Patterns Of Locoregional Recurrence Research Articles

Patterns of Locoregional Recurrence after Radical Cystectomy for Stage T3-4 Bladder Cancer: A Radiation Oncologist's Point of View.

PurposeAdjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume.Materials and MethodsWe retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed.ResultsMedian follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2?? patients than in pN0?? patients (15.2% vs. 4.4%, p=0.04).ConclusionPelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.

Locoregional recurrence patterns in women with breast cancer who have not undergone post-mastectomy radiotherapy

BackgroundTo analyze the patterns of locoregional recurrence in breast cancer patients after mastectomy.MethodsThe retrospective study included 7073 women with breast cancer without post-mastectomy radiotherapy: 4604 (65.1%) had pT1–2 N0 disease (low risk); 2042 (28.9%), pT1–2 N1 (intermediate risk); and 427 (6.0%), pT3–4 and/or pN2–3, or pT1–2 N1 after neoadjuvant chemotherapy (high risk). The distribution of cumulative locoregional recurrence was analyzed. The local recurrence and regional recurrence rates were estimated by the Kaplan-Meier method, and differences were compared with the log-rank test. Multivariate analysis was performed using Cox logistic regression analysis.ResultsIn the median follow-up of 63.0 months, 469 patients had locoregional recurrence: chest wall recurrence in 238 (50.7%) cases, supraclavicular/infraclavicular nodes in 236 (50.3%) cases, axilla in 92 (19.6%), and internal mammary nodes in 50 (10.7%) cases. The 5-year local recurrence and regional recurrence rates were 2.5 and 4.4%, respectively. Subgroup analysis of the three risk groups and five molecular subtypes (luminal A, luminal B-Her2 negative, luminal B-Her2 positive, Her2-enriched, and triple negative) also showed that the chest wall and supraclavicular/infraclavicular nodes were the most common recurrence sites. Age, tumor location, T stage, N stage, and hormone receptor status were independent prognostic factors for both local recurrence and regional recurrence (p < 0.05).ConclusionsThe chest wall and supraclavicular/infraclavicular nodes are common sites of locoregional recurrence in breast cancer, irrespective of disease stage or molecular subtype, and the prognostic factors for local recurrence and regional recurrence are similar. Therefore, chest wall and supraclavicular/infraclavicular nodes irradiation should always be considered in post-mastectomy radiotherapy.

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.

Total thyroidectomy with therapeutic level II-IV neck dissection for papillary thyroid carcinoma: level VI recurrence patterns.

Lateral and central compartments cervical lymph nodes metastases are common among patients with papillary thyroid carcinoma (PTC). Elective level VI neck dissection during thyroidectomy and lateral neck dissection (LND) for the treatment of PTC with lateral compartment lymph node metastases is controversial because of the uncertain benefit in clinical outcomes and increased risks of surgical morbidity. We aimed to determine the potential benefit of elective level VI neck dissection in patients with cN1 papillary thyroid carcinoma (PTC) by investigating the rate and pattern of locoregional recurrence in PTC patients who underwent total thyroidectomy and therapeutic lateral node dissection (LND; levels II-IV) without elective level VI dissection. A retrospective cohort study. Data on demographics, clinical presentation and workup, intraoperative and pathological report, postoperative course, adjuvant therapy, recurrence patterns, and overall survival were retrieved from the medical charts of patients who underwent thyroid surgery in our hospital between January 2006 and December 2017. A total of 1415 thyroidectomies were performed during the study period, of which 802 (56.67%) were for PTC. Of those PTC patients, 228 (28.42%) also underwent LND (levels II-VI) during the same thyroidectomy procedure. Thirty-four (14.91%) of those 228 patients, underwent total thyroidectomy with therapeutic lateral ND II-IV without elective level VI ND. During the follow-up period, five (14.7%) of the latter cohort were diagnosed with recurrence in central neck (level VI) lymph nodes, and four of them (11.7%) were diagnosed with ipsilateral recurrence at level VI. Our results revealed 11.7% rate of clinically significant recurrent disease in ipsilateral level VI which, in our opinion, does not justify routine prophylactic level VI ND dissection when the ipsilateral lateral neck is operated for metastases.

