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K.N. Syrigos



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-005 - Bevacizumab (Bv) can be safely administered in pts aged > 80 years old (ID 303)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      Bv is a novel anti-angiogenic agent used in many advanced solid tumours, including non-squamous NSCLC. In contrast to clinical studies where enrolled pts are fit, many elderly NSCLC pts suffer from co-morbidities and often have history of a CVD

      Methods
      Medical records of 2672 pts diagnosed with NSCLC between 2001-2012 were screened. We identified and examined pts ≥75 yrs old treated with bev, for their demographics, clinical data and treatment (Tx) details. We focused on those elderly pts with stable pre-existing cardiovascular disease.

      Results
      356/2672 NSCLC pts received Bv at any Tx line. 33/382 (8,6%) were ≥75 yrs old. Of those, 29 had various co-morbidities including 19 pts with stable CVD on medical Tx. In the 19 pts with CVD the male:female ratio was 17:2 and mean age 77 yrs (range 75-86). 8/19 pts had impaired renal function. All pts were of Performance Status ECOG 0/1. Median number of Bv cycles was 5 (range 2-11). 17/19 pts experienced ≥1 side effects (11 epistaxis and haemoptysis, 5 proteinuria, 4 hypertension) which led to treatment discontinuation in 5 pts. No major/fatal adverse events were noted. 8/19 pts (42%) showed radiological partial response and 5 (19%) stable disease (total disease control rate 61%). Median survival from initiation of Bv till death/last follow up was 7 months (range 2-28, 95% CI 5.14-12.55).

      Conclusion
      Treatment with Bevacizumab seems to be safe and effective in elderly NSCLC patients with controlled pre-existing cardiovascular disease and good PS. These patients might benefit from participation in clinical trials similarly to younger NSCLC patients.

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    P1.17 - Poster Session 1 - Bronchoscopy, Endoscopy (ID 182)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      P1.17-002 - The clinical significance of endobronchial ultrasound in the detection of peripheral pulmonary lesions (ID 339)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      Flexible fiberoptic bronchoscopy (FB) is the standard of care for the evaluation of pulmonary lesions. The aim of the current study is to investigate the effectiveness of EBUS-guided bronchoscopy compared to blind FB techniques in the study of non-visible pulmonary lesions.

      Methods
      We conducted a one year, retrospective, study comparing two populations: In the first one biopsies were performed conventionally (FB-B) with the help of static CT images and in the second biopsies were performed after EBUS- guidance (FB-EBUS). A 20- MHz radial- type ultrasound probe was used to obtain images. Sampling techniques, like bronchial brushing (BR) and transbronchial biopsies (TBB), were conducted in both populations by two separate bronchoscopists. If not a diagnosis was achieved a surgical biopsy or observation strategy was followed.

      Results
      Forty patients appeared with non visible lesions and were included in this study. Twenty patients were examined with the use of EBUS (FB- EBUS) and in twenty cases a conventional FB (FB-B) was conducted. Moreover left lower lobe was the most promising to obtain a diagnosis using ultrasonographic images.

      Conclusion
      Our results suggest that in patients with a non visible pulmonary lesion or SPNs a diagnostic strategy involving EBUS- guided biopsy techniques is a reasonable and effective choice.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 2
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      P2.07-003 - Sampling vs. systematic full lymphatic dissection in surgical treatment of non-small cell lung cancer (ID 340)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      The extent of mediastinal lymph node assessment during surgery for non-small cell cancer remains controversial. Different techniques are used, ranging from simple visual inspection of the unopened mediastinum to an extended bilateral lymph node dissection. Furthermore, there are different terms to define these techniques: Sampling is the removal of one or more lymph nodes guided by preoperative finding. Systematic (full) nodal dissection is the removal of all mediastinal tissue containing the lymph nodes systematically within anatomical landmarks.

