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H. Koyi
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-022 - Establishing Reflex NGS Testing in NSCLC in a Regional Network of County Hospitals in Central Sweden (ID 4759)
14:30 - 14:30 | Author(s): H. Koyi
- Abstract
Background:
Extended genetic testing of NSCLC tumor samples provides a foundation for personalized cancer treatment and use of new targeted medication. Testing with Next Generation Sequencing (NGS), mostly performed at university hospitals, has not been available for all patients due to geographic and economic reasons. Many lung cancer patients carry a heavy burden of disease and extensive travelling can negatively impact quality of life. The ability to perform a modern state-of the art work-up at local hospitals, without compromising on diagnostic quality, will enable equal access to personalized treatment for lung cancer patients.
Methods:
In Gävle County hospital routine diagnostic immunohistochemistry (IHC) on biopsies is performed at the local pathology lab. In the case of NSCLC the formalin-fixed, paraffin embedded (FFPE) tissue samples are sent to Uppsala University hospital for further molecular pathology and NGS testing. A targeted NGS test (18 gene panel) was established for mutation screening of small biopsies and cytology specimens (Moens et al., J Mol Diagn, 2015). Fusion genes - ALK, ROS1 and RET - are analysed by IHC, FISH and nanoString. Structured biobanking of surplus biopsies and blood samples during treatment, for explorative biomarker testing and research, was set up as a regional extension of the UCAN infrastructure, including detailed registration of clinical baseline and real-time follow-up data in a dedicated database.
Results:
Inclusion of patients in the biobanking cohort started gradually during 2015 in Uppsala, and in February 2016 in Gävle. The cumulative inclusion in the UCAN biobank is updated at www.u-can.uu.se (see Statistics). To date (July 2016) 70 patients have been included at Gävle County hospital covering 95% of the newly diagnosed NSCLC patients. So, far 242 patients from the region were tested by NGS yielding 23 EGFR+ (9.5%), 75 KRAS+ (31%), 5 BRAF+ (2.1%, codon 600), 2 MET (0.8%, exon 14 skipping), 1 ERBB2 (0.4%, exon 20 insertion), and 6 PIK3CA (2.5%, exon 9/20) cases. Fusion gene analysis resulted in 5 ALK+ (2.1%), 1 ROS1 and 1 RET patients.
Conclusion:
Decentralised local patient care, tissue/blood sampling and biobanking in combination with centralised molecular testing allows advanced lung cancer diagnostics and clinical research in networks of county hospitals. Survival benefits from modern targeted drugs, for national lung cancer cohorts, can only be achieved and evaluated in population-based settings without bias related to selective referral to major cancer centers.
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P1.02-063 - Mutation Profiling by Targeted Next-Generation Sequencing of an Unselected NSCLC Cohort (ID 4147)
14:30 - 14:30 | Author(s): H. Koyi
- Abstract
Background:
Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with a wide diversity when it comes to molecular variations. In the non-squamous subset a large variety of altered driver genes have been identified.
Methods:
The mutational status was evaluated in a consecutive Swedish NSCLC cohort consisting of 354 patients, who underwent surgical resection between 2006 and 2010. DNA was prepared from either fresh frozen or formalin fixed paraffin embedded tissue (FFPE) and used for library preparation using a Haloplex gene panel and subsequently sequenced on an Illumina Hiseq instrument. The gene panel covers all exons of 82 genes, previously identified in NSCLC. The panel design utilizes two strand capture and reduced target fragment length compatible with degraded FFPE samples (Moens et al., J Mol Diagn, 2015).
Results:
All previously known hotspot alterations in the driver genes KRAS, EGFR, HER2 (exon 20 insertions), NRAS, BRAF, MET (exon 14-skipping) and PIK3CA (exon 9 and 20) were analyzed in the 252 non-squamous cases, see figure. KRAS mutations were found in 98 patients (39%) whereas EGFR alterations were present in 33 (13%). The prevalence of KRAS mutations is higher than normally reported and could be due to the large fraction of smokers included in this cohort. The EGFR prevalence is a bit higher than previously demonstrated (Sandelin et al. Anitcancer Res, 2015). Mutations in the other driver genes were detected at low frequencies (HER2(3%), BRAF(2%), NRAS(1%), MET(1%) and PIK3CA(1%)). Figure 1
Conclusion:
The preliminary analysis of mutational status in this large unselected Swedish NSCLC cohort reveals mutation frequencies in the common driver genes resembling previous reports on western populations with a high smoking rate. Ongoing analysis of the remaining genes will be used for pathway analysis and could provide a more complete picture of the lung cancer pathogenesis.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-008 - Clinical Importance of Indolent Lung Cancers (ID 4076)
14:30 - 14:30 | Author(s): H. Koyi
- Abstract
Background:
The occurrence and importance of “indolent” lung cancers is intensely discussed. In the National Lung Cancer Study Trial (NLST) (1) it was estimated that 18% of all cancers were indolent (2). This was based on comparison with the controls being “the golden standard”, i.e. assuming that there were no indolent cancers among those. However, studies in the 20th century with X-ray screening for lung cancers showed the incidence of indolent tumors to be around 25% in such materials.
Methods:
We have made some calculations of the NLST material based on the difference in numbers of lung cancers found at the first screening and the subsequent yearly ones.