Patterns of first recurrence and outcomes in surgically treated women with vulvar cancer: results from FRANCOGYN study group

ObjectiveCancer of the vulva recurrences vary considerably over time and are influenced by several pathological, surgical and adjuvant therapeutic prognostic factors. However, limited information is available about patterns of disease recurrence and prognosis. We analysed patterns of vulvar cancer recurrence based on a large French multicentre database. MethodsData of women with histologically proven squamous cell carcinoma (SCC) and other vulvar cancer treated between 1976 and 2016 were retrospectively abstracted from five institutions with prospectively maintained vulvar cancer databases in France. The endpoints were pattern of recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray’s test) and competing risks regression analysis to estimate sub-distribution hazard ratios and 95% CIs. ResultsIn the whole population, recurrences were observed in 188 of the 617 women (30%) with local-regional, distant and multifocal recurrences in 18% (109/617), 3% (17/617), 10% (62/617), respectively. The median time to recurrence with Interquartile Range (IQR) was 13 months IQR [8–30]. The overall respective 3-years OS and RFS were 78.5% (IC95%: 74.5–82.5) and 75.5% (IC95%: 71.1–80.0). According to FIGO stage, lymph node status and positive lympho-vascular invasion (LVSI), pattern and time of loco-regional and distant recurrence were significantly different. There wasn’t interaction between FIGO stage and LVSI in OS neither RFS (p=0.08 and 0.9 respectively). Conclusion and discussionWe report specific time and site patterns of first recurrence according to FIGO stage, lymph node status and lymphovascular invasion status. Positive LVSI is an important and independent prognostic factor. Defining patterns of recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches.

Failure patterns of locoregional recurrence in women with T1-2N1 breast cancer after modified radical mastectomy

Objective To analyze the failure patterns of locoregional recurrence (LRR) and investigate the range of radiotherapy in T1-2N1 breast cancer patients undergoing modified radical mastectomy. Methods From September 1997 to April 2015, 2472 women with T1-2N1 breast cancer after modified radical mastectomy without neoadjuvant systemic therapy were treated in our hospital. 1898 patients who did not undergo adjuvant radiotherapy were included in this study. The distribution of accumulated LRR was analyzed. The LR and RR rates were estimated by the Kaplan-Meier method, and the prognostic factors were identified in univariate analyses with Log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. Results With a median follow-up of 71.3 months (range 1.1-194.6), 164 patients had LRR, including supraclavicular/infraclavicular lymph nodes in 106(65%), chest wall in 69(42%), axilla in 39(24%) and internal mammary lymph nodes (IMNs) in 19 patients (12%). In multivariate analysis, age (>45 years vs.≤45 years), tumor location (other quadrants vs. inner quadrant), T stage (T1vs. T2), the number of positive axillary lymph nodes (1 vs. 2-3), hormone receptor status (positive vs. negative) were significant prognostic factors for both LR and RR. Conclusions In patients with T1-2N1 breast cancer after modified radical mastectomy, the most common LRR site is supraclavicular/infraclavicular nodal region, followed by chest wall. The axillary or IMN recurrence is rare. The prognostic factors for LR and RR are similar, which indicates that supraclavicular/infraclavicular and chest wall irradiation should be considered for postmastectomy radiotherapy. Key words: Breast neoplasm/modified radical mastectomy; Positive lymph node; Locoregional recurrence patterns

Impact of Oncotype DX Recurrence Score on the Patterns of Locoregional Recurrence in Breast Cancer (Korean Radiation Oncology Group 19-06).

