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Shinichi Toyooka



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-18 - Clinical Features of Locally Advanced Lung Cancer Patients with Radiation Pneumonitis After Induction Chemoradiotherapy (Now Available) (ID 2199)

      08:00 - 18:00  |  Author(s): Shinichi Toyooka

      • Abstract
      • Slides

      Background

      The therapeutic management of locally advanced non-small cell lung cancer (NSCLC), such as those in the N2-3, bulky N1, or T3-4 stage, remains controversial. Induction chemoradiotherapy (CRT) followed by surgery is one of the potential therapeutic options for locally advanced NSCLC, however, sometimes develops radiation pneumonitis (RP). Severe RP induce remarkable respiratory disfunction, resulting in a delay of next treatment. The purpose of this study is to reveal the clinical features of NSCLC patients with RP after induction CRT.

      Method

      The clinical data of NSCLC patients who underwent surgical resection of lung cancer after induction CRT between 1999 to 2017 at our institution were analyzed. We compared NSCLC patients who had RP with those who didn’t, regarding patient’s and therapeutic factors, and their prognosis. RP of our cases was defined as RP which occurred between the administration of induction CRT and 30 days after surgery.

      Result

      A total of 172 data of NSCLC patients who underwent surgical resection of NSCLC of stage IIB–IIIC after induction CRT was collected. Among them, 34 NSCLC patients had RP, and 15 NSCLC patients received steroid therapy in 30 NSCLC patients, able to be assessed retrospectively. Non-smoking status was significantly associated with RP in univariate analysis (p = 0.006) and in multivariate analysis (odds ratio: 3.70, 95% confidence interval: 1.05-13.10, p = 0.042). Duration between completion of RT and surgery was longer in NSCLC patients with RP than those without RP (range [median]: 14-141 [45.5] vs 23-91 [40.0], p = 0.029). Adjuvant therapy was more frequently given to the patients without RP (p = 0.019). No significant difference in overall survival (OS) was observed between the 2 groups.

      Conclusion

      Non-smoking status was the risk factor of RP of NSCLC patients who received induction CRT followed by surgery. The frequency of adjuvant therapy was more in NSCLC patients without RP than those with RP while OS was not different in the 2 groups.

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    EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.16-41 - Lung Lobectomy for Elderly Patients Over 85 Years Old Is a Risk of a Complication and Long-Term Hospitalization Compared with Sublobar Resection (Now Available) (ID 1360)

      08:00 - 18:00  |  Author(s): Shinichi Toyooka

      • Abstract
      • Slides

      Background

      The increased number of elderly patients with non-small lung cancer underwent lung resection, though the clinical outcome has remained unclear. In this study, we reviewed the postoperative complications and clinical outcome after lung resection in elderly patients over 85 years old with lung cancer, defied as “very elderly patients”.

      Method

      Among patients who underwent lung surgery for non-small cell lung cancer (NSCLC from 2012 to 2019 in our institute, a total 24 patients were enrolled for this retrospective study.

      Result

      During the study period, 24 elderly patients (mean age, 87.3) underwent lung resection, consisting of 14 female and 11 male, 19 adenocarcinomas and 5 non-adenocarcinomas, and 19 c-Stage 0: 1, IA: 16, IB: 3, IIA: 2, IIB: 1, IIIA:1[KS1] (based on UICC 7th edition), and 12 sublobar surgery (6 wedge resections and 6 segmentectomies) and 12 lobectomy. Perioperative complications were observed in 8 patients, and the average hospitalization days are 23.4 days. Next, patients were Stratified by the surgical procedure . The clinical stage is, in limited resection group,cStage 0: 1, 1A: 8, 1B: 3, otherwise in lobectomy group, cStage1A: 8, 1B: 0, 2A: 2, 2B: 1, 3A:1[KS2] . The procedures underwent complete video assisted thoracic surgery are 6 in sublobar resection, 3 in lobectomy. Average operation time is 168 minutes in limited resection, 207 minutes in lobectomy, and blood loss is 48.8 ml and 67.5 ml, respectively. No perioperative mortality was observed within 30 days after surgery. There are more complications in lobectomy group than in limited resection group (50.0%, 25.0%), although the p value was not significant ( p = 0.22). [KS3] The patients need HOT after surgery is one in limited resection, two in lobectomy. Especially the frequency of onset of arrhythmia requiring treatment is high, 33.3%, in lobectomy group and one case needs implanting a pacemaker. On the other a patient in lobectomy group onsets appendicitis after thoracic surgery and the patient is proceeded appendectomy. The average hospitalization days in lobectomy group, 32.5 days, are longer than in limited resection group, 14.3 days.( p = 0.20)

      Conclusion

      Lung lobectomy in very elderly patients is associated with postoperative complications and prolonged hospitalization compared with sublobar surgery.

