Patterns Of Locoregional Failure Research Articles

Patterns of Loco-Regional Failure In HPV-Associated Oropharyngeal and Unknown Primary Cancers After Definitive Chemoradiation: Implications For Elective Nodal Coverage

Patterns of Loco-Regional Failure In HPV-Associated Oropharyngeal and Unknown Primary Cancers After Definitive Chemoradiation: Implications For Elective Nodal Coverage

Patterns of locoregional failure in locally advanced non-small cell lung cancer treated with definitive conformal radiotherapy: Results from the Gating 2006 trial

PurposeTo determine the patterns of locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy (RT). Patients and methodsOne hundred and fifty-four patients from the Gating 2006 prospective randomized trial were treated with conformal RT with or without respiratory motion management. For patients with a LRF as first event, treatment planning with simulation CT, pre-treatment 18FDG PET-CT and post-treatment images demonstrating recurrence were registered and analyzed. Measurable LRF was contoured (rGTV) and classified as in-field, marginal, or out-of-field. ResultsMedian follow-up was 27.8 months. Forty-eight patients presented with LRF. One-year and 2-year locoregional disease-free survival rates were 77% (95% CI 70–83) and 72% (95% CI 64–79) respectively. 79% of the patients with LRF as first event relapsed within the RT field (55% isolated), 30% had marginal LRF component. Isolated out-of-field failure occurred in only 3% of all patients. The regions of highest FDG-uptake on pre-treatment PET-CT were located within the recurrence in 91% of patients with in-field LRF. ConclusionIn-field failure was the most common pattern of failure. Escalated dose RT with high-dose fractions guided by PET parameters warrants further investigation.

Patterns of Locoregional Failure in Women With Early Stage Breast Cancer Treated by Whole Breast Radiation Therapy in the Lateral Isocentric Decubitus Position: Large-Scale Single Center Experience

Patterns of Locoregional Failure in Women With Early Stage Breast Cancer Treated by Whole Breast Radiation Therapy in the Lateral Isocentric Decubitus Position: Large-Scale Single Center Experience

Patterns of Locoregional Recurrence in Breast Cancer Patients After Neoadjuvant Chemotherapy and Adjuvant Radiation Therapy

Neoadjuvant chemotherapy is considered a viable option for patients with palpable breast cancer. There is limited information about patterns of locoregional recurrence (LRR) in breast cancer patients after neoadjuvant chemotherapy (NC), which has resulted in difficult identification of the rates and the predictors of LRR after NC. The main objective of this study is to determine the patterns of locoregional failure in breast cancer patients who received NC and adjuvant radiation. This is a retrospective analysis including 811women who received different chemotherapeutic agents as NC for stage I, II&III breast cancer and treated between 1997 and 2014. The patients’ median age was 49.2 (range 24.3-83.7 years). 28 patients (3.4%) were diagnosed with stage I, 479 (61.2%) with stage II, 229 (28.2%) with stage III and 58 (7.1%) with no preoperative staging. 391 patients underwent lumpectomy (48.2 %) while 417 (51.4%) underwent mastectomy and 3 didn't undergo any surgery. 196 (24.2%) showed pathological complete response pCR, 566 (69.8%) with pathological partial response (pPR), 38 (4.7%) with pathological no response/progression (pNR) while 11 (0.1%) were not assessed for pathological response. 722 (89%) patients received radiotherapy and 83 (10.2%) did not. In 6 patients (0.4%) there was no available data on their radiation treatment. Factors associated with LRR were assessed utilizing the Kaplan-Meier method and Logistic regression model. The median follow up period for all patients was 66.5 months. The rate of LRR was 5.1% at 5 years and 9% at 10 years. The overall and disease-free survival rates at five were (89.1%), (83.1%) respectively and at ten years were (80.9%) (68.7%) respectively. 184 patients (22.7%) developed distant metastasis and 52(7%) developed LRR. The median time for LRF was 1.5 years. 69% of LRF occurred in breast and or chest wall, 10% in axilla, and 15.4% in supraclavicular area and 5.6 in other sites. We found that LRR was significantly associated with the presence of lymph-vascular invasion (LVI) at the time of surgery (P=0.008). We also noticed that the rate of LRR was higher among patients who had pNR (P=0.02). Other factors as age, tumor pathology and type of surgery were not significant. These data suggest that the presence of LVI and pNR at the time of surgery after NC is associated with a significantly higher rate of LRR, and both can be considered as predictors for local failure after NC.