The current study evaluated the impact of the Oncotype DX recurrence score (RS) on the patterns of locoregional recurrence (LRR) in node-negative, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. Totally, 339 patients from 4 institutions were enrolled and analyzed retrospectively. All patients underwent breast-conserving surgery followed by whole-breast irradiation; only 2 patients received regional nodal irradiation (RNI). The RS was < 11 in 55 patients, 11–25 in 241, and > 25 in 43. Sixty-two patients received adjuvant chemotherapy. All patients except 4 received hormonal therapy. During a 62-month median follow-up, local recurrence was observed in 1 patient; regional recurrence, 3; and distant metastasis, 7. All LRRs were observed among patients with a RS > 25, resulting in a 5-year LRR rate of 7.3% in this subgroup. Regional recurrences developed in patients did not receive RNI initially. Thus, RNI might be effective for patients with a high RS.

Evaluation of Locoregional Recurrence Patterns Following Adjuvant (Chemo)Radiotherapy for Oral Cavity Carcinoma

AimsTo evaluate patterns of locoregional recurrence following adjuvant (chemo)radiotherapy for oral cavity squamous cell carcinomas. Materials and methodsOne hundred and one patients who received adjuvant radiotherapy ± chemotherapy for oral cavity squamous cell carcinoma between 2013 and 2016 were analysed. For documented locoregional recurrence, recurrence imaging was deformably co-registered to the planning computed tomography scan. The volume of recurrence was delineated (Vrec). Vrec coverage by 95% of the corresponding planning target volume prescription dose was determined and the location compared with planning target volumes. Sites of recurrence were classified using a combined volume and centroid-based method: (A) central high dose, (B) peripheral high dose, (C) central low dose, (D) central peripheral dose, (E) extraneous. ResultsThe median follow-up was 36 months. Forty-three per cent and 53% of patients received radiotherapy to the ipsilateral neck only and bilateral neck, respectively. Three-year overall survival, disease-free survival, local control, regional control and distant metastases-free survival were 63.0, 65.6, 88.0, 85.1 and 85.3%, respectively. Of 10 episodes of primary site recurrences, five were type A, four type B and one was type E. Of 14 episodes of regional recurrence, five were type A, two type C, two type D and five type E. Five of 21 (24%) patients with oral tongue carcinoma with an undissected/unirradiated contralateral neck had a type E contralateral neck recurrence, including 2/11 with pN0, 1/4 with pN1 and 2/6 with pN2 disease. ConclusionsMarginal and out-of-field recurrences remain a significant pattern of failure. We advocate generous target delineation postoperatively and, for oral tongue carcinomas, a comprehensive approach with bilateral neck irradiation.

A 3-Dimensional CT-Based Analysis of Dosimetric Coverage on the Patterns of Locoregional Recurrence in High-Risk Breast Cancer Patients Treated with Regional Nodal Irradiation

