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K. Shibuya
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MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 15
- Moderators:K. Shibuya, Francoise Mornex
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 313 + 314
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MA 16.01 - Characterization of Autoantibody Responses in Thymoma with Myasthenia Gravis by Single-Cell Sequencing of B-cells (ID 8351)
15:45 - 15:50 | Presenting Author(s): Sukhmani Kaur Padda | Author(s): A. Gomez, J. Adamska, J. Preiss, N. Lingampalli, Heather A Wakelee, W. Robinson
- Abstract
- Presentation
Background:
Thymomas are frequently associated with paraneoplastic autoimmune syndromes, with the most common being Myasthenia Gravis (MG). MG is characterized by autoantibodies against muscle antigens, most frequently the acetylcholine receptor (AChR). Patients with thymoma also present with autoantibodies against striational muscle proteins (STR-Abs), such as the sarcomeric protein titin and the ryanodine receptor. These autoantibodies have been primarily regarded as diagnostic or prognostic markers, but little is known about their pathological mechanisms. Comprehensive mechanistic studies have been hindered by the lack of patient-derived monoclonal antibodies (mAbs). Such mAbs could help to define immunogenic epitopes in known or novel autoantigens, and would be useful for deciphering pathological mechanisms in vitro or in animal models.
Method:
We studied mAbs derived from a patient with thymoma and MG, with the patient’s written informed consent and under a Stanford IRB approved protocol. The patient had Masaoka-Koga stage II type B2 thymoma, with multiple recurrences over a period of 8 years. The patient’s MG symptoms included fatigable muscle weakness, the presence of anti-AChR antibodies, and high titer STR-Abs. The patient also had myositis with muscle-related symptoms worsening after thymectomy. We sequenced the repertoire of the patient’s plasmablasts, which are antibody-producing cells derived from the activated B-cell clones, using a barcode-based method for sequencing single-cell immunoglobulin genes developed in our lab. We then expressed 26 mAbs from clonally expanded families of antibodies from two different timepoints that are six months apart. The first timepoint was two years post-Rituximab, coinciding with a tumor recurrence and slow progression of muscle weakness. The second timepoint was a month after radiotherapy when the patient was admitted with severe muscle weakness and pain. Treatment included plasmapheresis/IVIG and Rituximab, with limited improvement over the weeks following hospitalization. The patient was on steroids at both timepoints. Anti-Titin serum antibody titers increased by 60% between these two timepoints.
Result:
Two of the mAbs that were expressed reacted with the main immunogenic region of titin in ELISA, and one of the clones was present at both of the timepoints investigated. These clones were detected despite B-cell depletion by treatment with Rituximab.
Conclusion:
Our results suggest that (i) sequencing single-cell immunoglobulins is a powerful technique for isolating and functionally characterizing mAbs against autoantigens in thymoma and that (ii) persisting or recurring autoreactive clones in patients with thymoma, such as anti-titin clones, may be associated with refractory paraneoplastic syndromes despite use of immunosuppressive therapies.
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MA 16.02 - Different Pattern and Prognostic Role of PD-L1, IDO, and Foxp3 Treg Expression in Thymoma and Thymic Carcinoma (ID 8796)
15:50 - 15:55 | Presenting Author(s): Yi-Ting Yen | Author(s): C. Chu, Yu-Feng Wei, Y. Cheng, Y. Tseng, W. Su, C. Lin
- Abstract
- Presentation
Background:
The immune checkpoint ligand programmed cell death 1 ligand (PD-L1) is expressed in various tumors, and the expression of indoleamine 2,3-dioxygenase (IDO) and Foxp3 Tregs are associated with tumor-induced tolerance and reported to be responsible for worse survival. Their prognostic role in thymoma and thymic carcinoma, however, has not been investigated.
Method:
A tissue microarray comprised of 100 surgically treated thymomas and 69 surgically treated thymic carcinomas was evaluated. PD-L1, IDO, and Foxp3 Treg staining was scored based on intensity as follows: 0 = none, 1 = equivocal/uninterpretable, 2 = weak, and 3 = intermediate-strong. The PD-L1, IDO, and Foxp3 Treg expression score was calculated using a semiquantitive method by multiplying the intensity [0-3] by the staining area [0-100%]. Those cases with all cores scoring three and 2 in more than 50% in the staining area were categorized as PD-L1, IDO, and Foxp3 Treg high expression and the remaining as low expression. Clinical information was also collected on age, sex, Masaoka staging, tumor histology, surgical radicality, and locoregional invasion. Statistical associations were evaluated using χ[2] test and Fisher’s exact test. Progression-free survival and overall survival curves were established by the Kaplan-Meier method and compared using a log-rank test.