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    EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.18-08 - Pulmonary Lobectomy and Completion Pneumonectomy for Ipsilateral Lung Cancer After Radical Resection (Now Available) (ID 1218)

      08:00 - 18:00  |  Author(s): Shinichi Toyooka

      • Abstract
      • Slides

      Background

      Ipsilateral reoperation such as lobectomy and completion pneumonectomy after radical resection of lung cancer is a high-risk operation. We evaluated outcomes after these operations in our hospital.

      Method

      We retrospectively reviewed the records of 27 patients who underwent ipsilateral lobectomy or completion lobectomy for new primary lung cancer or recurrence after pulmonary lobectomy or bi-lobectomy between 1998 and 2017.

      Result

      9 patients underwent completion lobectomy, of which 4 were right and 5 were left, and 18 patients underwent lobectomy. Mean operative time was 308.7±27.4 minutes, and mean blood loss was 706.9±254.3mL. Blood loss was significantly higher in completion pneumonectomy patients as compared to lobectomy patients, whereas operative time was not different between the operations. There was no perioperative mortality, but intraoperative complications were seen in 4 cases (14.8%), which were 2 pulmonary artery injury, superior venous cava injury and azygos vein injury. Perioperative morbidity was seen in 8 cases (29.6%), and postoperative bronchopleural fistula occurred in one case. Fourteen patients had Pathological stage IA disease, 6 had IB, and 5 stage II or over. As clinical outcome, 5-year overall survival rate was 71.1%.

      Conclusion

      Pulmonary lobectomy or completion pneumonectomy for ipsilateral lung cancer after radical resection were performed in 27 patients without perioperative mortality. Our results strongly suggests that this strategy is a meaningful option for new or recurrent ipsilateral lung cancer.

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    MA20 - Thymic Tumors: From Molecular to Clinical Results and New Challenges in Other Rare Thoracic Tumors (ID 149)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
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      MA20.11 - Surgical Treatment for Metastatic Lung Tumors from Sarcomas of Soft Tissue and Bone (Now Available) (ID 2391)

      11:30 - 13:00  |  Author(s): Shinichi Toyooka

      • Abstract
      • Presentation
      • Slides

      Background

      Sarcoma is one of the refractory malignant tumors and often develops pulmonary metastasis. The purpose of this study was to evaluate the impact of surgical resection for metastatic lung tumors from sarcomas of soft tissue and bone retrospectively.

      Method

      Between 2006 and 2015, we had a total of 158 patients with metastatic lung tumors from soft-tissue and bone sarcomas who underwent pulmonary metastasectomy for the first time. In total, 265 surgical procedures were performed in Okayama University Hospital in this period. We analyzed the age, sex, site of primary lesion, histology, extent of primary tumors at the initial diagnosis, extent of pulmonary metastases at the first pulmonary metastasectomy, presence or absence of local recurrence and/or extrapulmonary metastases with or before pulmonary metastases, operative procedures, size of the largest lesions resected, maximum number of the resected tumors, postoperative complications, and the prognosis at the end of 2018.

      Result

      Average number of resected tumors per intervention was 4.0 (range 1-19). These sarcoma patients consisted of 36 males and 122 females, and their average age was 53.7 years (range 14-88 years). Leiomyosarcoma was the most common histological subtype (n = 92, 58.2%) and uterus was the most common location of the primary disease (n = 71, 44.9%). Operative procedures were composed of 202 partial resections, 35 segmentectomies with or without partial resections, 26 lobectomies with or without partial resections, 1 pneumonectomy, and 1 basal segmental auto-transplantation after pneumonectomy. The postoperative complications were limited, showing that pulmonary metastasectomies for sarcomas are acceptable. Overall 3-year survival after the first pulmonary metastasectomy was 50.6%. In univariate analysis, the survival was significantly better for the group with disease-free interval of more than 2 years from the date of the initial treatment for primary disease until the date of diagnosis for the first pulmonary metastasis, the one who underwent pulmonary resections three times or more, and the one in which size of the largest resected lesion was 20 mm or less. Those factors significant in univariate analysis were all significant in multivariate analysis.