      Methods
      A Medline search was conducted to identify articles in English, addressing the role of mediastinal lymph nodes resection in the treatment of NSCLC

      Results
      Opinions favoring full lymphatic dissection include complete resection, improved nodal staging and better local control due to resection of undetected micrometastasis. Arguments against routine full lymphatic dissection are increased morbidity, increased operative time and lack of evidence of improved survival. For complete resection of non-small cell lung cancer a systematic nodal dissection is recommended for many authors, as the standard approach during surgery: it ascertains both adequate nodal staging and completeness of resection.

      Conclusion
      Whether extending the lymph node dissection influences survival or recurrence rate remains to be determined. There are valuable arguments in favor of not only an improved local control but also an improved long-term survival. However, the impact of lymph node dissection in long-term survival should be further assessed by large-scale multicenter randomized trials.

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      P2.07-004 - Wedge Resection and Segmentectomy in Patients with Stage I Non-small Cell Lung Cancer (ID 344)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      The use of resections lesser than lobectomy as definitive management of a stage I non-small cell lung carcinoma (NSCLC) is a topic that creates controversy in the global medical community. To describe the current conclusions concerning the relative indications of each type of resection in the surgical treatment of stage I NSCLC, as well as the international results from their application concerning the local recurrence, disease-free survival, and five-year survival rates.

      Methods
      Thirty four prospective and retrospective studies registered in PubMed and Scopus electronic databases during the last twenty five years were reviewed. Bibliographies and handsearching of journals were used to identify trials. Studies’ authors, citations, objectives, and results were extracted. No meta-analysis was used. Validation of results was discussed.

      Results
      Segmentectomies were superior to wedge resections in terms of local recurrence and cancer-related survival rates. Sublobar resections were superior to lobectomy concerning preservation of pulmonary parenchyma. It was recommended that high-risk patients undergo segmentectomy. Lobectomies were superior to segmentectomies only for tumors >2 cm (T2bN0M0) as regarding disease-free and overall 5-year survival. There was no significant difference for tumors <2 cm in most studies. Free surgical margins were crucial for local control rates. Systematic lymphadenectomy was mandatory regardless of type of resection. In cases of pure bronchoalveolar carcinoma, segmentectomy was recommended. Shorter hospital stay was achieved with sublobar resections.

      Conclusion
      The choice of type of resection for T1aN0M0 tumors should rely on specific patient and tumor characteristics. Patient age and tumor size are the most important factors. Further prospective randomized trials are needed to determine minimal resections in early lung cancer patients.

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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-005 - Erlotinib (E) can be safely administered in pts > 80 years old (ID 345)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      Besides chemotherapy, E is another option in NSCLC pts especially in those with EGFR mutations. Elderly pts enrolled in trials are fit without cM, but in clinical practice most suffer from cM.

      Methods
      Medical records of 1221 pts diagnosed with NSCLC between 2008-2012 were screened. We examined pts ≥75 yrs for demographics, clinical data and Tx details.

      Results
      233/1221 NSCLC pts received E at any line. 53/233 (23%) were ≥75 yrs old. Male:female ratio was 34:19 and median age 79 yrs (range 75-88). NSCLC subtypes included 31 adenoca, 8 squamous cell, 9 NOS and 5 others. 50/53 pts had cM (≥2 in 46 pts, 1 in 4pt). Main cM were cardiovascular disease (n=41), COPD (n=14), other cancer (n=10) and diabetes (n=8). 8 pts were tested for EGFR mutations (5 -ve, 3 +ve). Performance Status was satisfactory (ECOG 0-1) in 8 pts and poor (2-3) in 45pts. 8pts were treated with E 100mg and 45 pts with E 150mg (12 pts needed dose reduction). Complete follow up data were found in 46pts. Mean duration of treatment was 79 days (range 9-662). 35/46 pts experienced side effects (s.e) [rash n=29, diarrhea n=17] which led to treatment discontinuation in 12pts. Pts with abnormal creatinine clearance (n=13) were more likely to stop treatment due to s.e (6/13 versus 6/33). 17/46 pts (37%) achieved disease control (5 PR, 12 SD) and a time to progression (TTP) of 157 days (range 106-662, 95% CI 132.79-270,74) while 22/46 pts had PD as best response (TTP 49d, range 19-88, CI 44,67-64,97). 7pts were not evaluable (stopped Tx due to s.e). All EGFR+ve pts had disease control (2PR, 1SD).