Results:
Simple estimation: the 5-year “normal” survival of all lung cancers is 16%; in the NLST X-ray arm only (the controls) it was 53%. If 25% is due to indolence , 12% (53 minus 16 minus 25) must be due to selection. In the screened arm (low CT) , 66% cent were alive, and thus, 38% (66 minus 16 minus 12) must be due to indolent cancers. A sophisticated calculation: The difference in numbers of discovered cancers at first and following screenings in the screened arm only (thus disregarding the controls) can be used to give an indication of the proportion of indolent cancers. This will also result in a percentage of indolent cancers of around 40.
Conclusion:
Screening for lung cancer with low-dose CT has been proven to save lives. However, this comes with the risk of doing more harm than good to those who actually have an indolent cancer. Of all confirmed and staged patients in the CT arm of the NLST, 70 per cent were stage I and II, and almost all of them had surgery. The indolent cancers would be included among these, and if 30% of all cases they will amount to two thirds of the operated patients. Hopefully, new studies might make it possible to discriminate between indolent and life-threatening tumors. In the meantime, we should choose therapies with as little side effects as possible, even if these methods do not maximize the possibility of cure. 1. National Lung Cancer Screening Trial Research Team. Reduced lung cancer mortality with low-dose computed tomography screening. New Engl J Med 2011; 365:395-409. 2. Patz EF, Pinsky P, Gatsonis et al. Over-diagnosis in low-dose computed tomography screening for lung cancer. JAMA Int Med 2014; 174:269-274.
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-008 - Non-Small Cell Lung Cancer in Octogenarians: Real-Life Clinical Practice; Characteristics, Therapy and Survival (ID 4034)
14:30 - 14:30 | Author(s): H. Koyi
- Abstract
Background:
Globally, more people are surviving to older age; consequently, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice.
Methods:
A retrospective observational study of all elderly (>80 years) patients with NSCLC referred to Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010 and followed until June, 2016.
Results:
During the period 2662 patients were newly diagnosed with lung cancer. 485 (12.2%) were 80 years or older. 33 (6.8%) hade small cell lung cancer and were excluded, leaving 452 for the study. 216 (47.8%) were male. Mean, median, and range age for males were 83.8, 83, and 80-96 years, respectively. These figures for females were 83.7, 83, and 86-95. 28 (6.2%) of the population were 90 years old or older. 77.8% patients were current or former smokers with significant differences between the genders (p<0.001). There was no difference in performance status (PS) between the genders (p<0.93), with PS 0-1 in 45%, PS2 in 26% and PS3-4 in 29%. 33.9% of patients were diagnosed in stages 1-II, 34.1% in stage III and 31.9% in stage IV. Most of the patients, 45.6%, had adenocarcinoma, 18.1% squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. There were significant differences in treatment modalities (p=0.040). Chemotherapy was given in 9.5%, local radiotherapy in 17%, stereotactic body radiotherapy (SBRT) in 10.6%, 6.9% underwent surgery and 209 (46.2%) were not given any therapy. Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth line. Median overall survival was 115 days in patients given no therapy and 362 days in patients given any therapy. Patients who underwent surgery had a median overall survival of 5,6 years compared to 3,5 years for patients given SBRT (p=0.0187). There were no significant differences in survival between genders.
Conclusion:
Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-013 - Chemotherapy is Beneficial for Octogenarians with Non-Small Cell Lung Cancer (NSCLC) (ID 4354)
14:30 - 14:30 | Author(s): H. Koyi
- Abstract
Background:
In Sweden, almost half of the patients diagnosed with lung cancer diagnosis are more than 70 years old and indeed14% were 80 years and older. Treatment of the elderly with lung cancer has, therefore, become an important issue. In the Stockholm county, almost all patients with lung cancer are preferred to Karolinska University Hospital. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) treated with chemotherapy responded in real-life clinical practice
Methods:
A retrospective observational study of all elderly (>80 years) patients with NSCLC referred to Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Sweden, 2003-2010 and followed until June, 2016
Results:
In total, 2350 patients were newly diagnosed with lung cancer during this period. 453 (19.2%) were 80 years or older and had NSCLC. Of these 51(11 %) received chemotherapy. In that group, mean and median age was 82 years (range 80-89). 86% were current- och ex-smokers. 70% had PS 0-1, 27% PS 2, and 2% PS 3. 92% had stage III-IV. Adenocarcinoma was the most prevalent histology type (59%) and squamous cell carcinoma was second (24%). 61% received carboplatin/gemcitabine, 8% carboplatin/vinorelbine, 12% gemcitabine only, and 16% vinorelbine only. Most patients (47%) received at least four cycles and another 6% three cycles. Chemotherapy dose reduction/ termination occurred in 12% due to hematologic toxicity, in 18% to non-hematologic toxicities, and in 4% because of progressive disease. In total, therefore, 53% completed their treatment. 59% hade stable disease, 33% partial response, and 9% progressive disease. 22% received second line, 10% third line, but only one patient (2%) 4[th] line treatment. The median overall survival was 281days in male patients and 332 days in females (NS).
Conclusion:
Treatment of elderly NSCLC patients with good PS with chemotherapy is feasible and appears to prolong survival.