Result:
Figure 1Figure 2Thirty-six (36%) thymoma and 25 (36%) thymic carcinoma cases revealed high expression of PD-L1. PD-L1 expression in thymoma is significantly associated with Masaoka staging (p<0.001), tumor histology (p<0.001). Although there was a trend toward worse progression-free and overall survival in thymoma and thymic carcinoma with high-expression of PD-L1, only the progression-free survival in thymoma was significantly worse (p=0.024). High expression of IDO was detected in 13 (13%) thymoma and 10 (14%) thymic carcinoma cases, whereas Foxp3 Treg was detected in 16 thymoma (16%) and 20 (29%) thymic carcinoma cases. The expressions of IDO and Foxp3 Treg were significantly associated with tumor histology in thymoma (p=0.002 and 0.016, respectively), but not in thymic carcinoma. Thymic carcinoma with high expression of IDO had a trend toward worse progression-free and overall survival trend (p=0.109 and 0.053, respectively). High expression of Foxp3 Treg, however, was significantly associated with better progression-free survival (p=0.006) and overall survival (p=0.007) in thymic carcinoma.
Conclusion:
This is the largest-scale study to evaluate PD-L1 expression in thymic epithelial tumors. Although high expression of PD-L1 might be associated with worse prognosis in thymoma and thymic carcinoma, further investigation into PD-L1, IDO, and Foxp3 Treg should be conducted to benefit anti-PD-L1 immunotherapy for thymic epithelial tumor.
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MA 16.03 - Health Utility Scores in Patients with Thymic Malignancies Treated with Multimodality Therapy (ID 9651)
15:55 - 16:00 | Presenting Author(s): Sara Victoria Soldera | Author(s): H. Naik, S. Shakik, M. Moskovitz, A. Parajian, N. Mittman, W. Xu, A.J. Hope, Andrea Bezjak, S. Keshavjee, G. Liu
- Abstract
- Presentation
Background:
The management of patients with locally advanced thymic malignancies remains controversial. Various combinations of surgical resection, chemotherapy and radiation are currently used. Given the generally favorable prognosis, treatment related toxicities and quality of life (QOL) could inform therapeutic options. For economic analyses, QOL can be measured as health utilities. This study describes health utility scores (HUS) in patients with locally advanced thymic malignancies, while determining the impact of multimodality regimens on HUS.
Method:
In a cross-sectional study (2014-2017), patients with Masaoka stage II-IVa thymic malignancies seen at a comprehensive cancer centre completed various self-reported questionnaires at routine medical visits. HUS as measured by the EuroQol-5-Dimensions (EQ-5D) with visual analogue scale (VAS) and self-reported Eastern Cooperative Oncology Group (ECOG) performance status were compared in patients treated with trimodality versus uni- or bimodality regimens. Patient-reported Edmonton Symptom Assessment Scale (ESAS) scores were also collected to explore symptom burden. Regression analysis was used to compare groups; multivariable analysis investigating potential confounders was also conducted.
Result:
From 2014 to 2017, 72 patients were included in the study; 43 (59.7%) were male with a median age of 58 years, 65 (90.3%) had thymoma while 7 (9.7%) had thymic carcinomas and median time since diagnosis was 50.5 months (range: 3-266). Compared to patients treated with uni/bimodality regimens (n=48), those treated with trimodality (n=24) had higher stage of disease at diagnosis and were more likely to have received multiple lines of chemotherapy. Median HUS and VAS did not differ between groups (trimodality vs uni/bimodality: HUS=0.77 vs 0.80, p=0.26; and VAS=80 vs 75, p=0.79, respectively). The distribution of patient-reported ECOG at assessment was also similar (p=1.00). ESAS scores for pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath were neither statistically nor clinically different by number of modalities of therapy. Subset analyses of individuals who were 1+ year since diagnosis affirmed these findings.