      Conclusion
      E is a valuable option in elderly NSCLC patients with co-morbidities, especially if they harbor EGFR mutations. Impaired renal function might be associated with propensity to side effects and earlyTx discontinuation.

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    P2.13 - Poster Session 2 - SCLC (ID 201)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.13-005 - Palonosetron (Aloxi®) effectively prevents nausea and emesis in SCLC patients receiving platinum-based three days regimen. (ID 2179)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      We evaluated retrospectively the safety and effectiveness of single dose administration of palonosetron (Aloxi®) in SCLC patients receiving platinum-based three days regimen.

      Methods
      We retrospectively recorded the nausea and emesis of 417 SCLC patients (337 men and 80 women) with mean age 69.1 years (SD=9.0 years). Of those 63.3% had Extensive Disease (ED) and 36.7% Limited Disaese (LD). 318 pts (76.3%) received six cycles of chemotherapy and 229 pts (67%) received also radiotherapy, either concurrent or sequential. With regard to the chemotherapy regimen, 290 pts (69.5%) received Carboplatin (D1) & etoposide (D1-3), 99 pts (23.7%) received Carboplatin (D1), Irinotecan (D1) & etoposide(D1-3), and 28 pt (6.7%) received Cicplatin (D1) and etoposide (D1-3). The antiemetic treatment was i.v. administration of 0.25mg palonosetron on D1.

      Results
      315 (75.5%) of 417 patients didn’t experience any acute nausea and 329 (78.9%) patients remained free of nausea in the delayed phase . Free of vomit was 380 (91%) patients in the acute phase and 390 (93.5%) in the delayed phase. In compination 314 (75.3%) patients was free of vomit or nausea in the acute phase and 326 (78.2%) in the delayed phase with the use of palonosetron. No signs or symptoms due to toxicity from palonosetron observed in acute or delayed phase . Both univariate and multiple analyses indicated that the odds of nausea decreases as age increases and that woman had greater odds for nausea. No smoking related differences were recorded, but 94.8% of the patients were smoker. Addition of radiotherapy did not increase the probability of nausea or emesis and patients receiving cisplatin instead of carboplatin were more likely to experience nausea or emesis.

      Conclusion
      Our data indicate that single dose of palonosetron on D1 effectively controls acute and delayed nausea and emesis in SCLC patients receiving platinum based three days regimen.

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    P2.15 - Poster Session 2 - Thymoma (ID 191)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P2.15-004 - Management of primary tumours of the Thymus and usefulness of <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (FDG-PET). (ID 1226)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      Thymic epithelial tumours are the predominant lesions that arise in the anterior mediastinum, represent 0.2—1.5% of all malignancies and overall, it is an uncommon malignancy with an incidence of 0.15 cases per 100,000 population. Recent studies have shown the usefulness of [18]F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating between World Health Organization (WHO) histological subgroups of thymic epithelial tumours. We present our experience in the management of patients with primary thymic tumours.

      Methods
      We evaluated retrospectively the medical records of 21 consecutive patients (pts) who underwent thymectomy in our department. All but one patients underwent radical thymectomy through a median sternotomy. One female patient was subjected to transcervical procedure. In all procedures, the upper and lower thymic poles were traced as far into the neck and down toward the diaphragm as necessary to ensure complete resection, and all fatty tissue between the phrenic nerves was included in the resection. Myasthenia gravis was present in 3 pts (14.28 %), while 9 pts (42.85 %) were asymptomatic.Diagnostic procedures included contrast enhanced Computed Tomography of the thorax (21 pts) and/or Magnetic Resonance Imaging (3 pts) and in the case of 7 patients, an FDG PET-CT was performed. The maximum standardized uptake value (SUV~max~) of the tumor, the mean SUV of mediastinum, and the tumor/mediastinum (T/M) ratio (ratio of peak SUV of the tumor to mean SUV of mediastinum) were compared to determine whether primary thymic tumours could be distinguished by [18]F-FDG PET/CT.