Patterns of locoregional failure following post-operative intensity-modulated radiotherapy to oral cavity cancer: quantitative spatial and dosimetric analysis using a deformable image registration workflow

BackgroundWe sought to identify spatial/dosimetric patterns of failure for oral cavity cancer patients receiving post-operative IMRT (PO-IMRT).MethodsTwo hundred eighty-nine OCC patients receiving PO-IMRT were retrospectively reviewed from 2000 to 2012. Diagnostic CT documenting recurrence (rCT) was co-registered with planning CT (pCT) using a validated deformable image registration software. Manually segmented recurrent gross disease (rGTV) was deformed to co-registered pCTs. Mapped rGTVs were compared dosimetrically to planned dose and spatially to planning target volumes using centroid-based approaches. Failures types were classified using combined spatial/dosimetric criteria: A (central high-dose), B (peripheral high-dose), C (central intermediate/low-dose), D (peripheral intermediate/low-dose), and E (extraneous-dose).ResultsFifty-four patients with recurrence were analyzed; 26 local recurrence, 19 regional recurrence, and 9 both local and regional recurrence. Median time to recurrence was 4 months (range 0–71). Median rGTVs volume was 3.7 cm3 (IQR 1.4–10.6). For spatial and dosimetric analysis of the patterns of failure, 30 patients (55.5%) were classified as type A (central high-dose). Non-central high dose failures were distributed as follows: 2 (3.7%) type B, 10 (18.5%) type C, 1 (1.8%) type D, and 9 (16.7%) type E. Non-IMRT failure in the matching low-neck field was seen in two patients. No failures were noted at the IMRT-supraclavicular field match-line.ConclusionsApproximately half of patients with local/regional failure had non-central high dose recurrence. Peripheral high dose misses were uncommon reflecting adequate delineation and dose delivery. Future strategies are needed to reduce types C and E failures.

Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal Field Design for Adjuvant Radiation Therapy

To identify prognostic factors and patterns of local failure in patients with cholangiocarcinoma (CCA), after surgical resection in the absence of adjuvant radiation, for optimal definition of target volumes encompassing the majority of local recurrences. A chart review was performed in patients who underwent resection for primary CCA (intrahepatic, hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence in a theoretical reasonable postoperative radiation volume. This includes the cut surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri-pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who received adjuvant radiation were excluded. A total of 189 patients underwent surgical resection for CCA, of whom 145 patients had sufficient follow-up. Median follow-up was 41.6months (95% confidence interval 35.4-48.7months). Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine-based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%) had a locoregional component. Among patients who had a recurrence, 23 (27%) had a recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis identified tumor size, any vascular invasion, presence of satellites, stage/nodal status, and receipt of chemotherapy as significant prognostic factors of overall recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx status remained statistically significant in multivariable modeling. Theareas at highest risk for locoregional recurrence after surgical resection for primary CCA are the biliary anastomosis/cut liver surface, portal lymph nodes, and retroperitoneal lymph nodes. Although these results need to be validated, adjuvant radiation should possibly cover these areas to maximize locoregional control.

Patterns of loco regional failure in women with breast cancer treated by Postmastectomy Conformal Electron Beam Radiation Therapy (PMERT): Large scale single center experience

To evaluate loco regional control and describe the patterns of loco regional failure in women with breast cancer irradiated by a previously described post-mastectomy highly conformal electron beam radiotherapy technique. We included all women irradiated by PMERT for non-metastatic breast cancer (BC) between 2007 and 2011 in our department. All cases of bilateral BC were excluded. All patients who experienced loco regional recurrence have been studied. Mapping patterns of regional recurrences was also performed and compared with the ESTRO and RTOG Guidelines of volume definition and delineation guidelines. Among the 796 women included, 10.1% were triple-negative (TN) and 18.8% were HER2-positive and 24.6% of them had received neoadjuvant chemotherapy (CT). Internal mammary chain (IMC), supraclavicular (Level IV), infraclavicular (Levels III and II) and axillary LN (Level I) were treated in 85.6%, 88.3%, 77.9% and 14.9% of cases, respectively. With a median follow-up of 64months (range: 6-102), 5-year locoregional (RFS and OS were 90% (95% CI: 88.1-92.4) and 90.9% (95% CI: 88.9-93), respectively. Twenty-three patients (2.9%) presented locoregional recurrences. Most of them presented aggressive biological features with grade III tumors in 17 patients (74%) with high mitotic index in 16 cases (70%) and triple negative tumors in 12 (52%). Lymphovascular invasion (LVI) was observed in 11 cases (48%). In 14 cases the locoregional recurrences were diagnosed at the same time as the metastatic disease whereas 4 patients presented distant metastases secondarily. Local (Chest wall) recurrences occurred in 13 cases (56%) with the coverage by the isodose of 47.5Gy (isodose 95%). Fifteen regional recurrences (lymph nodes) were observed in 13 patients. Only 3 regional recurrences occurred within irradiated volumes and 12 regional recurrences occurred outside irradiated areas. In presented series, the local recurrences were related mostly to the tumor biological aggressivity and radio resistance. Small number was caused by geographical miss. Further follow-up and careful registration of the recurrences is needed to improve their understanding.