Conclusion:
Patients with stage II-IVa thymic malignancies report favorable HUS, VAS and self-reported ECOG with minimal symptom burden. Trimodality therapy appears similarly tolerable when compared to uni- and bimodality regimens in this population.
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MA 16.04 - Phase II Trial of S-1 Treatment as Palliative-Intent Chemotherapy for Previously Treated Advanced Thymic Carcinoma (ID 8627)
16:00 - 16:05 | Presenting Author(s): Fumiyoshi Ohyanagi | Author(s): Y. Okuma, Yasushi Goto, K. Sunami, Y. Nakahara, S. Kitazono, Y. Tambo, N. Yanagitani, Shintaro Kanda, A. Horiike, Hidehito Horinouchi, Y. Fujiwara, H. Nokihara, N. Yamamoto, Makoto Nishio, Yuichiro Ohe, Y. Hosomi
- Abstract
- Presentation
Background:
Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival with palliative-intent chemotherapy. Sunitinib and everolimus monotherapies have been proposed as active molecular-targeted approaches based on phase II (Ph II) trials, and S-1, an oral fluoropyrimidine, has been described in the NCCN guideline as an active cytotoxic agent for refractory TC based on a case series. Therefore, we conducted a Ph II trial to study the result of S-1 treatment in patients with refractory TC.
Method:
In this Ph II study performed at three cancer centers in Tokyo, we aimed to enroll 26 TC patients previously treated with platinum-based chemotherapy. The patients received S-1 orally twice daily at a dose of 40–60 mg/m2 for 4 weeks, followed by 2 weeks off until progressive disease or unacceptable toxicities. S-1 was used off-label. The primary end-point was determining the objective response rate, and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicities.
Result:
Twenty-six patients (10 males) were recruited between November 2013 and May 2016. The median age was 63 (27–74) years. Among the 26 patients, 23 had squamous cell carcinoma histology and 10 had an ECOG performance status of 0. Additionally, one patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (95% confidence interval [CI], 16.5–50.0) and a 65.4% disease control rate (95% CI, 46.2–80.6). After a median follow-up of 13.4 months, the median PFS was 4.3 months (95% CI, 2.3–7.6 months) and median OS was 23.4 months (95% CI, 12.8–not reached). Treatment-related adverse events (AEs) of grade ≥3 included neutropenia (12%), skin rash (8%), elevated ALT, decreased WBC count, and fatigue (4%). No treatment-related death was observed. However, treatment was discontinued in three patients (12%) because of AEs.
Conclusion:
S-1 for refractory TC confirmed clinical activity with good tolerability. Clinical trial identification: UMIN000010736
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MA 16.05 - Discussant - MA 16.01, MA 16.02, MA 16.03, MA 16.04 (ID 10854)
16:05 - 16:20 | Presenting Author(s): Mir Alireza Hoda
- Abstract
- Presentation
Abstract not provided
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MA 16.06 - Minimally Invasive Thoracoscopic Thymectomy for Early-Stage Thymomas: Modified Subxiphoid Approach Versus Unilateral Approach (ID 10081)
16:20 - 16:25 | Presenting Author(s): Jian-Yong Ding | Author(s): H. Wang
- Abstract
- Presentation
Background:
Conventionally, minimally invasive thymectomy for early-stage thymoma was performed via unilateral thoracoscopic approach. However it is sometimes criticized for bad exposure of anterior mediastinum which may be disadvantagous for the surgery. Recently, we attempted a modified subxiphoid thoracoscopic approach with novel sternal-elevating technique to reach better surgical exposure and less trauma.
Method:
From January 2015 to December 2016, a total of 83 consecutive patients with early-stage thymomas without myasthenia gravis were enrolled. Between them, 36 patients were performed thoracoscopic thymectomy via subxiphoid approach (Group S) . Three subxiphoid incisions (12mm*1, 5mm*2) with the aid of artificial CO~2~ pneumothorax (8cmH~2~O) were used. Additionally, we used the sternum-elevating device (Rul-tractor, USA) through the 3rd intercostal incision (5mm*1) beside the sternum. And the other 47 cases underwent conventional thymectomy via unilateral 3-port thoracoscopic approach (Group UL). The perioperative outcome of two groups were compared.