      Results
      There were 11 male and 10 female pts with a mean age of 46.09 years. The histopathology examination revealed 13 thymomas, 1 endocrine carcinoma and 7 hyperplasias. Type A thymomas were found in 2 pts (15.38 %), AB in 5 pts (38.46 %), B1 in 2 pts (15.38%), B2 in 1 pt (7.7 %) and B3 in 2 pts (15.38 %), while 2 thymomas were unclassified. The mean diameter of the resected masses was 7.03 cm. Three pts were classified as Masaoka IIA stage (23.07%) and two as Masaoka IIB (15.38%), who received adjuvant radiotherapy. All the others were classified as Masoka I. All tumours were totally resected. The 5 year survival was 100%. There was recurrence of the endocrine carcinoma within 5 years and the pt underwent a reoperation.The SUV~max ~values of thymomas were 2.31+/- 0.59, while the SUV~max~ values of mediastinum were 1.74 +/- 0.08.

      Conclusion
      Tumours of the thymus are an heterogeneous group of tumours, ranging from relatively “benign”thymomas to highly aggressive carcinomas. Surgery continues to be the mainstay of treatment and complete resection of the tumour remains the most important prognostic factor. A recurrence should be completely resected whenever possible, because this approach is associated with good long-term survival. FDG-PET can help characterize various thymic lesions, however, larger prospective studies are further required to substantiate these findings.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-004 - Jaw Osteonecrosis in lung cancer patients: a retrospective analysis (ID 305)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      Lung cancer patients may develop oral complications related to conventional chemotherapy or targeted and antiresorptive agents. Early diagnosis of those complications, within a multidisciplinary team, can lead to effective treatment and the maintenance of patient’s quality of life. The aim of the current study is to present our 4-year experience (2009-2012) in the treatment and prevention of oral complications in lung cancer patients.

      Methods
      Forty three patients (21 women, 22 men, mean age 62.6 years) were included in the analysis. Thirty patients received active chemotherapy treatment; 9/30 (30%) received conventional chemotherapy in combination with targeted therapy, 11/30 (36.7%) targeted therapy and 10/30 (33.3%) conventional chemotherapy. Twenty-one patients received i.v. bisphosphonates (zoledronate 76.2%). Eleven patients received bishosphonates combined with bevacizumab; 4 of them had interrupted bevacizumab at the time of referral. Oral clinical and radiographic evaluation, using periapical and panoramic x-rays were performed. Dental scan was performed in 2 patients. Oral hygiene instructions were introduced and patients were educated about the importance of the maintenance of optimal oral health.

      Results
      Thirty three patients were referred by their medical oncologist (25 patients, 58.1%, by the SOTIRIA Hospital), 1 was referred by his dentist and 10 were self referred. Twelve patients (27.9%) presented with jaw osteonecrosis (Stage 0: 6, 50%, Stage I: 4, 33.3%, Stage II: 2, 16.7%); of those 4 received bevacizumab concurrently with zoledronic acid, 2 received the same combination in the past, 5 received zoledronate alone and 1 received zoledronate followed by denosumab. Six patients were diagnosed with oral candidiasis, 4 with herpes infection, and 2 with necrotizing ulcerative gingivitis. Nine patients had dental problems, while 5 patients were introduced to the Unit for preventive measures. Jaw osteonecrosis was treated with long term antibiotics, while local ozone oil was applied in 3 patients. Three dental extractions were performed in one patient with osteonecrosis stage 0. Today, 6 patients with osteonecrosis remain in partial remission, 3 are in complete remission, 2 were lost of follow up and 1 worsened. Of the 3 dental extractions, 2 healed and one led to osteonecrosis stage I. Patients with dental problems were further referred to their family dentists.

      Conclusion
      Osteonecrosis of the jaw, in the present series, was the most common oral complication. The dental oncology expert within in the multidisciplinary team contributed to the diagnosis of oral pathoses and of the osteonecrosis at the early Stage 0.

