Of the patients achieving PR after chemotherapy only 2 failed at the initial site within the ISRT volume. No marginal relapse was observed. Ann Arbor clinical stageI/II showed significantly improved PFS compared to stageIII/IV (93% vs 65%; p≤ 0.021). International Prognostic Index (IPI) score of 0 or 1 compared to 2-5 has been associated with significantly increased PFS (100% vs 70%; p≤ 0.031). Postchemoimmunotherapy status of CR compared to PR was associated with significantly increased PFS (100% vs 68%; p≤ 0.004) and OS (100% vs 82%; p≤ 0.026). Only 3 of 53patients developed gradeII late side effects, whereas gradeIII or IV side effects have not been observed. These data suggest that areduction of the RT treatment volume from involved-field (IF) to involved-site (IS) is sufficient because no marginal failures occurred. The concept of IS will likely reduce the risk for late sequelae of RT.

The pattern of failure and predictors of locoregional control in lateralized buccogingival cancer after postoperative radiation therapy

BackgroundTo evaluate the failure pattern and identify predictors of locoregional control in lateralized buccogingival cancer after postoperative radiotherapy (RT) at a single institution. MethodsWe retrospectively reviewed the clinical data of 150 patients with lateralized oral squamous cell carcinoma, including carcinoma of the buccal mucosa, gingiva and retromolar trigone. All patients underwent radical surgery followed by postoperative RT with or without concurrent chemotherapy. We registered planning computer tomography images with images obtained at recurrence and categorized the failure pattern as in-field, marginal, or out-field recurrence. ResultsThe median follow-up duration was 47 months (range, 2–131 months). Twenty-eight patients (19%) experienced locoregional failure, including 20 local failure, 5 regional failure and 3 with both. Among the 24 patients who had image studies at recurrence, 15 patients had in-field recurrence, 5 were marginal recurrence and 4 were out-field recurrence. Seven patients (5%) had contralateral neck failure. Four of 5 patients with marginal failure had recurrent tumors in the infratemporal fossa. In multivariate analysis, extracapsular spread and positive or close surgical margin were associated with poor locoregional control. ConclusionLocal in-field recurrence is the most common failure pattern in lateralized buccogingival cancer after postoperative RT. The infratemporal fossa is a risk area for marginal failure and should be encompassed adequately in the postoperative RT field. Extracapsular spread and positive or close margin are predictors of locoregional control for lateralized oral cancer. Patients exhibiting such adverse features require more aggressive treatment.

Prognostic Relevance of Treatment Failure Patterns in Pediatric High-Grade Glioma: Is There a Role for a Revised Failure Classification System?

We sought to investigate the pattern of treatment failure with respect to anatomic extent, radiation dose, and criteria for failure according to the Response Assessment in Neuro-Oncology (RANO). We evaluated the corresponding prognostic significance of these factors in patients with pediatric high-grade glioma (pHGG). Fifty-six patients with pHGG were enrolled in an institutional phase 1 to 2 prospective trial that included maximal safe resection and radiation therapy with concurrent and adjuvant erlotinib. The radiation therapy dose administered was 54 to 59.4Gy at 1.8Gy/d. Tumor progression was defined according to clinical symptoms and imaging features and was classified in relation to the original extent of the tumor, radiation prescription target volume coverage, and RANO criteria (RANOc). With a median follow-up period of 90months (range, 70-124months), progression occurred in 48 patients (85.7%) while 8 (14.3%) were without progression. Central failure represented 42.6% of the total cohort, while in-field, marginal, and distant failures occurred in 7.4%, 9.3%, and 22.2%, respectively. Patients with biopsy or subtotal resection had increased rates of central failure and represented 14.81% and 16.67% of the total cohort, respectively. Tumor progression was classified as local, local plus distant, or distant. Among patients with local failure as a component of failure, 5 were considered to have marginal failure. Patients with frontal, temporal, and parietal disease had the highest rates of multifocal failure. A comparison between responses defined by RANOc demonstrated varied time to death (TTD) from progression. Pediatric high-grade glioma was shown to have high rates of central failure,particularly in cases with limited resection. Patients with central failure had a trend toward more prolonged TTD from failure relative to other failure patterns. The low marginal failure rates seen in this group suggest that less conservative radiation target margins may be possible. TTD from failure varied according to RANO type, suggesting that adult RANOc require modification before being applied to pHGG.