Result:
The two groups were comparable on patients[,] demographics. Conversion to open surgery occurred in 1 case (due to bleeding) in Group UL. Compared with Group UL, the patients in Group S had much shorter surgical duration [(63.5±10.7)min vs (87.7±13.1)min, p=0.000], much less pain scores (2.3±1.0 vs 3.1±1.30, p=0.002) and earlier pleural drainage removal [(1.6±0.6)d vs (2.3±0.9)d, p=0.000]. The complications were similar (5.6% vs 6.4%, p=0.758). No significant difference was found on the other outcomes between the two groups, including blood loss and postoperative hospital stay.
Conclusion:
This study suggests that the modified subxiphoid thoracoscopic approach seems to be more effective for thymectomy for early-stage thymomas. This novel approach could improve surgical exposure, accelerate the operative progress and result in less trauma and pain. It could be a promising refinement for future thymic surgery.
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MA 16.07 - Appropriate Time to Adjuvant Radiotherapy for Thymoma with MG after Extended Thymectomy (ID 8307)
16:25 - 16:30 | Presenting Author(s): Lei Yu
- Abstract
- Presentation
Background:
The co-existence of MG and thymoma makes the surgical treatment more complicated and adjuvant radiation more controversial. The aim of this article is to investigate whether patients with MG and thymoma should receive mediastinal radiation therapy and when after extended thymectomy.
Method:
Between 2003 and 2014, 181 patients with MG and thymoma underwent extended thymectomy. According to application of radiation therapy, these patients were divided into 2 groups: Group 1 (n=157), patients having mediastinal radiation therapy after surgery; Group 2, without adjuvant radiation therapy (n = 24). Group 1 was subdivided into 3 subgroups: 1-month subgroup(n = 98); 2-month subgroup(n = 7): and 3-month subgroup(n = 52).
Result:
There were no intraoperative deaths and no inoperable cases. 172 patients underwent extended thymectomy by video-assisted thoracoscopic surgery, and 9 undergoing the trans-sternal approach due to thymoma invading great vessels. There was no significant difference in the aspects, such as length of surgery, Operative complications, and ICU stay, between 1-month subgroup, 3-month subgroup and Group 2. The proportions of type A, AB, B1, B2, B3, and thymic carcinoma were 0.6%, 18.2%, 26.5%, 33.7%,21.0%, and 0%, respectively. There were no radiation-related deaths. 159 patients were followed for 15 months to 12 years. Postoperative myasthenic crisis occurred in 40 cases. There was a significant difference in occurrence of postoperative myasthenic crisis between 1-month subgroup and Group 2 (P=0.031). The rates of reaching CSR were 32.6% in 1-month subgroup, 25% in 3-month subgroup, and 22.7% in Group 2, respectively. Overall survival rates of 1-month subgroup, 3-month subgroup, and Group 2 were 88.8%, 83.3%, and 77.3%, respectively. Among 14 recurrences, 11 cases happened in pleural cavity; 2 recurrences in lung; and one patient having metastasis to liver. There was no lymph node metastasis detected. Kaplan-Meier survival curves demonstrate that within 7 years after surgery, there is no significant difference in aspects of overall survival and disease-free survival between 1-month subgroup, 3-month subgroup and Group 2; over 8 years after surgery, disease-free survival rates in 1-month subgroup, 3-month subgroup and Group 2 were 79.4%, 70.6% and 55.3%, respectively.
Conclusion:
Adjuvant radiation within one month after extended thymectomy may be helpful in controlling postoperative MG, such as decreasing possibility of postoperative myasthenic crisis, and raising cumulative probabilities of reaching CSR. Whether it might have influence in prognosis of thymoma with MG needs to be further investigated in the future. In recurrences of thymoma patients with MG, no lymph node metastasis was detected
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MA 16.08 - Surgery for Pleural Dissemination of Thymoma; A 20-Year Experience (ID 9191)
16:30 - 16:35 | Presenting Author(s): Kenji Kimura | Author(s): Ryu Kanzaki, N. Ose, T. Kawamura, S. Funaki, Yasushi Shintani, M. Minami, Meinoshin Okumura
- Abstract
- Presentation
Background:
Surgical management of pleural dissemination of thymoma has been recommended in some reports, while reports on the long- term results of pleural dissemination resection are few. The aim of this study was to assess mid- and long- term results of surgical resection of pleural dissemination of thymoma.
