Regional Relapse Research Articles

FDI inflows and intellectual property rights for MNEs in emerging markets: an alternative approach through the lens of trademarks in Vietnam (1986-2016)

PurposeWhile the current anti-globalisation wave is considered as a regional and cyclical relapse among Western countries, the new era of globalisation has shifted away from stagnant developed economies towards the rising prosperity of emerging Asia, where it is attracting substantial global inward foreign direct investment (FDI). Focussing on Vietnam, the country that is seen as Asia’s next economic tiger, the question of how important intellectual properties (IP) protection is in the international competition for FDI inflows is still unsettled, especially on the under-researched topic of trademarks.Design/methodology/approachThis paper takes on the business history approach, which allows rich evidence from the dynamic and evolving natures of multinational enterprises (MNEs) to drive the research process, so that international business scholars can test models rigorously. The evidence provided in this paper is essentially qualitative and combines trademark registrations data, with trade and FDI statistics between 1986 and 2016, also draws on companies’ archives, industry reports and related newspaper articles.FindingsThis paper provides the chronology of intellectual property right (IPR) legal landscapes and the dynamic co-evolution of trademarks and FDI inflows in Vietnam. Three trademark protection strategies for MNEs and their patterns here are addressed. The paper also argues that trademarks bring new insights and IP protection strategy for pharmaceutical MNEs for the case of Vietnam is as important in trademarks as it is in patents. In emerging markets with strong incentives for FDI such as Vietnam, MNEs are not necessarily put off by weak IPR, but rather create alternative strategies for dealing with the lack of IP protection in these emerging market settings.Originality/valueThis study challenges the stream of thoughts that view trademarks as a “neglected intangible asset” among different IPRs, while in fact, trademarks advance MNEs’ knowledge by ensuring competitiveness and long-run survival in emerging markets. This paper is among the first few attempts to look at pharmaceutical industry through the lens of trademarks, moving away from the traditional patent-focussed approach. It extends the understanding of OLI paradigm and highlights that MNEs need to possess Oa and Op advantages not only at the beginning of internationalisation process but rather evolving through the time to cope with imitation risks in the host country.

Mapping of Regional Failures After Definitive Radiotherapy in Patients with Locally Advanced Cervical Esophageal Carcinoma.

PurposeThis study aimed to retrospectively analyze the failure patterns and clinical outcomes in patients with locally advanced cervical esophageal carcinoma (CEC) after definitive radiotherapy (RT), and illustrate the mapping of regional failures.Patients and MethodsWe reviewed 82 patients with CEC confirmed as squamous cell carcinoma who had completed definitive RT from August 2008 to December 2017. Data on clinical characteristics were collected from the medical records system. Patterns of treatment failures and the survival follow-up were analyzed.ResultsThe median age was 58 (38–78) years. In 37 patients, the lesions were limited to the cervical esophagus, while in the remaining 45 patients, the disease got beyond the cervical esophagus (pharynx or thoracic esophagus involved). While 10 patients had stage Ⅱ disease, 72 had stage III disease. The completed median dose for 95% PGTV and 95% PTV was 66 Gy and 58 Gy. While the median follow-up was 27.6 months, the median progression-free survival (PFS) and overall survival (OS) was 16.1 and 28.3 months, respectively. The 3-year PFS and OS was 30.3% and 45.3%, respectively. Treatment failures were reported in 55 patients, of which 22, 8, 7, 9, 2, 3, and 4 patients had developed local, regional, distant, local-regional, regional-distant, local-distant and local-regional-distant failure, respectively. Of the 41 relapsed nodal sites, 28 were located “in-field” whereas 1 was “marginal” and 12 were “out-field”. The most frequent regional relapses were at level VIb, IV and the upper-middle mediastinum.ConclusionRegional recurrences focused on lower neck and upper-middle mediastinum, and mainly “in-field”, after definitive RT in patients with CEC.

Prophylactic thoracic duct ligation is associated with poor prognosis and regional lymph node relapse in esophageal squamous cell carcinoma.