      Conclusion

      Surgical resections for metastatic lung tumors from sarcomas of soft tissue and bone were performed without major complications, indicating the acceptable feasibility. If disease-free interval is more than 2 years and the size of the largest resected lesion is less than 20 mm, patients may maximally benefit from pulmonary resection. In order to increase the opportunities of pulmonary resections, we should preserve the lung parenchyma as much as possible when performing pulmonary metatstasectomy, resulting in the better survival.

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    P1.03 - Biology (ID 161)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.03-16 - Anti-Tumor Effect of Pan-RAF Inhibitor in NSCLC Cells Harboring BRAF Mutation (Now Available) (ID 1206)

      09:45 - 18:00  |  Author(s): Shinichi Toyooka

      • Abstract
      • Slides

      Background

      BRAF mutation occurs in 0.5-3% of lung adenocarcinoma and acts as an oncogenic driver. Dabrafenib (BRAF inhibitor) combined with trametinib (MEK inhibitor) has shown substantial antitumor effect in patients with non-small-cell lung cancer (NSCLC) harboring BRAF V600E mutation. However, in patients with NSCLC harboring BRAF non-V600E mutation, there are few reports of effective targeted therapy. LY3009120, a newly discovered pan-RAF inhibitor, showed strong anti-tumor effect in BRAF-mutant cancers, such as melanoma, colorectal and pancreatic cancers in preclinical studies. In this study, we evaluated the anti-tumor effect of LY3009120 in BRAF-mutant NSCLC cells.

      Method

      We examined the sensitivity of LY3009120 against normal bronchial cells BEAS-2B which ectopically overexpressing wild-type or mutant BRAF. Human cDNAs encoding full-length BRAF (wild-type and its variants V600E and G469V) were inserted into the pIDT-SMART (C-TSC) vector, pCMViRTSC. In addition, we treated four BRAF-mutant NSCLC cell lines, one BRAF-mutant colorectal cancer cell line, and one KRAS-mutant cell line with LY3009120. The type of BRAF mutation consisted of V600E, L597V, G469A, and G466V. We determined cell proliferation by MTS assay and calculated the IC50 values. We also performed Western blotting to investigate downstream signaling pathways.

      Result

      BEAS-2B cells ectopically overexpressing wild-type BRAF or mutants (V600E and G469V) showed constitutive auto phosphorylation of BRAF and activation of downstream signaling by Western blotting. The IC50 values in BRAF mutant cell lines ranged from 9.4nM to 1,193nM, which suggests strong anti-tumor effect of LY3009120. This effect was observed regardless of the type of BRAF mutation, including non-V600E mutation. On the other hand, LY3009120 did not show anti-tumor effect in KRAS-mutant cell (IC50 value, 6,948nM). LY3009120 suppressed the phosphorylation of downstream MEK and ERK activation in BRAF-mutant cell lines by Western blotting.

      Conclusion

      LY3009120 showed strong anti-tumor effect in NSCLC cells harboring BRAF mutation regardless of the type of mutation, suggesting that LY3009120 can be a promising therapeutic option in the treatment of NSCLC harboring BRAF mutation.

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    P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.16-35 - The Prognostic Impact of Sarcopenia on the Clinical Outcome of Thoracic Surgery for Non-Small Cell Lung Cancer in Elderly Patients (ID 1544)

      09:45 - 18:00  |  Author(s): Shinichi Toyooka

      • Abstract
      • Slides

      Background

      The elderly patients who undergo surgery for non-small cell lung cancer (NSCLC) is increasing in Japan whereas they are at high risk for surgery because of weakness of physical strength and increased comorbidity. Skeltal muscle depletion, referred to as sarcopenia, has recently been identified as a risk factor of poor clinical outcomes after surgery in the patients with various malignancies including NSCLC. We investigated the impact of sarcopenia on the clinical outcome of thoracic surgery for NSCLC in elderly patients.

      Method

      We enrolled 259 patients over 65 years old with NSCLC who underwent pulmonary resection (lobectomy or segmentectomy) without any induction treatment before surgery in our hospital during 2012 to 2015. Sarcopenia was assessed by the psoas muscle mass index (PMI, cm2/m2) using the computed tomography imaging at the third lumbar vertebra level before surgery. Postoperative complications, which were observed within 30days after surgery, were classified according to Clavien-Dindo classification. Overall survival (OS) was evaluated by the Kaplan-Meier method with log-rank test (univariate analyses) and by the cox proportional hazard model (multivariate analyses).