EP-1096: Using DIR to study patterns of loco-regional failure in patients with head and neck cancer

EP-1096: Using DIR to study patterns of loco-regional failure in patients with head and neck cancer

Abstract P1-10-10: Risk factors of locoregional recurrence, locoregional failure pattern and role of postmastectomy radiotherapy for T1-2 breast cancers with 1-3 positive axillary lymph nodes

Abstract This abstract was not presented at the symposium.

Survival and Toxicities of IMRT Based on the RTOG Protocols in Patients with Nasopharyngeal Carcinoma from the Endemic Regions of China.

Background: This study evaluated the survival outcomes and toxicities of intensity-modulated radiation therapy (IMRT) based on the RTOG 0225/0615 RT protocols in patients with nasopharyngeal carcinoma (NPC) from a region of China where this tumor type is endemic.Methods: A total of 455 patients with non-metastatic, histologically-confirmed NPC were retrospectively reviewed. All patients were treated by IMRT using the RTOG 0225/0615 RT protocols; 91.1% (288/316) of patients with stage III-IVb NPC received concurrent chemotherapy +/- induction chemotherapy or adjuvant chemotherapy.Results: Estimated four-year overall survival (OS), failure free survival (FFS), local relapse free survival (LRFS), regional relapse free survival (RRFS) and distant metastasis free survival (DMFS) were 83.8%, 80.5%, 94.3%, 96.7% and 85.8%, respectively. T and N category were significant prognostic factors for OS, FFS, RRFS and DMFS; and T category, for LRFS. In-field failure was the major loco-regional failure pattern. During RT, 206 (45.3%) patients experienced acute grade 3-4 toxicities. The most common acute toxicity was mucositis; 124 (27.2%) patients experienced grade 3-4 mucositis; 46 (10.1%) experienced serious late toxicities. The most common late toxicity was MRI-detected radiation-induced temporal lobe necrosis (6.8%).Conclusions: The RTOG IMRT protocols are feasible for patients with NPC from the endemic regions of China.

Methodology for analysis and reporting patterns of failure in the Era of IMRT: head and neck cancer applications.

BackgroundThe aim of this study is to develop a methodology to standardize the analysis and reporting of the patterns of loco-regional failure after IMRT of head and neck cancer.Material and MethodsTwenty-one patients with evidence of local and/or regional failure following IMRT for head-and-neck cancer were retrospectively reviewed under approved IRB protocol. Manually delineated recurrent gross disease (rGTV) on the diagnostic CT documenting recurrence (rCT) was co-registered with the original planning CT (pCT) using both deformable (DIR) and rigid (RIR) image registration software. Subsequently, mapped rGTVs were compared relative to original planning target volumes (TVs) and dose using a centroid-based approaches. Failures were then classified into five types based on combined spatial and dosimetric criteria; A (central high dose), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose).ResultsA total of 26 recurrences were identified. Using DIR, recurrences were assigned to more central TVs compared to RIR as detected using the spatial centroid-based method (p = 0.0002). rGTVs mapped using DIR had statistically significant higher mean doses when compared to rGTVs mapped rigidly (mean dose 70 vs. 69 Gy, p = 0.03). According to the proposed classification 22 out of 26 failures were of type A (central high dose) as assessed by DIR method compared to 18 out of 26 for the RIR because of the tendencey of RIR to assign failures more peripherally.ConclusionsRIR tends to assigns failures more peripherally. DIR-based methods showed that the vast majority of failures originated in the high dose target volumes and received full prescribed doses suggesting biological rather than technology-related causes of failure. Validated DIR-based registration is recommended for accurate failure characterization and a novel typology-indicative taxonomy is recommended for failure reporting in the IMRT era.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-016-0678-7) contains supplementary material, which is available to authorized users.