Method:
We retrospectively analyzed data from patients with synchronous or metachronous pleural dissemination and primary thymoma who underwent surgical resection between 1996 and 2016 in our hospital.
Result:
During the study period, 38 patients underwent resection of pleural dissemination of thymoma. The synchronous group consisted of 21 patients with a median age of 50.2 years (range: 28—75 years) at the time of resection. The metachronous group consisted of 17 patients with a median age of 46.7 years (range: 30—65 years) at the time of resection of pleural dissemination. The median follow-up was 72.7 months (range: 3—248 months). In the synchronous group, 19 patients were in stage IVa and 2 patients were in stage IVb. The histological type of thymoma was type B1 in 3 patients, type B2 in 9 patients, typeB3 in 9 patients. In the metachronous group, Masaoka stage of the primary thymoma was as follows; 3 patients were in stage I, 5 patients were in stage II, 7 patients were in stage III and 2 patients were in stage IVb. The histological types of the resected dissemination nodule were type AB in 1 patient, type B1 in 1 patient, type B2 in 5 patients, and typeB3 in 10 patients. A macroscopic complete resection of pleural dissemination was achieved in 30 patients (79%) of all the patients. No perioperative deaths occured. Postoperative complications occurred in 5 patients (13.2%). During the observation period, 5 patients died (relation to the tumor in 4) in the synchronous group and 1 patient died (unrelated to the tumor) in the metachronous group. The 5- and 10-year overall survival rates of all the patients were 87.6% and 69.2%, respectively. Of all the patients, 14 received repeated resection of the pleural disseminated nodule. The 5- and 10-year overall survival rates from the first resection of pleural dissemination were 76.6% and 46.0% in the non-repeat resection group and 100% and 88.9% in the repeat resection group, respectively.
Conclusion:
Surgery for pleural dissemination of thymoma was safely performed and provides favorable prognosis. Repeat resection for pleural dissemination could be effective in achieving a prolonged survival.
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MA 16.09 - Discussant - MA 16.06, MA 16.07, MA 16.08 (ID 10855)
16:35 - 16:50 | Presenting Author(s): Takashi Ohtsuka
- Abstract
- Presentation
Abstract not provided
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MA 16.10 - Treatment Outcomes of Primary Malignant Germ Cell Tumors of the Mediastinum (ID 8753)
16:50 - 16:55 | Presenting Author(s): Tadashi Sakane | Author(s): Satoru Moriyama, H. Haneda, Katsuhiro Okuda, O. Kawano, T. Watanabe, R. Oda, R. Nakanishi
- Abstract
- Presentation
Background:
Primary mediastinal malignant germ cell tumors (GCT) are rare neoplasms with various histopathological findings and contain complicated clinical characteristics. Chemotherapy plays an important role in the treatment and there are some cases where a good prognosis is expected with multimodal treatment including surgical resection, pre- and postoperative chemoradiotherapy.
Method:
The medical records of 27 patients who were treated in our institution between 1988 and 2014 were retrospectively reviewed. We investigated the clinical characteristics and the outcomes of treatment.
Result:
All patients were male with a mean age of 30.7 years (range, 16-53 years), including 17 cases of seminoma (SGCT group) and 10 cases of non-seminoma (NSGCT group). Twenty-three patients underwent surgery and the remaining four patients received chemotherapy and/or radiotherapy without surgery. Of the 23 patients who underwent surgery, 17 cases received preoperative chemotherapy and 15 cases were treated with postoperative chemo/radiotherapy. In six patients, surgery was performed without preoperative chemotherapy due to the suspicious of thymoma, and was followed by postoperative chemo/radiotherapy. Among 24 patients whose serum tumor marker levels were measured before the treatment, 15 patients showed elevated serum tumor marker levels [five (35.7%) in SGCT group and 10 (100.0%) in NSGCT group]. Furthermore, among 20 patients whose serum tumor marker levels were measured before surgery, four patients showed elevated serum tumor marker levels [one (9.1%) in SGCT group and three (33.3%) in NSGCT group]. The median follow-up period after the treatment was 68 months (range, 4-316 months). The 5-year and 10-year survival rate was 88% and 88% in SGCT group, respectively, and 60% and 45% in NSGCT group, respectively (p=0.031). Although there was no relationship between the serum tumor marker levels before the treatment and the prognosis, the patients without elevated tumor marker levels revealed better prognosis than those with elevated one (p=0.014).