The ligation of thoracic duct interrupts the normal lymphatic circulation. Whether the ligation of thoracic duct would affect tumor recurrence and patient survival is unclear. The correlations between prophylactic thoracic duct ligation (PLG) and prognosis were examined in patients with esophageal squamous cell carcinoma. Patients who received Ivor Lewis or McKeown esophagectomy with systemic lymph node dissection and R0 resection between 2003 and 2013 in Sun Yat-sen University Cancer Center were included in the study. A total number of 473 and 462 were included in the PLG group and non-prophylactic thoracic duct ligation (NPLG) group, respectively. The PLG group had a lower 5-year survival rate (48.2% vs 61.6%, P < .001). After a 1:1 propensity score matching, 874 cases (437 pairs) were included and the survival analysis showed that PLG was associated with worse 5-year cumulative survival of 48.6% vs 61.6% in those patients without ligation (P < .001). The multivariate analysis revealed that PLG was an independent factor for poor prognosis after esophagectomy (hazard ratio, HR = 1.56; 95% confidence interval, 95% CI, 1.26-1.93, P < .001). Additionally, PLG was associated with regional lymph node relapse (P = .015). PLG should not be performed routinely if no sign of thoracic duct rupture or tumor invasion were identified.

Treatment Outcome and Patterns of Failure in Patients with Maxillary Sinus Cancer: Clinical Experience from a Regional Cancer Centre in North India.

Treatment of maxillary sinus cancer poses several challenges because of its complex anatomy, close proximity to critical structures and majority of patients presenting at an advanced stage. Despite presence of several treatment approaches, the outcome in these cancers has remained dismal. This article examines its clinical behaviour and treatment outcome of these patients treated at our centre in past 7years. In this retrospective study, 67 patients with carcinoma of maxillary sinus presented from January 2011 to December 2017 were analysed. All the patients reporting during this period were included except those who did not turn up after first visit. Of all the patients, 64.2% had squamous cell carcinoma. The majority of patients presented with advanced stage (IVA and IVB, 83.58%). Nodal disease at presentation was seen in seven patients (10.4%). Treatment to the primary site comprised of surgery and radiotherapy in 24 patients, radiotherapy alone in 22 patients and surgery alone in 12 patients. Statistical program for social sciences (SPSS) version 16 was used for all statistical analyses. The mean follow-up time was 25months (range 3-72months). Overall, 17 out of 41 patients who were treated with curative intent (41.5%) developed recurrence. Patients who underwent surgery followed by adjuvant radiotherapy did fairly better in terms of recurrence. Seven patients out of 17 (41.2%) could be salvaged by surgery or radiation. Only one patient developed distant metastasis to D8 vertebra. Patients who were treated with surgery and radiotherapy (either preoperative/adjuvant setting) had better disease-free survival. The results of the current study regarding the treatment of carcinoma of the maxillary sinus show feasibility and efficacy of multimodal therapy. Radical radiotherapy appears to be a feasible alternative in cases of inoperable tumours. Loco regional relapse remains a significant pattern of failure.

Individualized Prophylactic Neck Irradiation in Patients with cN0 Head and Neck Cancer Based on Sentinel Lymph Node(s) Identification: Definitive Results of a Prospective Phase 1-2 Study

This prospective, nonrandomized, interventional phase 1-2 study investigated the individualization of elective node irradiation in clinically N0 head and neck squamous cell carcinoma by sentinel lymph node (SLN) mapping with single-photon emission computed tomography/computed tomography (SPECT/CT) and its impact on tumor control and radiation-related toxicity. Forty-four patients with clinically N0 head and neck squamous cell carcinoma treated with definitive (chemo-)radiation therapy were imaged with SPECT/CT after 99mTc nanocolloid injection around the tumor. The neck levels containing up to the 4 hottest SLNs were selected for prophylactic irradiation. A comparative virtual planning was performed with the selection of neck levels based on the current international guidelines. Regional control was monitored as a function of the selected volume. Dosimetric data for the organs at risk were compared between the plans. Normal tissue complication probability (NTCP) rates were derived for xerostomia, dysphagia, and hypothyroidism to predict the clinical benefit and correlated to quality-of-life (QoL) assessments at 6 months. Sixteen percent of patients presented unpredicted lymphatic drainage, and 48% drained unilaterally. The nodal clinical target volume based on lymphoscintigraphy was smaller than the nodal clinical target volume based on international guidelines by a factor of 2 (P < .0001). After a median follow-up of 46 months, only 1 patient experienced a regional relapse in a nonirradiated area. Significant median dose reductions to organs at risk were observed, particularly to contralateral salivary glands in patients with unilateral drainage (14.6-28.1 Gy) and to the thyroid gland in all patients (22.4-48.9 Gy). Median NTCP reductions were observed for xerostomia (0.3% to 13.7%), dysphagia (1.7% to 10.8%), and hypothyroidism (14.0% to 36.1%). QoL at 6 months was improved, particularly in patients irradiated unilaterally. Neck SLN mapping with SPECT/CT individualizes and reduces the elective nodal target volumes without compromising the regional control. The NTCP rates were reduced and favorable QoL were observed in all patients, particularly in the case of unilateral irradiation.