Local Control and Toxicity of Adaptive Radiotherapy Using Weekly CT Imaging: Results from the LARTIA Trial in Stage III NSCLC

IntroductionAnatomical change of tumor during radiotherapy contributes to target missing. However, in the case of tumor shrinkage, adaptation of volume could result in an increased incidence of recurrence in the area of target reduction. This study aims to investigate the incidence of failure of the adaptive approach and, in particular, the risk for local recurrence in the area excluded after replanning. MethodsIn this prospective study, patients with locally advanced NSCLC treated with concomitant chemoradiation underwent weekly chest computed tomography simulation during treatment. In the case of tumor shrinkage, a new tumor volume was delineated and a new treatment plan outlined (replanning). Toxicity was evaluated with the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Patterns of failures were classified as in field (dimensional and/or metabolic progression within the replanning planning target volume [PTV]), marginal (recurrence in initial the PTV excluded from the replanning PTV), and out of field (recurrence outside the initial PTV). ResultsReplanning was outlined in 50 patients selected from a total of 217 patients subjected to weekly simulation computed tomography in our center from 2012 to 2014. With a median follow-up of 20.5 months, acute grade 3 or higher pulmonary and esophageal toxicity were reported in 2% and 4% of cases and late toxicity in 4% and 2%, respectively. Marginal relapse was recorded in 6% of patients, and 20% and 4% of patients experienced in-field and out-of-field local failure, respectively. ConclusionsThe reduced toxicity and the documented low rate of marginal failures make the adaptive approach a modern option for future randomized studies. The best scenario to confirm its application is probably in neoadjuvant chemoradiation trials.

Impact of Including Peritumoral Edema in Radiotherapy Target Volume on Patterns of Failure in Glioblastoma following Temozolomide-based Chemoradiotherapy

We assessed the impact of including peritumoral edema in radiotherapy volumes on recurrence patterns among glioblastoma multiforme (GBM) patients treated with standard chemoradiotherapy (CRT). We analyzed 167 patients with histologically confirmed GBM who received temozolomide (TMZ)-based CRT between May 2006 and November 2012. The study cohort was divided into edema (+) (n = 130) and edema (−) (n = 37) groups, according to whether the entire peritumoral edema was included. At a median follow-up of 20 months (range, 2–99 months), 118 patients (71%) experienced progression/recurrence (infield: 69%; marginal: 26%; outfield: 16%; CSF seeding: 12%). The median overall survival and progression-free survival were 20 months and 15 months, respectively. The marginal failure rate was significantly greater in the edema (−) group (37% vs. 22%, p = 0.050). Among 33 patients who had a favorable prognosis (total resection and MGMT-methylation), the difference in the marginal failure rates was increased (40% vs. 14%, p = 0.138). Meanwhile, treatment of edema did not significantly increase the incidence of pseudoprogression/radiation necrosis (edema (−) 49% vs. (+) 37%, p = 0.253). Inclusion of peritumoral edema in the radiotherapy volume can reduce marginal failures following TMZ-based CRT without increasing pseudoprogression/radiation necrosis.