Maximizing dose to regions-at-risk is counterbalanced by efforts to minimize dose to adjacent organs during the treatment planning of locally advanced breast cancer patients. Our goal was to evaluate the association of dosimetric coverage of the target tissues (breast, chest wall, regional nodes) with the incidence of locoregional recurrence (LRR) in breast cancer patients who had been previously treated with RNI. From an institutional database, we identified 57 patients treated for Stage II-III breast cancer between 2000-2014 at single center who developed an isolated LRR following surgery and adjuvant radiation to the breast/chest wall and regional nodes. Eligibility criteria included receipt of conformal RT to the lymph nodes, available DVH data, and radiographic identification of recurrent tumor on imaging scans obtained within 3 months of LRR. Patients with prior distant metastases, recurrence without correlative imaging and prior metastases were excluded. In order to determine the dose coverage in the area of recurrence, we fused the diagnostic chest CT demonstrating recurrence to the original treatment planning CT to create a gross tumor volume-LRR (GTV-LRR). The mean doses to the breast or chest wall, supraclavicular (SCV), Level 1-3 axillary (Ax) and internal mammary nodes (IMN), heart dose (MHD), left anterior descending dose and lung (MLD) were evaluated by DVH. The log-rank test evaluated the association between target coverage and time to the development of LRR. Cox multivariate analysis was adjusted for receptor subtype, receipt of systemic therapy and pathologic stage. A total of 48% of the cohort was comprised of in-breast or chest wall recurrences (BR) and 52% isolated nodal recurrences (NR). Among the NR group, 38% patients received a mean <30 Gy to the GTV-LRR and 62% received mean >30 Gy to the GTV-LRR. The majority of GTV-LRRs in the NR group were in the IMN chain (38%) and axilla (38%), followed by SCV (24%). In the BR group, the association between GTV-LRR and time to LRR was not significant. In contrast, in the NR group, the median time to LRR in patients who received mean<30 Gy GTV-LRR was 7 months , compared to the mean >30 Gy GTV-LRR cohort who failed at a median of 21 months (p=0.03). The mean heart dose in the <30 Gy group was significantly lower, compared to the >30 Gy cohort (p=0.02), indicating that sparing of the heart was prioritized over coverage of target tissues. In this CT-based mapping analysis of LRRs in breast cancer patients previously treated with RNI, the time to development of a nodal recurrence was prolonged by 3-fold when the area had received mean<30 Gy relative to those who had received >30 Gy to the area of eventual recurrence. This study provides proof-of-concept that dosimetric coverage of nodal areas-at-risk should be prioritized in high-risk breast cancer patients receiving radiotherapy.

Chest Wall and Supraclavicular/Infraclavicular Nodal Region are Common Sites of Locoregional Recurrence for Women with Breast Cancer after Mastectomy Irrespective of TN Stage or Molecular Subtypes

To analyze the failure patterns of locoregional recurrence (LRR) and identify the prognostic factors for local recurrence (LR) and regional recurrence (RR) in breast cancer patients after mastectomy. Between 1999 and 2014, 7207 women with breast cancer after mastectomy and axillary dissection were analyzed. All didn’t receive postmastectomy radiotherapy (PMRT). 4671 (64.8%) had pT1-2N0 disease (low-risk), 2078 (28.8%) had pT1-2N1 disease (intermediate-risk) and 458 (6.4%) were defined as high-risk, which included 360 with pT3-4 or pN2-3 disease and 98 pT1-2N1 after neoadjuvant chemotherapy. Among the 5427 patients who had sufficient information to construct molecular subtype, there were 2451 (45.2%) luminal A, 579 (10.7%) luminal B-Her2 negative, 814 (15.0%) luminal B-Her2 positive, 593 (10.9%) Her2 enriched, and 990 (18.2%) triple negative (TN). The distribution of accumulated LRR was analyzed. The LR and RR rates were estimated by the Kaplan-Meier method, and the differences were compared with Log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. With a median follow-up of 62.9 months (6.0-194.6), 481 patients had LRR, including chest wall in 225 (46.8%), supraclavicular/infraclavicular nodes (SCN) in 242 (50.3%), axilla in 96 (20.0%) and internal mammary nodes (IMN) in 52 (10.8%) patients. For LRR patients with low, intermediate and high risk group, 93 (54.1%), 83 (44.9%), 69 (55.6%) had chest wall recurrence, 68 (39.5%), 110 (59.5%), 64 (51.6%) had SCN recurrence, 27 (15.7%), 37 (20.0%), 32 (25.8%) had axilla recurrence, and 28 (16.3%), 20 (10.8%), 4 (3.2%) had IMN recurrence. For LRR patients with luminal A, luminal B-Her2 negative, luminal B-Her2 positive, Her2-enriched, and TN tumors, 48 (45.3%), 23 (56.1%), 25 (43.1%), 25 (57.2%), 61 (58.1%) had chest wall recurrence, 51 (48.1%), 23 (56.1%), 32 (55.2%), 33 (62.3%), 51 (48.6%) had SCN recurrence, 21 (19.8%), 10 (24.4%), 13 (22.4%), 9 (17.0%), 22 (21.0%) had axilla recurrence, and 9 (8.5%), 7 (17.1%), 6 (10.3%), 7 (13.2%), 14 (13.3%) had IMN recurrence. The median interval to LR and RR was 51.6 and 29.2 months. In multivariate analysis, age (≤45 years vs. >45 years), tumor location (inner quadrant vs. other quadrants), T stage (T3-4 vs. T1-2), N stage (pN3 vs. pN2 vs. pN1 vs. pN0), hormone receptor status (negative vs. positive) were significant prognostic factors for both LR and RR (p < 0.05). In breast cancer after mastectomy without PMRT, both chest wall and supraclavicular/infraclavicular nodal region are common sites of LRR, irrespective of TN stage or molecular subtypes. The prognostic factors for LR and RR are similar, which indicates that chest wall and supraclavicular/infraclavicular nodal irradiation should be considered in all patients who planned to receive PMRT.