Analysis of expression of molecular marker KI-67 in patients with laryngeal cancer for regional metastases and recurrences

Background: Laryngeal cancer is a common localization of squamous cell carcinoma of the head and neck. The main factor influencing the survival of patients is the presence of regional metastases. The malignant degeneration of a cell is always accompanied by disruption of the cell cycle, in particular a sharp increase in proliferative activity. The molecular marker Ki-67 is used to investigate the proliferative activity of tumor cells. Aim of the study: To study the informative content of immunohistochemical investigation and to determine the expression of the molecular marker Ki-67 in patients with laryngeal cancer, prior to the prediction of regional metastasis and relapse. Materials and Methods: 70 patients with cancer, stage III-IV (T3-4N0-3M0) clinical group II were under observation. Of these, 39 patients from the main group were with regional laryngeal cancer metastases, and 31 patients in the comparison group – without revealed regional metastases. Patients' age ranged from 33 to 74 years. The average age was 61.9 years. Male patients made up the absolute majority of 99% No = 69. All patients were histologically diagnosed with squamous cell carcinoma. Monoclonal antibodies to Ki67 (TermoScientific, USA) were used as the primary molecular markers. The proliferation index (PI) was rated as low in the range of 0-30% and as high in more than 30% of positive cells with an intranuclear label. Results: The study of molecular markers Ki-67 showed its expression at 69 [60.2; 77.5]% (Me [25%; 75%]) for the squamous cell laryngeal cancer group, without metastases – 60 [29; 70.5]%, for the group with metastases – 72 [67; 80]% (P &lt;0.001). In statistical data processing, the AUC value (0.777) was set for Ki-67 for metastasis and showed an increased degree of expression for laryngeal cancer metastasis. Ki-67 has a good diagnostic value and can be used as an additional method for predicting regional laryngeal cancer metastases. However the practical use of this marker as a prognostic one for determining the volume of surgery on the lymphatic structures of the neck requires further investigation. It should be noted that this study did not reveal the link of Ki-67 AUC (0.588) with the degree of differentiation of laryngeal cancer and its recurrence, but more in-depth study of molecular markers in the future may reveal other patterns of tumor growth and be used in the prognosis and personalization of treatment. Conclusion: Expression of Ki-67 allowed to accurately predict tumor metastasis. A 1% increase in Ki-67 expression resulted in an 8.3% increase in the chance of tumor metastasis (95% CI - 1.043-1.142), and the age dependence on metastasis is not reliable. Determination of expression of Ki-67 does not accurately predict the possibility of recurrence of laryngeal cancer (p=0.27; AUC (95% CI) – 0.588 (0.414-0.763)) herewith age dependence of chance of a recurrence was not revealed.

Indicators for secondary carcinoma in head and neck cancer patients following curative therapy: A retrospective clinical study.

Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for local and regional relapse, as well as for occurrence of synchronous or metachronous secondary carcinoma. The aim of this retrospective study was to evaluate the frequency of secondary malignancies amongst HNSCC patients and their association with age, sex and TNM classification, as well as smoking and alcohol abuse. Data from 394 patients with HNSCC who were treated at the Department of Otorhinolaryngology-Head and Neck Surgery of the University Hospital Mannheim between 2011 and 2015 were retrieved and analyzed using t-tests and P≤0.05 was considered statistically significant. Of the 394 patients, 50 (12.7%) developed a secondary carcinoma. In this cohort, >70% of secondary malignancies were diagnosed using clinical inspection or microlaryngoscopy. The majority of secondary malignancies were identified in the oropharynx, with men being more often affected overall. Continued abuse of carcinogenic substances appeared to increase the incidence of secondary carcinoma, whereas the localization of the primary tumor, age, sex or TNM classification were not identified as significant indicators of the occurrence of a secondary carcinoma. The purpose of the present study was to emphasize the importance of intensive follow-up to ensure early detection of secondary malignancies. The aim was to help predict numbers and occurrence within smaller cohorts, and to evaluate the quality of data collected during the establishment of a certified tumor center. To fully evaluate the role of continued exposure to noxious substances and other possible contributing factors, and in order to improve the rate of early diagnosis and establish preventive strategies, multicentered studies with larger cohorts are required.