OA24.02 Locally Advanced Non-Small Cell Lung Cancer: RadioTherapy with Adaptive Strategy (LARTIA Trial)

Anatomical change of tumor contour during radiotherapy contributes to target missing. Adaptation of tumor volume could however result in an increased incidence of recurrences in the area of target reduction. This study aims to investigate the incidence of failure of adaptive approach in evaluating the risk of local recurrence in the area excluded during replanning. In this prospective study, LA-NSCLC patients treated with concomitant chemoradiation underwent weekly chest-CT simulation during therapy. In case of tumor shrinkage, a new tumor volume (TV) was delineated and a new treatment plan outlined (replanning). Patterns of failure were classified as: in field (persistence or recurrence in TV post-replanning), marginal (recurrence in the area of initial TV excluded from the post-replanning TV) and out of field (recurrence outside of initial TV). Toxicity, OS, and PFS were reported. A total of 217 NSCLC patients were treated in our center from 2012 to 2014. In 50 cases a target volume reduction was recorded and replanning outlined. A mean initial and replanning CTV of 154.9cc and 90.7cc were reported with an average CTV shrinkage of 42% between simulation CT and replanning CT. With a median follow-up of 20.5 months, 30% of patients experienced local failure which was in field, marginal and out of filed in 20%, 6% and 4% of cases respectively. Acute G3 pulmonary and esophageal toxicity was reported in 2% and 4% of patients respectively. The possibility to reduce toxicity and the documented low rate of marginal failures makes the adaptive approach a modern option for future randomized studies. The best scenario to confirm tumor activity is its application in neoadjuvant chemoradiation trials.

Estimation of the Frank copula model for dependent competing risks in accelerated life testing

A competing risks situation where a potential critical unit failure at random time \(X_2\) in a life test may be avoided by observing a degraded failure at some random time \(X_1\) is considered. It is thus logical to expect a dependence between the event times \(X_1\) and \(X_2\). We model the joint distribution of \(X_1\) and \(X_2\) by the Frank copula because it captures the full range of dependence and it is symmetric in its dependence structure. This paper shows how expert opinion is used to estimate the assumed Frank copula when only incomplete competing risks data are observed. Estimation of the copula allows the marginal distributions to be identified from competing risks data. Our result is thus apparent in reliability where primary interest is in the estimation of marginal failure distributions and can be extended to other applications.

Gamma Knife radiosurgery for neurofibromatosis type 2-associated meningiomas: a 22-year patient series.

Neurofibromatosis type 2 (NF2) is a debilitating genetic condition with potential development of multiple meningiomas. We report our experience treating a series of NF2-associated intracranial meningiomas with Gamma Knife radiosurgery (GKRS). Between 1992 and 2013, 15 consecutive patients (age 20-54 years) with 62 intracranial meningiomas were treated with single-fraction GKRS. Fifty-five percent of tumors involved the convexity or parasagittal/falx. The median prescription dose was 16Gy (range 13-20Gy). The median tumor diameter was 2.1cm (range 0.7-4.5cm). The median radiographic and clinical follow-up periods were 103 and 111 months, respectively. The 5-year and 10-year local controls were both 96 %. The disease specific survival was 93 % at 5 years and 68 % at 10 years. Fifty-three percent of patients had multiple meningiomas and received multiple GKRS treatments (range 1-7) for new or enlarging intracranial meningiomas. 11 (73 %) patients were alive at last follow-up, with 60 (97 %) tumors controlled (smaller or unchanged in size). There were 2 in-field failures, one at 1year and the other at 3.5 years. There were no marginal failures. Major Complications after GKRS included: 1 case of radiation necrosis, 1 case of post treatment edema, and 1 case of a presumed radiation induced cavernous malformation 5 years after GKRS. GK is an effective treatment for enlarging NF2-associated meningiomas. No cases of malignant transformation or secondary malignancies were seen during the follow-up period.