Recurrence patterns after pancreaticoduodenectomy for ampullary cancer.

Few studies of the oncological outcomes of ampullary cancer have addressed recurrence, and many treatment-related issues remain unresolved. This study evaluated optimal surgical treatment strategies based on recurrence patterns after pancreaticoduodenectomy (PD) for ampullary cancer. Two hundred and fifty-nine patients who underwent PD with R0 resection for ampullary cancer from January 2000 to June 2012 were included. Generally, lymph node (LN) dissection extended to the right superior mesenteric artery (SMA). Recurrence was defined based on imaging studies. The first detected recurrence sites and patterns were analyzed. During a mean follow-up of 51.3months, recurrence occurred in 89 (34.4%) cases, most commonly in the liver. Poor differentiation, advanced T stage, and LN metastasis were identified as risk factors for recurrence. Locoregional and systemic recurrences occurred alone or simultaneously in 20.2%, 73.0%, and 6.7% of patients, respectively. Locoregional and systemic recurrences tended to occur in early- and advanced-stage cases, respectively. A nodal-type recurrence around mesenteric vessels was the most common locoregional recurrence pattern, and 58.8% (10/17) were located left of the SMA. As nodal-type metastasis around the mesenteric vessels was the dominant recurrence pattern, careful LN dissection around the SMA should be considered for early and advanced ampullary cancers.

Pattern of locoregional recurrence after curative resection in pancreatic ductal adenocarcinoma according to the location of the tumor

Pattern of locoregional recurrence after curative resection in pancreatic ductal adenocarcinoma according to the location of the tumor

Intratumoral Heterogeneity of SMAD4 Immunohistochemical Expression and Its Role in Prediction of Recurrence Pattern in Patients with Resectable Pancreatic Cancer.

The aim of our study was to evaluate consistency of SMAD4 expression in different tumor areas and its correlation with recurrence pattern in patients after resection for pancreatic cancer (PC). Records of patients who underwent resection for nonmetastatic PC between 2001 and 2015 were analyzed. Formalin-fixed, paraffin-embedded tissue sections from different areas of primary tumor and lymph node metastases were analyzed immunohistochemically (IHC) for SMAD4 expression using TMA technology. SMAD4 expression was assessed in 356 tissue sections obtained from 91 patients. SMAD4 expression was positive in all assessed tumor slides only in 7 of 26 patients (26.9%). There were 54 recurrences (9 locoregional, 41 distant, and 4 both local and distant) with median follow-up of 21.7months. There was no correlation between SMAD4 expression and locoregional recurrence pattern (p = 0.30). SMAD4 status influenced neither distant recurrence-free survival (p = 0.99) nor overall survival (p = 0.13). Different areas inside primary tumor and lymph node metastases express SMAD4 heterogeneously. SMAD4 IHC expression is not a biomarker of the recurrence pattern after surgical resection for PC.