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    P3.14 - Poster Session 3 - Mesothelioma (ID 197)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P3.14-002 - Second Line- Chemotherapy Treatment Options, In Malignant Mesothelioma Tumors, Resistant To Pemetrexed. (ID 343)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      The number of patients with Malignant Mesothelioma is expected to increase over the next ten years from the number of 3.300 new cases that are reported annually nowadays. Most of the patients appear with advanced, surgically unresectable disease at the time of diagnosis and relapse is usual after the standard 1st line treatment with a platinum-pemetrexed doublet, due to intrinsic and acquired resistance to pemetrexed. This review focuses on the treatment options in Malignant Mesothelioma resistant to pemetrexed and is based on trials for possible 2nd line regimens tested the last ten years and ongoing trials of novel agents and studies exploring the basis of pemetrexed resistance.

      Methods
      We searched via PubMed/Medline, Clinicaltrials.gov and American Society of Clinical Oncology databases for articles and ongoing trials published until 1/2013 using the term: “mesothelioma”, in association with “2nd line chemotherapy”, “pemetrexed resistance”, “relapsed”, “pemetrexed-pretreated” and “biomarker”. Primary sources have been quoted.

      Results
      Data from forty eight conducted and ongoing trials, mainly phase II, single-armed, but also retrospective and phase III, are shown and discussed. Thirty different agents were tested in these trials as possible 2nd line drugs for Malignant Mesothelioma. Currently, no guidelines for 2nd line chemotherapy in Malignant Mesothelioma tumors resistant to pemetrexed are available.

      Conclusion
      In the absence of a “gold standard” as 2nd line treatment for Malignant Mesothelioma, results of ongoing trials are eagerly awaited and the research for novel agents remains critical. Furthermore, additional research should be done towards the understanding of the mechanisms that lead to pemetrexed resistance, the possible personalization of 1st and 2nd line treatment and the use of biomarkers that can be used as factors predicting the resistance itself. Finally, more patients should be convinced to enroll in clinical trials and more randomized trials have to be conducted.

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    P3.23 - Poster Session 3 - Tobacco Control, Prevention and Chemoprevention (ID 164)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P3.23-001 - The clinical significance of smoking cessation in patients with cancer (ID 342)

      09:30 - 09:30  |  Author(s): K.N. Syrigos

      • Abstract

      Background
      Despite the established causal relationship between tobacco smoking and cancer many cancer patients continue to smoke after diagnosis. This partly reflects the ignorance of the beneficial effects of smoking cessation even after diagnosis. The aim of the study is to demonstrate the effect of continuing or quitting smoking in patients with diagnosed cancer.

      Methods
      This study is based on a review of medical databases (Pub Med CENTRAL, MEDLINE, Cochrane Library) of the last thirty years. All articles included in the present analysis were in English.

      Results
      In patients with early stage lung cancer, continued smoking after diagnosis is associated with an increased risk of all cause mortality and decreased survival. Research has demonstrated significant difference in actuarial overall survival favoring the non-smoking group among patients with lung cancer. In patients with oral cancer smoking cessation or reduction leads to a significant reduction in mortality. There is also evidence that tobacco smoking exacerbates and prolongs radiotherapy induced complications.Of particular importance is the evidence that continued smoking is associated with adverse effects during anticancer treatment. Smoking increases tumor progression and resistance to chemotherapy due to nicotine-induced resistance to apoptosis by modulating mitochondrial signaling. Continuing smoking is also related with inferior outcomes during treatment with novel targeted therapies such as erlotinib. Continuing smoking in gastric and lung cancer patients is also associated with an increased risk of developing second primary tumors. Quitting smoking after lung cancer diagnosis is associated with better performance status while persistent smokers have worse overall quality of life. Patients who continued to smoke despite being diagnosed with cancer report more severe pain than never smokers and a greater interference from pain.

      Conclusion
      Continuing smoking after cancer diagnosis is related with reduced treatment efficacy and reduced survival, risk for more secondary malignancies and deterioration in quality of life.