Patterns of Failure in Pediatric Rhabdomyosarcoma After Proton Therapy

To report on the patterns of failure in children with rhabdomyosarcoma treated with proton therapy. Between February 2007 and November 2013, 66 children with a median age of 4.1years (range, 0.6-15.3years) diagnosed with nonmetastatic rhabdomyosarcoma were treated with proton therapy. Clinical target volume 1 was defined as the prechemotherapy tumor plus a 1-cm anatomically constrained margin. Clinical target volume 2 was defined as the postchemotherapy tumor (or tumor bed) plus a 0.5-cm anatomically constrained margin, further expanded to encompass potential pathways of spread, including soft tissue infiltrated with tumor at diagnosis. Of the 66 children, 11 developed locally progressive disease at a median of 16months (range, 14-32months), for an actuarial 2-year local control rate of 88%. Among the children who progressed, median age and tumor size at diagnosis were 6.7years (range, 0.6-16years) and 6cm (range, 2-8cm), respectively. Of the recurrences, 64% and 36% were embryonal and alveolar, respectively. Disease progression was observed in 7 (64%) parameningeal, 2 (18%) head and neck (other), and 2 (18%) bladder/prostate subsites. At diagnosis, 8 of 11 patients who developed a recurrence were Intergroup Rhabdomyosarcoma Study stage 3, and all 11 were group III. Of the relapses, 100% (11 of 11) were confirmed as in-field within the composite 95% isodose line. One of the 11 patients (9%) developed a new simultaneous regional nodal recurrence outside of the previously treated radiation field. Early data suggest that the sharp dosimetric gradient associated with proton therapy is not associated with an increased risk of marginal failure. Routine use of a 0.5- to 1-cm clinical target volume 1/2 margin with highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features.

Patterns of failure and prognostic factors for radically treated patients of oropharyngeal cancers planned by two-dimensional radiotherapy: An audit from a regional cancer center

Objectives: To review the patterns of failure and analyze various prognostic factors influencing the outcomes of radically treated patients of oropharyngeal squamous cell cancer treated at our institute with two-dimensional planning (2D). Materials and Methods: Case records of 100 oropharyngeal squamous cell cancers, which were treated radically with radiation or concurrent chemoradiation to an equivalent dose of 66 Gy in conventional fractionation, in our department between 2011 and 2013 were retrospectively analyzed for locoregional control (LRC), progression-free survival (PFS), patterns of failure, and various prognostic factors. Results: Median age of presentation was 53 years, 95% being males. Ninety-three percent had a history of tobacco use. Base of tongue was the most common site in 63% of patients followed by tonsil in 26%. All patients were of Stage III and IV. Among these patients, 27% received concurrent chemoradiation while others received radical radiation. At a median follow-up of 28 months, 57% of the patients were disease free and the LRC was 60%. Among the recurrences, 17% had local failures while 23% had nodal failures as the first site of recurrence. There were no marginal failures. On multivariate analysis, stage of the disease was the single most important prognostic factor determining the PFS and LRC. Conclusion: Stage appears to be the most important prognostic factor affecting LRC and PFS. Absence of marginal failures in our study implies adequacy of coverage with 2D treatment planning while in-field failures mandate attempts to use increased dose, chemosensitizers or nodal dissection postradical radiation.

Marginal adaptation, fracture resistance and failure patterns of two CAD /CAM overlays

Marginal adaptation, fracture resistance and failure patterns of two CAD /CAM overlays

Inclusion of Peritumoral Edema in the Delineation of Radiation Therapy Target Volume Reduces Marginal Failures in Glioblastoma Patients Undergoing Standard Temozolomide Based Chemoradiation

Inclusion of Peritumoral Edema in the Delineation of Radiation Therapy Target Volume Reduces Marginal Failures in Glioblastoma Patients Undergoing Standard Temozolomide Based Chemoradiation

Clinical outcome of image-guided adaptive radiotherapy in the treatment of lung cancer patients