Cost-effectiveness of six months versus 1-year adjuvant trastuzumab in HER2 positive early breast cancer in Egypt

Introduction: Breast cancer is the most prevalent cancer among women in Egypt. Trastuzumab is administered with chemotherapy for patients with HER2-positive advanced breast cancer (HER2 + ve ABC) in the metastatic and adjuvant settings resulting in improved treatment outcomes, and long-term follow-up. Some studies have evaluated whether equivalent outcomes can be achieved with reduced treatment duration. This study evaluates the cost-effectiveness of 6-month versus 1-year trastuzumab treatments from payer perspective over a 10 year time horizon.Methods: A half-cycle corrected Markov model was developed with five mutually exclusive health states; patient with HER2 +ve ABC, disease-free survival (DFS), local or regional relapse, metastatic relapse, and death. A cycle length of 6 months was applied, direct medical costs including cost of treatments, day-care, surgery, health states and follow-up visits were collected, and indirect costs such as lost productivity were not estimated. The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted.Results: Among the HER2 +ve ABC patient population in Egypt, the total QALYs of the 6-month trastuzumab were estimated to be 2.99 compared with 2.93 for the 1-year trastuzumab which resulted in a difference of 0.06 QALYs. The total costs were EGP 271,647 ($106,947) and EGP 381,248 ($150,097), respectively. These costs yielded an ICER of –109,600 EGP/QALY (–43,149 $/QALY) for the 6-month trastuzumab. The 6-month trastuzumab is a dominant strategy when compared to 1-year trastuzumab, resulting in improved effectiveness at a reduced cost. All analyses results confirmed the dominance of 6-month trastuzumab and our model robustness.Conclusions: This study concluded that 6-month trastuzumab is a cost-effective option when compared to 1-year trastuzumab in patients with HER2 +ve ABC in Egypt. Our findings provide health care decision makers with additional insights to best allocate available resources concurrently with the improvement of the Egyptian patient’s outcomes.

Abstract OT3-01-02: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study

Abstract Introduction Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients with negative SLNs without jeopardizing survival or regional control. International guidelines keep recommending ALND in the presence of positive (+) SLNs. However SLN is the only site of axillary metastasis (MTS) in many cases (60%). Retrospective studies have also shown a low risk of locoregional relapse in patients with SLNs+ not receiving ALND.This latter finding was recently confirmed in a randomized trial comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+. However the observation of both similar relapse rate and survival in the 2 arms and the conclusion of a non-inferiority of SLNB compared to ALND require cautiousness because of some study limitations: premature enrollment cessation due to death rate lower than expected, short follow-up (6 years), small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (&amp;gt;90%) which irradiates the breast but also the I° axillary level, thereby contributing to the low rate of regional relapse in the SLNB arm due to lymph node sterilization. Consequently further randomized trials with more precise selection criteria based on homogeneous clinico-pathological features and with longer follow-up are needed to confirm that performing only SLNB does not affect survival or relapse risk in patients with 1-2 SLNs+. Materials and Methods Primary and secondary aims of the present 2-arm randomized trial are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse, respectively, thus evaluating whether SLNB is or is not inferior to ALND. Patients receive either conservative surgery or mastectomy and radiotherapy. They all undergo intraoperative SLNB and SLN evaluation, and are randomly assigned to either further dissection of level I-II axillary lymph nodes (standard ALND arm) or absence of any axillary surgery (experimental SLNB arm). According to International Guidelines post-surgery treatments. Eligibility criteria are: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 SLNs presenting macroMTS at intraoperative or definitive histological evaluation; no distant MTS; no neoadjuvant therapy; no previous invasive BC, signed informed consent. Exclusion criteria are: in situ, inflammatory, contralateral BC; presence of only microMTS in the SLN+; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. Follow-up controls foresee: clinical examination every 6 months for 5 years and yearly thereafter; annual mammography and breast echography; annual axillary echography for patients in the SLNB arm; additional laboratory and instrumental surveys in case of suspected onset of distant MTS. The primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and to locoregional (ipsilateral breast or axillary, internal mammary or sopraclaveolar lymph nodes) disease recurrence. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Citation Format: Corrado Tinterri, Emilia Marrazzo, Federico Frusone, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-02.

Elective neck treatment in sinonasal undifferentiated carcinoma: Systematic review and meta-analysis.