Suggestions for surveillance and radiation strategy in nasopharyngeal carcinoma treated with IMRT: Based on hazard-rate and patterns of recurrence

ObjectiveThe study was designed to appraise the locoregional recurrence patterns using conventional two-dimensional radiotherapy (2D-RT) and intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC) in order to better establish the scenario of the modern radiotherapy and the duration of surveillance. Materials and MethodsWe reviewed the institutional database to identify patients with pathologically confirmed, non-metastatic NPC who completed radical 2D-RT or IMRT at our center from 2000 to 2011. We collected data on clinicopathologic features, treatments and outcomes. Statistical analyses were performed using SPSS 20.0 or STATASE 14.0. ResultsThe median follow-up was 60.1 months. Of 2315 patients, 1289 (53%) were treated with 2D-RT and 1026 (47%) with IMRT. IMRT group achieved better locoregional control rate, with the 5-year locoregional relapse-free survival (LRRFS) were 84.9% and 87.7% among patients received 2D-RT and IMRT, respectively (P = 0.050). IMRT was superior to 2D technique in terms of local relapse-free survival (LRFS) (88.4% vs 91.1%, P = 0.047) and the advantage was only significant in T3-4 subgroup (81.6% vs 90.2%, P = 0.000). Similar neck control rates were observed using different RT techniques. And the recurrence time appeared to be postponed by IMRT, with peaks accounting for the year 1.5 and year 3–4 compared to which was predominant at the first two years using 2D-RT in nature. ConclusionsIMRT provided an improved LRRFS in overall stage and LRFS in advanced T stage for NPC compared with 2D-RT. Annual hazard of recurrence also changed with RT techniques.

Mapping patterns of locoregional recurrence following contemporary treatment with radiation therapy for breast cancer: A multi-institutional validation study of the ESTRO consensus guideline on clinical target volume

Background and purposeTo validate the ESTRO guideline on clinical target volume (CTV) delineation for breast cancer using a multi-centre dataset. Materials and methodsPatients with axial imaging of gross locoregional recurrence (LRR) were identified from 10 participating institutions. All patients received RT, albeit not to all regional node. The location of LRR was transferred to the corresponding area on representative axial computed tomography images and compared with ESTRO-CTV. ResultsThe locations of LRRs in 234 patients with 337 recurrence lesions were mapped. The ESTRO-CTV encompassed 97.6% of all LRRs, except in lymph node level 4 and the pectoralis muscle. Although 8.8% of level 4 failures occurred outside the ESTRO-CTV, cranial to the subclavian artery, all nodes were located within 6 mm cranially. Another 20% occurred posterolateral to anterior scalene muscles; however, 11/16 cases had simultaneous multiple lymph node recurrences, and 8/16 initially had N2-3 tumours. Local recurrence at the pectoralis muscle was prominent in patients undergoing mastectomy but not breast-conservation surgery (28% vs. 2.9%, P = .001). ConclusionsOur mapping data demonstrated that the ESTRO-CTV, with some considerations, successfully encompassed most LRRs in patients undergoing contemporary management, thus validating ESTRO-CTV to be valuable for highly conformal radiation therapy techniques.

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.

Pattern of locoregional recurrence after curative resection in pancreatic ductal adenocarcinoma according to the location of the tumor

Pattern of locoregional recurrence after curative resection in pancreatic ductal adenocarcinoma according to the location of the tumor

Analysis of CT-verified loco-regional recurrences after definitive IMRT for HNSCC using site of origin estimation methods