ABSTRACTBackground. Adaptive strategy with daily online tumour match is a treatment option when treating locally advanced lung cancer patients with curative intended radiotherapy (RT).Material and methods. Fifty-two consecutive lung cancer patients treated with soft tissue match, adaptive RT and small planning target volumes (PTV) margins were analysed. A control group of 52 consecutive patients treated with bone match, no adaptive strategy and larger margins was included. Patients were followed with computed tomography (CT) scans every third month. CT-images showing loco-regional recurrences were identified. The recurrence gross tumour volume was delineated and registered with the original radiation treatment plan to identify site of failure. All patients were toxicity-scored using CTCAE 4.03 grading scale. Data were analysed using the Kaplan-Meier analysis.Results. The median follow-up time was 16 months (3–35). Within a year, 35% of the patients in the adaptive group (ART-group) and 53% in the control group (No-ART-group) experienced loco-regional failure, showing improved loco-regional control in the ART group (p = 0.05). One patient in the ART-group and four patients in the No-ART-group showed marginal failure. Median overall progression-free survival time for the ART-group was 10 months (95% CI 8–12), and 8 months (95% CI 6–9) for the No-ART-group. Severe pneumonitis (grade 3–5) decreased from 22% in the No-ART-group to 18% in the ART-group (non-significant, p = 0.6). No significant difference in severe dysphagia was found between the two groups.Conclusion. In the first small cohort of patients investigated, implementation of soft-tissue tumour match and adaptive strategies for locally advanced lung cancer patients increased the loco-regional control rate without increasing treatment-related toxicity.

Failures in composite restoration

In recent years, the popularity of tooth colored restorative material has led to a rapid increase in the use of resins. This critical review paper is meant to be useful contribution to the recognition & understanding of problems related to the failures of composite restoration. This review categorizes the challenges as those related to the restorative materials, the dentist and the patients. In spite of the major improvements in both physical and mechanical characteristics following factors are still of major concern, such as improper case selection, isolation, wear resistance, cavity preparation, placement of composites, curing, finishing & polishing. Major problems associated with composites failures are polymerization shrinkage & contraction stress related to polymerization shrinkage, water sorption, solubility, discoloration of restoration (staining), elution of material from restoration, marginal failures, secondary caries, and fracture of the restoration, post-operative sensitivity, and micro-leakage.

SU‐E‐E‐05: Improving Contouring Precision and Consistency for Physicians‐In‐Training with Simple Lab Experiments

Purpose:Target contouring for high‐dose treatments such as radiosurgery of brain metastases is highly critical in eliminating marginal failure and reducing complications as shown by recent clinical studies. In order to improve contouring accuracy and practice consistency for the procedure, we introduced a self‐assessed physics lab practice for the physicians‐in‐training.Methods:A set of commercially acquired high‐precision PMMA plastic spheres were randomly embedded in a Styrofoam block and then scanned with the CT/MR via the clinical procedural imaging protocol. A group of first‐year physicians‐in‐training (n=6) from either neurosurgery or radiation oncology department were asked to contour the scanned objects (diameter ranged from 0.4 cm to 3.8 cm). These user‐defined contours were then compared with the ideal contour sets of object shape for self assessments to determine the maximum areas of the observed discrepancies and method of improvements.Results:The largest discrepancies from initial practice were consistently found to be located near the extreme longitudinal portions of the target for all the residents. Discrepancy was especially prominent when contouring small objects < 1.0 cm in diameters. For example, the mean volumes rendered from the initial contour data set differed from the ideal data set by 7.7%±6.6% for the participants (p> 0.23 suggesting agreement cannot be established). However, when incorporating a secondary imaging scan such as reconstructed coronal or sagittal images in a repeat practice, the agreement was dramatically improved yielding p<0.02 in agreement with the reference data set for all the participants.Conclusion:A simple physics lab revealed a common pitfall in contouring small metastatic brain tumors for radiosurgical procedures and provided a systematic tool for physicians‐in‐training in improving their clinical contouring skills.Dr Ma is current a board member of international stereotactic radiosurgical society

Development of highly reliable static random access memory for 40-nm embedded split gate-MONOS flash memory

High quality static random access memory (SRAM) for 40-nm embedded MONOS flash memory with split gate (SG-MONOS) was developed. Marginal failure, which results in threshold voltage/drain current tailing and outliers of SRAM transistors, occurs when using a conventional SRAM structure. These phenomena can be explained by not only gate depletion but also partial depletion and percolation path formation in the MOS channel. A stacked poly-Si gate structure can suppress these phenomena and achieve high quality SRAM without any defects in the 6σ level and with high affinity to the 40-nm SG-MONOS process was developed.