Sinonasal undifferentiated carcinomas (SNUCs), being an aggressive malignancy with dismal survival outcome, have given limited consideration regarding management of regional failures. A total of 12 studies, published between 1999 and 2019, met inclusion criteria. We performed a meta‐analysis assessing regional (neck) relapse after elective neck treatment compared to observation in clinically node negative (N0) necks. Clinical data of 255 patients were used for meta‐analysis. Among them, 83.4% of patients presented with T4 tumors and 14.1% had positive neck nodes. Elective neck treatment was applied in 49.5% of analyzed patients. Regional relapses occurred in 3.7% of patients who have undergone elective neck treatment compared to 26.4% in patients who had not. Elective neck treatment significantly reduced the risk of regional recurrence (odds ratio 0.20; 95% confidence interval 0.08‐0.49; P = .0004). The meta‐analysis indicates that elective neck treatment could significantly reduce the risk of regional failures in patients with SNUCs.

Time-varying pattern of recurrence risk for localized melanoma in China

BackgroundAcral and mucosal melanomas are rarely seen in Caucasians but common in China. There are limited data on the recurrence characteristics for these patients. This study aimed to identify the recurrence pattern for localized melanoma in China, especially acral and mucosal subtypes.MethodsPatients with localized melanoma who underwent radical resection between January 1999 and December 2014 in southern China were retrospectively reviewed. Survival and annual recurrence hazard were analyzed by Kaplan–Meier method and hazard function, respectively.ResultsTotally, 1012 patients were included (acral melanoma 400; chronic sun-induced damage (CSD)/non-CSD melanoma 314; mucosal melanoma 298). Recurrence was recorded in 808 patients (localized 14.1%; regional 29.6%, and distant 56.3%). Mucosal melanoma had local and M1c stage recurrence more frequently than cutaneous melanoma, but less frequent regional node relapse. There was no difference in recurrent site distribution between acral and CSD/non-CSD melanoma. The annual recurrence hazard curve for the entire cohort showed a double-peaked pattern with the first major peak in the second year after surgery and the second peak near the seventh year. Mucosal melanoma had a higher recurrence risk than cutaneous melanoma. Acral melanoma had a lower flat recurrence peak than CSD/non-CSD melanoma. Tumor thickness > 4.0 mm, ulceration, positive regional nodes, and wound infection were associated with a higher recurrence risk in cutaneous melanoma. Adjuvant therapy reduced the recurrence risk of cutaneous melanoma but not of mucosal melanoma.ConclusionsThis is a large cohort about the rule of recurrence risk in acral and mucosal melanoma and will provide an initial framework for development of surveillance and adjuvant strategy for Chinese melanoma patients.

Patterns of First Relapse and Outcome in Patients with Locally Advanced Cervical Cancer After Radiochemotherapy: A Single Institutional Experience

Radiochemotherapy followed by brachytherapy is the standard treatment in locally advanced cervical cancer. The aim of this study was to evaluate the patterns of first relapse, the treatment given and its outcome. This is a retrospective analysis of electronic records of locally advanced cervical cancer patients treated in prospective trials from 2003 to 2014. Out of 1388 patients, relapse was seen in 316 (23%). Relapse was seen as—pelvic: 105 (7.6%), distant: 136 (10%), and both: 75 (5.4%). Local, regional, paraaortic and systemic relapses were seen in 148 (10.8%), 65 (4.7%), 102 (7.4%) and 163 (11.8%) patients, respectively. Post-relapse, 201/316 (63.6%) received palliative care alone. Treatment in the form of concurrent or sequential chemo-radiotherapy, surgery, stereotactic body radiotherapy and reirradiation using brachytherapy was received by 15 (4.7%), 7 (2.2%), 1 (0.3%) and 1(0.3%) patients, respectively; 65 (20.6%) received palliative chemotherapy, and 28 (8.9%) received palliative radiotherapy. Median post-relapse survival was 7 months (95% CI 5.9–8.1); and in those who received treatment versus supportive care was 10 (95% CI 7.0–13.0) versus 5 (95% CI 3.9–6.1) months (p 1-year post-relapse survival was 85.7% in surgery, 66.7% in concurrent or sequential chemotherapy plus radiation, 32.3% in palliative chemotherapy, 14.3% in palliative radiotherapy and 13.4% in supportive care. Distant failure is the predominant pattern of relapse seen in patients undergoing radiochemotherapy for locally advanced cervical cancer. Well-selected single-site relapses treated with surgery or chemotherapy plus radiation can have good post-relapse survival.

RADIOTHERAPY OF PROSTATE CANCER: PRIMARY RADIOTHERAPY AND RADIOTHERAPY IN DISEASE RELAPSE.