      Result

      Median age was 73 years old (65 - 92). One hundred fifty-five (60%) patients were male. Two hundred nine (81%) patients were cStage0 or I. Fifty-seven (22%) patients were squamous cell carcinoma (SCC). Postoperative pneumonia, arrhythmia, and delirium were observed in 17 (7%), 35 (14%) and 17 (7%) patients, respectively. Median follow-up was 48.7 months (range 3.0 – 79.6). Using the cutoff values as previously reported, 179 (69%) and 80 (31%) patients were diagnosed as sarcopenic and non-sarcopenic, respectively. Male and ever smoker were significantly more frequent in the sarcopenic patients than the non-sarcopenic patients (P < 0.001 and P = 0.018, respectively). The sarcopenic patients showed the trend of high incidence of Postoperative complications, however, there was no significant difference in OS between the sarcopenic and non-sarcopenic patients. Next, we performed the subgroup analysis to elucidate the prognostic factors only in the elderly sarcopenic patients. Among 179 sarcopenic patients, multivariate analysis including statistically significant factors in the univariate analysis revealed that the patients with restrictive lung disease, advanced cStage, postoperative pneumonia and delirium were inferior in OS [Hazard Ratio, 11.1, 3.6, 5.3 and 4.6; 95% confidence interval, 1.6 to 68.1, 1.1 to 13.0, 1.4 to 20.0 and 1.1 to 16.5; P= 0.011, 0.037, 0.017 and 0.041], suggesting the importance of the intensive perioperative management to avoid complications.

      Conclusion

      Perioperative complications are significantly associated with the prognosis of the sarcopenic elderly patients with NSCLC. Intensive perioperative management is mandatory for NSCLC patients with sarcopenia to improve the clinical outcome after thoracic surgery.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-82 - Lung Cancer in Lung Transplant Recipients (Now Available) (ID 2334)

      10:15 - 18:15  |  Author(s): Shinichi Toyooka

      • Abstract
      • Slides

      Background

      Long-term immunosuppression is considered to increase the chance of developing malignancy, which is one of the leading causes of death after organ transplantation. Lung cancer in lung transplant recipients can originate from de-novo occurrence, transplanted donor’s lung and progression/recurrence of the recipient’s lung cancer. We conducted a survey of lung cancer in lung transplant recipients in our institution and report the case series.

      Method

      All 189 recipients who underwent lung transplantation (97 brain-dead donor lung transplantation, 90 living donor lobar lung transplantation, 2 hybrid lung transplantation) since October 1998 until December 2018 at Okayama University Hospital were retrospectively reviewed.

      Result

      Lung cancer was diagnosed in 4/189 (2.1%) of 16/189 (8.5%) all malignant diseases, in lung transplant recipients with a median follow-up of 4.5 years. Whereas de novo lung cancer occurred in one patient, patient-baring lung cancer was histologically detected in resected lung in three patients, leading to progression after transplantation in the two recipients. One recipient who had a previous history of lung cancer with over 5-year disease free period, experienced no recurrence afterword. All three recipients who had advanced lung cancer died relatively early from the diagnosis of lung cancer, regardless of cancer treatment.

      Lung cancer in lung transplant recipients could be difficult to detect by radiological screening and biopsy due to severely deteriorated lung condition, especially in idiopathic interstitial pneumonitis. Additionally, recipients with advanced lung cancer seem to have poor prognosis.

      Case Underlying disease Occurrence LTx - Lung cancer Degree of progression Treatment/Prognosis
      #1 LAM De novo 10 years Chest wall invasion Right pneumonectomy (10 months)chemotherapy (9 months)death
      #2 IIP Resected recipient’s lung 15 months Mediastinal lymph-nodes Lymph-node resection (10 months) death
      #3 IIP Resected recipient’s lung 3 months Pleural Dissemination chemotherapy (6 months)death
      #4 BO Resected recipient’s lung nil nil

      nil

      LAM: lymphoangioleiomyomatosis IIP: idiopathic interstitial pneumonitis BO: bronchiolitis obliterans LTx: lung transplant

      Conclusion

      Lung cancer in lung recipients should be screened carefully ever since listing for transplantation.

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    P2.08 - Oligometastatic NSCLC (ID 172)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.08-03 - Clinical Outcome of Patients with Recurrent Non-Small Cell Lung Cancer After Trimodality Therapy (ID 2569)

      10:15 - 18:15  |  Author(s): Shinichi Toyooka

      • Abstract

      Background

      Trimodality therapy, consisting of induction chemoradiotherapy (CRT) followed by surgery, is a potential treatment option for patients with locally advanced (LA) non-small cell lung cancer (NSCLC), such as N2-3, bulky N1, or T3-4 stage disease. However, even after completing this intensive treatment, postoperative recurrence will develop in a subset of patients. Patients with distant metastatic recurrences are generally considered to have systemic disease, which is regarded as incurable. Nevertheless, some patients have a relatively good prognosis following this treatment, even after postoperative recurrence.