Mapping of failures after radiochemotherapy in patients with non-metastatic esophageal cancer: A posteriori analysis of the dose distribution in the sites of loco-regional relapse

Background and purposeWe aimed to evaluate the patterns of loco-regional failure (LRF) after exclusive chemoradiotherapy (eCRT) for esophageal cancer with respect to planned dose and/or the incidental (unplanned) dose outside target volumes. Materials and methodsCo-image registration of CT or 18F-FDG PET-CT at the time of failure (tf) and at the time of CRT (t0) was performed in 34 patients with LRF. Dosimetric parameters with regard to local failure (LF), nodal failure (NF) and involved nodal stations (NS) were derived. ResultsTwenty-two patients (64.7%) had LF, the majority of which (95.5%) were located at the epicenter of the GTV of the primary tumor. The mean doses recalculated to the NS at tf were more likely to be lower than the planned dose delivered to the PTV at t0: Dmean=33.9±20.8Gy vs 52.2±8.5Gy (p=0.0009), D95%=27.5±21Gy vs 46.1±4.8Gy (p=0.004). Among the 12 patients with NF outside the elective nodal irradiation (ENI) volume, Dmean of NS outside the ENI was significantly lower (19.4±21.4Gy) than the Dmean of NS with failure within the ENI (45.1±6.1Gy, p=0.01). ConclusionLoco-regional failure after exclusive chemoradiotherapy for esophageal cancer may be due to an inadequately low dose.

Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and laryngeal squamous cell carcinoma: mature treatment results and patterns of locoregional failure.

PurposeTo assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.MethodsData from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities. Time-to-event endpoints were estimated using Kaplan-Meier method, and univariate and multivariate analyses were performed using Cox proportional hazards models. Recurrent gross tumor volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20–95% inside CTV; out-volume, < 20% inside CTV).ResultsFifty patients (stage III: 14, IVa: 33, IVb: 3) completed treatment and were included in the analysis (median follow-up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96% and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%, respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We identified 10 patients with LRF (8 local, 1 regional, 1 local + regional). Six out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4 RTVs were marginal to the high-dose CTVs.ConclusionThe treatment of locally advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of LRFs in relation to CTVs showed in-volume relapses to be the major mode of recurrence indicating that novel strategies to overcome radioresistance are required.

Methods for Analysis and Reporting the Patterns of Locoregional Failure in the Era of IMRT for Head and Neck Cancer: Deformable Image Registration–Based Quality Assurance Workflow

The accurate and specific reporting of the exact site of loco-regional failure after intensity modulated radiation therapy (IMRT) of head and neck cancer in addition to the dose given to this site is mandatory to identify the possible causes of failure. Our aim is to develop a workflow methodology to accurately define the area of recurrent/persistent disease relative to the original planning target volumes (TVs) and prescribed radiation doses using a validated deformable image registration (DIR) software.

Patterns of locoregional failure in stage III non-small cell lung cancer treated with definitive chemoradiation therapy

PurposeChemoradiation therapy (CRT) is the core treatment of locally advanced non-small cell lung cancer (LA-NSCLC), but potential toxicities limit radiation therapy dose. These toxicities, plus the advent of increasingly conformal radiation therapy, have prioritized target definition and the use of involved-field radiation therapy (IFRT). Published data largely focus on regional rather than local failure patterns. We report our pattern-of-failure experience treating patients with LA-NSCLC with definitive CRT, focusing on both local and regional recurrences with detailed dosimetric analyses of failure location. Methods and materialsPatients treated between December 2004-2010 were included. Imaging scans from date of failure were fused with the RT-planning CT scan, and recurrent nodes were contoured to determine if the recurrence was in a previously irradiated region, defined as involved nodal recurrence (INR) versus elective nodal recurrence (ENR). Local failures were contoured and identified as in-field, marginal, or out-of-field based on dose received. Actuarial overall survival (OS) and progression-free survival (PFS) were calculated, and the cumulative incidences of local, regional, locoregional, and distant recurrence (CILR, CIRR, CILRR, CIDR) were determined with death as a competing risk. ResultsOne hundred five patients were included with a median survival of 21.8 months. The 3-year OS and PFS were 36% and 22%, respectively. The 3 year CILRR, CILR, CIRR, CIDR were 41%, 38%, 40%, and 58%, respectively. Thirty patients failed regionally, but only 7 patients developed an ENR with no concurrent local failure or INR, and only 1 of these patients did not develop distant metastases within 1 month of recurrence. A total of 21 patients (20%) developed an ENR with or without other areas of recurrence. ConclusionsElective regional recurrences rarely occurred as the sole site of failure, despite the use of IFRT. Moreover, the pattern of local failure was entirely in-field. These data strongly support field design focusing on gross nodal and primary disease.