SUMMARYRadiotherapy presents one of the essential modes of treatment in patients with prostate cancer at almost any stage of the disease. It can be delivered as external beam radiotherapy, as brachytherapy or two methods combined. Higher radiation doses are proven to be more effective than low doses and moderate hypofractionation with doses up to 3.4 Gy per fraction is proven equivalent to standard fractionation using 1.8- 2 Gy per fraction. Stereotactic body radiotherapy (SBRT) with doses from 3.4 to 7.25 Gy per fraction presents valuable option in certain subgroups of patients. In case of local regional disease relapse, radiotherapy is used in curative setting.

Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma

PurposeOur purpose was to describe the patterns and predictors of treatment failure in patients receiving definitive chemoradiation therapy (CRT) for anal squamous cell carcinoma (ASCC), delivered using intensity modulated radiation therapy (IMRT).Methods and MaterialsOur study was a retrospective cohort analysis of consecutive patients treated with curative intent for ASCC using CRT delivered with a standardized IMRT technique in 5 UK cancer centers. Patients were included from the start of UK IMRT guidance from February 2013 to October 31, 2017. Collected data included baseline demographics, treatment details, tumor control, sites of relapse, and overall survival. Statistical analysis to calculate outcomes and predictive factors for outcome measures were performed using SPSS and R.ResultsThe medical records of 385 consecutive patients were analyzed. Median follow-up was 24.0 months. Within 6 months of completing CRT, 86.7% of patients achieved a complete response. Three-year disease-free survival and overall survival were 75.6% and 85.6%, respectively. Of all relapses, 83.4% occurred at the site of primary disease. There were 2 isolated relapses in regional nodes not involved at outset. Predictive factors for cancer recurrence included male sex, high N-stage, and failure to complete radiation therapy as planned.ConclusionsThe treatment results compare favorably to published outcomes from similar cohorts using 3-dimensional conformal CRT. The observed patterns of failure support the current UK IMRT voluming guidelines and dose levels, highlighting our prophylactic nodal dose as sufficient to prevent isolated regional relapse in uninvolved nodes. Further investigation of strategies to optimize CR should remain a priority in ASCC because the site of primary disease remains the overwhelming site of relapse.

Sentinel node biopsy and lymph node dissection in the era of new systemic therapies for malignant melanoma

Recently, adjuvant therapies with checkpoint inhibitors and BRAF/MEK inhibitors have become available for patients with malignant melanoma and microscopic nodal disease. Meanwhile the number of complete nodal dissections for amelanoma-positive sentinel node (SN) have decreased significantly. The authors discuss the significance of sentinel node biopsy (SNB) and early lymph node dissection in the era of adjuvant systemic therapy for stageIII melanoma. Current publications and recommendations were evaluated. Complete nodal dissection for apositive SN significantly reduces the risk of regional nodal relapse. However, neither SNB nor complete nodal dissection following apositive SN are associated with abenefit in survival. With the availability of novel adjuvant systemic treatment strategies for stageIII melanoma, SNB has become an even more important part of modern staging diagnostics. Thus, detection of early dissemination of melanoma cells into the SN as well as the quantification of the tumor load are decisive for further therapy planning. Accurate assessment of the regional lymph node status by SNB is becoming even more important in the era of novel effective adjuvant therapies for microscopic nodal disease. Whether complete lymph node dissection is performed in patients with apositive SN needs to be assessed individually. In the case of "active nodal surveillance" instead of surgery, long-term close follow-up in specialized centers, including ultrasonographic controls, is required.

P2.17-20 A Radiomic Approach to Predict Nodal and Distant Relapse in Patients Treated with Stereotactic Body Radiation Therapy for Early Stage NSCLC