      Method

      We analyzed the records of 182 patients with LA-NSCLC who were treated with trimodality therapy between 1999 and 2017 to review the clinical course of those patients and to identify the factors associated with favorable clinical outcome after recurrence. In this study, oligometastasis was defined as one to three metastatic lesions in the brain, or an isolated extracranial metastatic lesion.

      Result

      In 182 patients patients who underwent trimodality therapy for LA-NSCLC, the median follow-up period after the beginning of CRT was 50 months, the median age was 61 years (range, 31–78 years), and Recurrence developed after trimodality therapy in 65 patients (35.7%). The median recurrence-free interval, being the period between the administration of trimodality therapy for the primary tumor and initial recurrence, was 11 months (range, 4.1–73.9 months). Of the 62 of these patients able to be assessed retrospectively, The brain was the most frequent location of recurrence (31%), followed by the lung (27%), lymph nodes (24%), and bone (15%). Twenty-eight had oligometastatic recurrence and 30 underwent local treatment with curative intent. Local treatment was most frequently given to patients with oligometastatic recurrence (P < 0.001). The median post-recurrence survival (PRS) was 15.1 months, and the 2-year PRS rate was 57%. Patients who received local treatment showed better PRS (P = 0.004). The presence of liver metastasis (P = 0.003), bone metastasis (P = 0.034), or dissemination (P < 0.0001) were associated with worse PRS.

      Conclusion

      The survival of patients who received aggressive local treatment for postoperative recurrence after trimodality therapy for LA-NSCLC was better than that of patients who did not.

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    P2.18 - Treatment of Locoregional Disease - NSCLC (ID 191)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.18-12 - Prognostic Nutrition Index Affects Prognosis of Trimodality Therapy for Locally Advanced Lung Cancer with High T Factor (Now Available) (ID 1644)

      10:15 - 18:15  |  Author(s): Shinichi Toyooka

      • Abstract
      • Slides

      Background

      Pretreatment nutritional status critically affects the clinical outcomes. Induction chemoradiotherapy (iCRT) followed by surgery (trimodality therapy) is a high-invasive treatment option for patients with locally advanced non-small cell lung cancer (LA-NSCLC). LA-NSCLC is a heterogeneous disease. Direct invasion into the surrounding structures easily promotes the invasion-related symptoms which inpair quality of life, but lymph node metastasis rarely causes its related symptoms until the bulky metastatic lymph nodes invade the surrounding structures. These differences of disease extent are expected to affect not only clinical outcome of treatment but also nutritional condition before initiation of treatment. While the prognostic nutritional index (PNI) is known to be correlated with the clinical outcomes after surgery in patients with early NSCLC, the significance of the PNI in LA-NSCLC patients undergoing trimodality therapy has not yet been well examined. In this study, we investigated the clinical impact of PNI in the LA-NSCLC patients who underwent iCRT followed by surgery considering the heterogeneity of disease extent.

      Method

      We enrolled 127 patients who received trimodality therapy at our institution between 1999 and 2016. The PNI was examined at all three time-points in the patients: before iCRT, before surgery, and after surgery.

      Result

      Fifty-five and 72 patients were diagnosed as clinical T1/2 (cT1/2) and cT3/4 diseases, respectively, and, 42 and 85 patients were cN0/1 and cN2/3, respectively. The PNI significantly decreased as the treatment progressed among all 127 patients. Patients with cT3/4 disease showed significantly lower PNI values before and after surgery than those with cT1/2 disease. By contrast, the PNIs were equivalent at all time-points between patients with cN2/3 and cN0/1 disease. We performed receiver-operating characteristic curve analysis to determine the cutoff the pre-iCRT PNI for overall survival (OS) in all (n = 127), cT3/4 (n = 72) and cN2/3 patients. The ROC curve analyses indicated that a significant cutoff was identified only in cT3/4 patients. Univariate and multivariate analyses revealed that high pre-iCRT PNI values were significantly correlated with better survival in cT3/4 patients. By contrast, the prognostic impact of pre-iCRT PNI values could not be observed in cN2/3 patients

      Conclusion

      The nutritional status deteriorates as the treatment progresses during trimodality therapy. Intensive perioperative nutritional intervention is required especially for cT3/4 LA-NSCLC patients receiving trimodality therapy.

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