Pattern of loco-regional failure after definitive radiotherapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking, and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between intrapulmonary failure and mediastinal failure to be able to optimize radiotherapy in order to improve loco-regional control even though it is not easy to discriminate between the two sites of failure.Material and methods. This study is a retrospective analysis of 331 NSCLC patients treated with definitive radiotherapy from 2002 to 2011. The patients were treated consecutively at the Department of Oncology, Odense University Hospital, Denmark with at least 60 Gy. All patients were followed in a planned follow-up schedule and no patients were lost for follow-up.Results. At the time of the analysis 93 patients had loco-regional failure only. Of these patients, 68 had intrapulmonary failure only, one patient had failure in mediastinum only, and 24 patients had intrapulmonary failure as well as mediastinal failure. Of the patients which had lung failure only, 78% had mediastinal involvement at treatment start. The only covariate with significant impact on developing intrapulmonary failure only was gross tumour volume. Median survival for the total group of 331 patients was 19 months. The median survival for patients with intrapulmonary failure only was 19 months, and it was 20 months for the patients with mediastinal relapse.Conclusion. We conclude that focus should be on increasing doses to intrapulmonary tumour volume, when dose escalation is applied to improve local tumour control in NSCLC patients treated with definitive radiotherapy, since most recurrences are located here.

Patterns of Locoregional Failure in Stage III Non-Small Cell Lung Cancer Managed With Definitive Chemoradiation Therapy

Patterns of Locoregional Failure in Stage III Non-Small Cell Lung Cancer Managed With Definitive Chemoradiation Therapy

Patterns of Local-Regional Failure in Completely Resected Stage IIIa (N2) Non-Small Cell Lung Cancer Patients: Implications for Postoperative Radiation Therapy Target Volumes

There is a need to evaluate the mediastinal nodal involvement risk based on primary location of tumors and standardize the clinical target volume (CTV) for postoperative radiation therapy (PORT) in completely resected stage N2 patients. Thus we reviewed patterns of locoregional failure for completely resected stage IIIa (N2) patients and examined whether they were consistent with the proposed PORT fields.

Cervical metastases from maxillary squamous cell carcinoma: retrospective analysis and review of the literature

The purpose of this study was to define the incidence of cervical metastasis in squamous cell carcinoma (SCC) of the maxillary alveolus, hard palate and gingiva; to identify patterns of locoregional failure and to assess survival outcomes. We retrospectively analysed 30 patients treated for SCC of the maxillary alveolus and hard palate between 2000 and 2010. Parameters assessed included the incidence of cervical metastasis at presentation and recurrence, paying particular attention to tumour staging and survival outcomes. Of our 30 patients, 25 were confirmed to have T4 SCC of the maxillary alveolus and hard palate with bone invasion. Cervical metastases had been noted in 7 (23%) patients at initial presentation. A total of 9 (36%) patients developed regional failure in the pT4 SCC group shortly after primary resection. Patients with advanced primary SCC of the hard palate and maxillary alveolus (particularly when there was bone invasion) showed high rates of regional failure, and in most cases successful salvage was not achieved. Based on our findings and a review of the existing literature we strongly recommend elective neck dissection for patients with pT4 SCC of the maxillary alveolus and hard palate.

Target volume for postoperative radiotherapy in non-small cell lung cancer: Results from a prospective trial

Background and purposeA previous prospective trial reported that three-dimensional conformal postoperative radiotherapy (PORT) for pN2 NSCLC patients using a limited clinical target volume (CTV) had a late morbidity rate and pulmonary function that did not differ from those observed in pN1 patients treated with surgery without PORT. The aim of this study was to assess locoregional control and localization of failure in patients treated with PORT. Materials and methodsThe pattern of locoregional failure was evaluated retrospectively in 151 of 171 patients included in the PORT arm. The CTV included the involved lymph node stations and those with a risk of invasion >10%. Competing risk analysis was used to assess the incidence of locoregional failure and its location outside the CTV. ResultsOverall survival at 5years was 27.1% with a median follow-up of 67months for 40 living patients. The 5-year cumulative incidence of locoregional failure was 19.4% (95% CI: 18.2–20.5%) including a failure rate of 2% (95% CI: 0–17%) in locations outside or at the border of the CTV. ConclusionsThe use of limited CTV was associated with acceptable risk of geographic miss. Overall locoregional control was similar to that reported by other studies using PORT for pN2 patients.