Introduction: A significant part of patients with head and neck squamous cell carcinoma (HNSCC) develop recurrent disease after curative radiotherapy. We aimed to analyze loco-regional recurrence pattern by identifying possible points of recurrence origin by three different methods in relation to treatment volumes.Material and methods: A total of 455 patients completed IMRT-based treatment for HNSCC from 2006 to 2012. A total of 159 patients had remaining cancer after IMRT, developed loco-regional recurrence or distant disease during follow-up. Among those, 69 patients with loco-regional recurrences had affirmative CT or PET/CT scan. Possible points of origin (POs) of the recurrences were identified on scans by two independent observers, estimated as center of mass and as maximum surface distance. The recurrence position was analyzed in relation to high-dose treatment volume (CTV1) and 95% of prescription dose.Results: In total, 104 loco-regional recurrences (54 in T-site and 50 in N-site) were identified in 69 patients. Median time to recurrence for the 69 patients was 10 months. No clinically relevant difference was found between the four POs, with standard deviation between POs in x, y and z axes of 3, 3 and 6 mm. For recurrences inside CTV1, 0–5 mm and 5–10 mm outside CTV1 the standard deviation of dose differences between the POs were 1, 1.4 and 1 Gy, respectively. 56% and 25% of T-site and N-site recurrences were inside CTV1, respectively. Coverage by 95% prescription dose to high-dose treatment volume was achieved in 78% of T-site and 39% of N-site recurrences.Conclusions: For recurrences identified by possible points of recurrence origin, no significant difference between observer-based or mathematically estimated methods was found. More than half of T-site recurrences were inside high-dose treatment volume, whereas N-site recurrences were mainly outside.

LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-Mediated H3K4me2 demethylation

BackgroundAlthough the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human gastric cancers development. Our previous studies suggest that HOTAIR contributes to gastric cancer development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we investigated the characteristic of the LncRNA FEZF1-AS1 in gastric cancer.MethodsQRT-PCR was used to detect the expression of FEZF1-AS1 in gastric cancer tissues and cells. MTT assays, clonogenic survival assays and nude mouse xenograft model were used to examine the tumorigenesis function of FEZF1-AS1 in vitro and in vivo. Bioinformatics analysis were used to select downstream target genes of FEZF1-AS1. Cell cycle analysis, ChIP, RIP,RNA Pulldown assays were examined to dissect molecular mechanisms.ResultsIn this study, we reported that FEZF1-AS1, a 2564 bp RNA, was overexpressed in gastric cancer, and upregulated FEZF1-AS1 expression indicated larger tumor size and higher clinical stage; additional higher expression of FEZF1-AS1 predicted poor prognosis. Further experiments revealed that knockdown FEZF1-AS1 significantly inhibited gastric cancer cells proliferation by inducing G1 arrest and apoptosis, whereas endogenous expression FEZF1-AS1 promoted cell growth. Additionally, RIP assay and RNA-pulldown assay evidenced that FEZF1-AS1 could epigenetically repress the expression of P21 via binding with LSD1, the first discovered demethylase. ChIP assays demonstrated that LSD1 could directly bind to the promoter of P21, inducing H3K4me2 demethylation.ConclusionIn summary, these data demonstrated that FEZF1-AS1 could act as an “oncogene” for gastric cancer partly through suppressing P21 expression; FEZF1-AS1 may be served as a candidate prognostic biomarker and target for new therapies of gastric cancer patients.

Three-dimensional analysis of patterns of locoregional recurrence after treatment in breast cancer patients: Validation of the ESTRO consensus guideline on target volume

Background and purposeTo explore the validity of the ESTRO-clinical target volume (CTV), we conducted three-dimensional analyses of locoregional recurrence (LRR) patterns according to the ESTRO- and RTOG-CTVs. Moreover, we explored which factors contribute to metastasis development outside the recommended CTV. Materials and methodsWe identified patients with post-treatment LRR explicitly exhibited on computed tomography (CT) images. All recurrences on CT were overlaid on representative CT images at the equivalent location, based on reference anatomic structures. ResultsA total of 235 recurrent lesions were identified in 129 patients. We depicted all LRR patterns in relation to the ESTRO- and RTOG-CTVs on CT and maximum intensity projection images. The ESTRO-CTV successfully contained the extent of the LRR within the RTOG-CTV in 96.4% of all early-stage breast-conserved women. Geographic misses of local recurrence were frequently observed in mastectomy patients (P=.002) and tended to originate from deep, but thin, chest walls. The rate of geographic misses of regional recurrence was low (3.6%) at the early stage, but increased in patients aged <45years and with triple-negative tumors (P<.05). ConclusionsApplication of the ESTRO-CTV in early-stage disease seems justified.