Conclusion:
The treatment for mediastinal malignant GCT in our institution was feasible with favorable outcomes. Although malignant GCT has poor prognosis especially in NSGCT group, chemotherapy which normalizes serum tumor marker levels can improve its prognosis.
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- Abstract
- Presentation
Background:
Adenoid cystic carcinoma (ACC) of the trachea represents less than 1% of all respiratory tract cancers and lacks well-characterized molecular markers. There is no standard of care treatment for patients with recurrent and/or metastatic disease. The aim of this study is to identify and characterize novel, activating mutations in Notch receptors in ACC of the trachea and to determine response to Notch inhibitor Brontictuzumab.
Method:
Patients with ACC of the trachea at four institutions from 2011 through 2016 were identified. Target exome sequencing or analysis of hotspot mutations in cancer-related genes was performed by next-generation sequencing. Luciferase reporter assays were performed to confirm target gene expression in vitro. Patient-derived xenograft (PDX) models were sequenced, and Notch-mutant models were treated with Brontictuzumab. Gene-expression and functional analyses were performed to study the mechanism of activation through mutation and inhibition by Brontictuzumab.
Result:
We showed that gain-of-function mutations of the Notch-1 gene in the PEST domain occurred in 10/62 tumors, leading to stabilization of the intracellular cleaved formed of Notch-1 (ICN1). Notch-1 mutations were associated with increased Notch-1 activation and its target gene HES-1. Mutations in Notch-2 (3/62), Notch-4 (3/62), Jagged-1 (2/62), FBXW-7 (4/62), and SPEN (1/62) were also identified in 13 (21.0%) patients. We observed a strong inverse correlation of mRNA levels between FBXW-7 and HES-1. Notch-1 mutations were associated with solid subtype (P = 0.02), advanced stage at diagnosis (P = 0.01), metastasis (P = 0.002), shorter relapse-free survival (RFS) (P = 0.008) and shorter overall survival (OS) (P = 0.006) compared with Notch-1 wild-type tumors. Notch-1 mutations were not an independent prognostic factor in the presence of histologic subtype and tumor stage. We demonstrated that Notch inhibition by Brontictuzumab reduced tumor cell proliferation and tumor formation in ACC patient-derived xenograft model harboring Notch-1 mutation.
Conclusion:
These data suggest that activated Notch pathway may be important to pathogenesis of ACC of the trachea and reveal Notch-1 as a target for therapeutic intervention in this subset of patients.
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MA 16.12 - Prolonged Survival after Pulmonary Metastasectomy for Testicular Germ-cell Tumors in a Single Institution (ID 10183)
17:00 - 17:05 | Presenting Author(s): Jose Francisco Corona-Cruz | Author(s): G. Mirando-Devora, J.A. González Luna, M.A. Alvarez-Avitia, J. Martinez-Cedillo, R.A. López Saucedo, Oscar Arrieta
- Abstract
- Presentation
Background:
Testicular Germ-cell tumors are a common cancer in adults younger than 30 years-old. Extensive dissemination and high senitivity to chemotherapy are their principal characteristics. Chemotherapy is the standard of care, with an 80% probability of complete biochemical response with first line chemotherapy. Surgical resection of residual lesions after chemotherapy is indicated in some cases to rule out the presence of mature teratoma or viable tumor.
Method:
Retrospective chart review of patients with metastastic testicular Germ-cell tumors treated with chemotherapy and pulmonary metastasectomy from January 2006 to December 2014.