Regional and distant relapse remain a significant issue in the treatment of early stage non small cell lung cancer with Stereotactic Body Radiation Therapy (SBRT). There is a need for predictive biomarkers able to identify patients that are at higher risk of relapse. In this work we present a radiomic approach using features extracted by routine planning CT, to predict the risk of nodal and distant recurrence. A cohort of 102 patients was retrospectively investigated. All patients were affected by early stage (T1-T2) lung cancer and received the same radiation treatment with 48Gy delivered in 4 fractions. For all patients, a set of 45 radiomics textural features was computed for the tumor volumes segmented on the treatment planning CT images. Patients were split into two independent cohorts used for training (70% of cases) and validation (30% of cases). A stepwise backward linear discriminant analysis (LDA) was applied as a classifier to identify patients at risk of lymph-nodal progression. The performance of the model was assessed by means of standard metrics derived from the confusion matrix. Furthermore, all textural features were correlated to survival data to build predictive models: the features/predictors found significant at univariate analysis and to elastic net regularization, were included in a multivariate model to predict disease specific progression free survival (PFS) and disease specific survival (DS OS). Low and high risk groups were identified by maximizing the separation by means of the Youden method. In the total cohort (77 (75.5%) males and 25 (24.5%) females, median age 76.6 years), 15 patients presented nodal progression at the time of analysis (11 in the training and 4 in the validation sets); 19 patients (18.6%) died because of disease specific causes, 25 (24.5%) died for other reasons, 28 (27.5%) were alive without disease and 30 (29.4%) with either local or distant progression. The mean tumor volume was 5.6±6.4cm3. Figure 1 illustrates the actuarial curves for PFS and DS OS over the entire training and test cohorts (in both cases the difference was not significant) and the same data stratified in low and high risk groups identified. In all case highly significant differences were identified. Radiomics features extracted from treatment planning CT images can distinguish patients with low and high risk of tumor progression and disease specific death in early stage lung cancer treated with SBRT.

Association between single nucleotide polymorphisms within HLA region and disease relapse for patients with hematopoietic stem cell transplantation

Disease relapse occurs in patients with leukemia even hematopoietic stem cell transplantation (HSCT) was performed with human leukocyte antigen (HLA)-matched donors. As revealed previously by Petersdorf et al., there are nine single nucleotide polymorphisms (SNPs) located in the HLA region that potentially modulate the efficacy of HSCT. In this study, we investigated whether or not the genomic variants 500 base pairs flanking the nine transplantation-related SNPs were related to the risk of post-HSCT relapse for patients with leukemia (n = 141). The genomic DNAs collected from 85 patients with acute myeloid leukemia (AML), 56 patients with acute lymphocytic leukemia (ALL), and their respective HLA-matched donors were subject to SNPs analysis, conferred by the mode of mismatch between donor-recipient pair or by recipient or donor genotype analysis. Seven SNPs were revealed to associate with the risk of relapse post-HSCT. For patients with AML, the increased risk of post-HSCT relapse was associated with the donor SNP of rs111394117 in the intron of NOTCH4 gene, and the recipient SNPs of rs213210 in the ring finger protein 1 (RING1) gene promoter, and rs17220087 and rs17213693 in the intron of HLA-DOB gene. For patients with ALL, the increased risk of post-HSCT relapse was associated with the donor SNP of rs213210 in the RING1 gene promoter, and the recipient SNPs of rs79327197 in the HLA-DOA gene promoter, rs2009658 in the telomeric end of lymphotoxin-alpha (LTA) gene, rs17220087 and rs17213693 in the intron of HLA-DOB gene, and rs2070120 in the 3′-UTR of HLA-DOB gene. This study sheds new insight into selecting better candidate donors for performing HSCT in patients with AML and ALL.

Mapping patterns of metastatic lymph nodes for postoperative radiotherapy in thoracic esophageal squamous cell carcinoma: a recommendation for clinical target volume definition

BackgroundThe clinical target volume (CTV) for postoperative radiotherapy for thoracic esophageal squamous cell carcinoma (TESCC) needs to be defined. The study aim was to map metastatic lymph nodes (LNMs) in a computed tomography (CT)-based atlas and delineate the postoperative radiotherapy target area.MethodsSixty-nine TESCC patients with first recurrent regional LNMs after esophagectomy were included. The LNM epicenters were registered onto corresponding anatomic axial CT images of a standard patient in the treatment position, with reference to the surrounding vascular and bony structures. The LNM sites were based on lymph node map of esophageal cancer, AJCC 8th. The lymph metastasis risk for different segments of thoracic esophagus was assessed.ResultsOne hundred and seventy-nine LNMs were mapped onto standard axial CT images. The upper-middle mediastinum region (station 1 to 8 M) contained 97% of metastases in the upper segment of thoracic esophagus, 90% in the middle segment, and 66% in the lower one. Advanced pathological stage (≥IIIB) might be a predictive factor for upper abdominal region (UAR) relapse in lower TESCC. Lower cervical para-tracheal LNMs were within a 4.3-cm bilaterally expanded area from the midline of the body and a 2.2-cm expanded area from the anterior of vertebral body, from the superior border of the C7, to the inferior border of the first thoracic vertebra.ConclusionA modified target from the upper border of C7 to the lower border of caudal margin of the inferior pulmonary vein level could cover the high-risk area of TESCC underwent postoperative radiotherapy. UAR seems to be an elective irradiation target for lower TESCC at pathological IIIB stage and higher.