Result:
We found 56 cases with complete data for revision. Mean age was 25 years (16-48) Patients with lung metastases at diagnosis were 83.9%. All patients were treated with chemotherapy after initial orchiectomy. Preoperative serum tumor markers were negative in 44 patients (78%) Thoracotomy was performed in 48 cases (85.7%) and minimally invasive surgery in 8 cases (14.3%) Pulmonary wedge resection was performed in 52 patients (92.8%) and a lobectomy was required in 4 patients (7.2%) A R0 resection was achieved in 98.3%. Necrosis was reported in 25 cases (44.6%), mature teratoma in 17 (30.4%), viable germ-cell tumor in 13 patients (23.2%) and 1 case with seminoma (1.8%) All patients with viable tumor were offered postoperative chemotherapy. Median follow-up was 53.2 months (6-110). Median Overall Survival has not reached. Factors associated with improved survival were negative preoperative serum tumor markers and abscense of viable germ-cell tumor on resected specimens. Figure 1
Conclusion:
Removal of residual lesions after chemotherapy serves a double purpose, as an adjuvant treatment to chemotherapy allowing for “local” control of metastases and it also provides information about response to chemotherapy, with implications on prognosis and guiding postoperative treatment. In our cohort we demonstrate that despite a high proportion of viable tumors on surgical specimen, multi-modality treatment including lung metastasectomy is associated with prolonged survival
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- Abstract
- Presentation
Background:
Programmed death-ligand 1 (PD-L1), is reported to serve as an indicator of prognosis in many malignant tumors. The aim of this study was to determine whether PD-L1 expression status in tumor cell can predict patient’s prognosis in esophageal squamous cell carcinoma (ESCC).
Method:
246 paraffin-embedded tissue samples were detected PD-L1 expression by immunohistochemistry from ESCC patients after surgery. And we statistically analyzed the association between expression of PD-L1 and clinicopathological factors and outcomes of survival.
Result:
The rate of positive PD-L1 expression was 24.4% (60/246) . Multivariate analysis indicated positive PD-L1 expression was associated with advanced TNM stage (P=0.009). The median of overall survival (OS) for patients with positive PD-L1 expression was similar to those with negative PD-L1 expression (Median OS, 52.4 vs. 56.4 months, P=0.466). However, in the subgroup analysis, the results indicated that the prognosis of patients with positive PD-L1 expression treated with adjuvant radiotherapy was significantly better than those with negative PD-L1 expression (Median OS, 84.4 vs. 36.0 months, P=0.046), while the OS of positive PD-L1 expression patients treated with adjuvant chemotherapy was poorer than those with negative PD-L1 expression although without significant statistical differences (Median OS, 21.8 months vs. 41.0 months, P=0.765) (Figure 1). Multivariate Cox regression hazards analysis revealed PD-L1 expression statue was not an independent prognostic factor (P=0.804) for entire cohort.Figure 1 Subgroup analysis for OS in ESCC based upon PD-L1 expression. (A) Subgroup of surgery alone; (B) Subgroup of surgery plus adjuvant chemotherapy; (C) Subgroup of surgery plus adjuvant radiotherapy; (D) Subgroup of surgery plus adjuvant chemoradiotherapy.
Conclusion:
Positive PD-L1 expression was likely to be more associated with malignant biological behavior of ESCC. PD-L1 expression was not a prognostic factor of OS for entire cohort, however, it is a prognostic factor in patients treated with postoperative adjuvant radiotherapy.
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- Abstract
- Presentation
Background:
c-Met is reported to serve as a poor prognostic factor in many malignant tumors. Previous studies have suggested the involvement of c-Met in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients.
Method:
The expression of c-Met was immunohistochemically assessed in 180 surgically obtained tissue specimens. The correlation between c-Met expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with c-Met inhibitor in ESCC cell line.
Result:
There was no significantly correlated between c-Met expression and patients’ clinicopathological features. However, there was a significant difference in OS (median: 41.9 vs. 56.7 months; p= 0.001) between the high c-Met and low/negative c-Met expressing groups. In subgroup of patients with adjuvant radiotherapy, high expression of c-Met was correlated with poor disease prognosis (p= 0.002), while there was no significant correlation in patients with adjuvant chemotherapy. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor significantly inhibited the growth of an ESCC cell line with high c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor.
Conclusion:
The results of our study identified c-Met expression as an independent prognostic factor in ESCC and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with high c-Met expression.
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MA 16.15 - Discussant - MA 16.10, MA 16.11, MA 16.12, MA 16.13, MA 16.14 (ID 10856)
17:15 - 17:30 | Presenting Author(s): Chang Hyun Kang
- Abstract
- Presentation
Abstract not provided
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