Clinical results of intensity-modulated radiotherapy for 250 patients with cervical and upper thoracic esophageal carcinoma.

PurposeTo evaluate and analyze the efficacy and prognostic factors of intensity-modulated radiotherapy in 250 patients with cervical and upper esophageal carcinoma.Patients and methodsFrom September 2009 to September 2016, we retrospectively analyzed 250 patients with cervical and upper esophageal carcinoma treated with intensity-modulated radiotherapy (IMRT). In our study, all patients received IMRT, 54 patients with cervical esophageal carcinoma and 196 patients with upper esophageal carcinoma. Treatment response, survival status and failure modes of treatment were observed, and prognostic factors were analyzed.ResultsThe median survival time was 22.60 months and 3-year survival rate was 42%. The median progress-free survival time was 14.52 months and 3-year progress-free survival rate was 29.3%. The median survival time and the median progress-free survival time for cervical esophageal carcinoma were 20.40 and 15.15 months, respectively. The median survival time and the median progress-free survival time for upper esophageal carcinoma were 25.80 and 14.52 months, respectively (P>0.05). The significant clinical factors associated with survival were patient age, radiotherapy dose and T stages (P<0.05). Radiotherapy dose and concurrent chemoradiotherapy were the significant clinical factors related to progression-free survival (P<0.05). Recurrence appeared in 55.2% patients, including local recurrence in 22.40%, region relapse in 10.40% and distant metastasis in 12.40%. Local recurrence was the main mode of treatment failure. During treatment, the main treatment-related acute toxicity was leukocytopenia and anemia.ConclusionIn this study, IMRT demonstrated clinical benefit and well-tolerated toxicity in patients with cervical and upper esophageal carcinoma.

TTF-1 Expression is Correlated with Necessity of Postoperative Radiotherapy in Stage IIIA-N2 Lung Adenocarcinoma

The role of postoperative radiotherapy (PORT) in patient with stage IIIA-N2 non-small cell lung cancer is still controversial. It is urgent to explore the prognostic factor which might be helpful to make treatment choice. Thyroid transcription factor-1 (TTF-1) is overexpressed in up to 95% of primary lung adenocarcinoma. Several studies stated that TTF-1 is a prognostic factor in NSQ-NSCLC with conflicting results by reasons of different stages and treatments. Here, we conducted this study to gain a better insight into the association between TTF-1 expression and the necessity of postoperative radiotherapy in patients with stage IIIA-N2 lung adenocarcinoma after R0 resection. Patients with pathologically confirmed inoperable stage IIIA-N2 lung adenocarcinoma and underwent R0 resection with or without PORT in our institution were eligible. Data on demographics, histology, invasion, radiotherapy, chemotherapy, and survival were collected.TTF-1 expressions were determined by immunohistochemistry using available specimen after resection. Patients were classified into the TTF-1 overexpression group (TTF-1 : 3+) and TTF-1 not overexpression group (TTF-1 score 0-2+). Overall survival(OS), progression free survival(PFS), local regional relapse free survival(LRFS) and distant metastasis free survival(DMFS) were calculated from the date of resection. The necessity of PORT is assessed by log-rank test. From October 2006 to April 2015，101 patients fulfilled the enrollment criteria. Fifty-seven patients were male and 44 patients were female. The median age was 56 years old (34-74 years old). Negative, score 1+, score 2+ and score 3+ TTF-1 expression were in 8, 8,17, 68 patients, respectively. Median follow up time was 26.8 months. In patients with TTF-1 overexpression, 19 patients received PORT and 49 did not. For these patients, none of the OS(82.9% vs.81.8%,P=0.731), PFS(57.9% vs. 51.5%P=0.518), LRFS(100% vs.97.6%P=0.513) and DMFS(63.2% VS.62.4%P=0.910) were associated with PORT .In patients without TTF-1 expression, patients who received PORT got more favorable OS (50.0% vs.20.8%P=0.137)and PFS(83.3%VS.22.0%,p=0.028) compared with who did not. Moreover, there is no significant differences in LRFS (100% VS 86.5%p=0.395) and DMFS (66.7%vs 47.1%P=0.442) between patients with and without PORT. This retrospective study demonstrates that patients with TTF-1 score 0-2+ might benefit more from postoperative radiotherapy.