Characteristics of non-small-cell lung cancer with interstitial pneumonia: variation in cancer location, histopathology, and frequency of postoperative acute exacerbations in interstitial pneumonia

Abstract Background Non–small-cell lung cancer (NSCLC) has been reported to develop in patients with interstitial pneumonia (IP); however, clinical, radiological, and pathological features remain to be elucidated. Methods We retrieved the records of 120 consecutive NSCLC patients associated with IP who underwent surgery at Toranomon Hospital between June 2011 and May 2017. We classified the patients into three groups according to NSCLC location using high-resolution computed tomography: group A, within a fibrotic shadow and/or at the interface of a fibrotic shadow and normal lung; group B, within emphysematous tissue and/or at the interface of emphysematous tissue and normal lung; and group C, within normal lung. In 64 patients, programmed death ligand-1 (PD-L1) status was assessed with immunohistostaining. Results Most of the patients (89; 70%) were classified as group A. This group tended to have squamous cell carcinoma with the usual interstitial pneumonia (UIP). These cancers were located mainly in the lower lobes and seven of the eight postoperative acute exacerbations (pAE) of IP developed in this group. NSCLC in the group B were mainly squamous cell carcinomas located in the upper lobes. No patient with PD-L1 negative was classified into group B. None of the patients in group C showed UIP. and most of the cancers were adenocarcinoma. The frequency of epidermal growth factor receptor mutation-positive NSCLC was the highest in this group. Conclusions The three groups each showed characteristic features in terms of tumor location, histopathology, PD-L1 expression, and frequency of pAEof IP.

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The effect of nivolumab treatment for central nervous system metastases in non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20601 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20601-e20601 ◽

Cited By ~ 7

Author(s):

Hiromi Watanabe ◽

Toshio Kubo ◽

Takashi Ninomiya ◽

Kadoaki Ohashi ◽

Eiki Ichihara ◽

...

Keyword(s):

Lung Cancer ◽

Central Nervous System ◽

Nervous System ◽

Small Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Group A ◽

Group B ◽

Nsclc Patients ◽

Cns Lesions

e20601 Background: Central nervous system (CNS) metastases (mets) occur in 30% of patients with advanced non-small cell lung cancer (NSCLC) and are associated with poor overall survival (OS). Although nivolumab, a programmed death-1 immune checkpoint inhibitor antibody, has demonstrated a longer survival benefit compared with docetaxel in previously treated NSCLC patients (CheckMate 017 and 057; N Engl J Med, 2015), patients with symptomatic or untreated CNS mets were excluded in these trials. In CheckMate 012 Arm M, 2 of 12 patients (16.7%) with untreated CNS mets showed intracranial responses, but the effect of nivolumab treatment for CNS mets was not fully investigated. Methods: To investigate the effect and safety of nivolumab for CNS mets in NSCLC patients, we retrospectively analyzed 48 patients with NSCLC who were treated with nivolumab from February 2016 to December 2016 at Okayama University Hospital. Results: Twenty-nine patients (60%) had no CNS lesions (group A) and 19 patients (40%) had brain mets (BM) (group B). In group B, 15 patients (79%) received radiotherapy (RT) for BM, including 5 patients who received RT just before nivolumab treatment. The responses of extra-CNS lesions to nivolumab are shown in the table. The PFS was longer in group A than in group B (p=0.14). In group B, the PFS of patients who received prior RT tended to be longer than in those without RT (p=0.42); OS was not reached in either group. In group B, the effects of nivolumab treatment for CNS mets were evaluated in 12 patients: SD occurred in 3 patients (25%), PD in 4 patients (33%), and NE in 5 patients (42%). All 4 patients with PD in the CNS lesion also showed PD in the extra-CNS lesion. In group A, no patients showed progression only in the CNS lesion. Conclusions: In this retrospective study, there were no patients treated only with nivolumab who showed a response to CNS mets. RT prior to nivolumab might be more effective, so future investigations should involve additional cases and prospective studies. [Table: see text]

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The association between STK11/LKB1 and/or KEAP1 mutations and response to PD-1/PD-L1 inhibitors in patients with advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21538 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21538-e21538

Author(s):

Meagan Elizabeth Miller ◽

Meera Patel ◽

Sandra K. Althouse ◽

Nasser H. Hanna ◽

Hirva Mamdani

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Concurrent Chemotherapy ◽

Small Cell ◽

Small Cell Lung ◽

Disease Characteristics ◽

Clinical Databases ◽

Group A ◽

Group B

e21538 Background: Advanced non-small cell lung cancer (NSCLC) patients with tumors harboring STK11/LKB1 or KEAP1 mutations have inferior treatment outcomes when treated with PD-1/PD-L1 blockade, regardless of KRAS status, PD-L1 score, or TMB score (Skoulidis et al, Cancer Discovery 2018, ASCO abstract 102, 2019). Methods: Retrospective clinical databases from Indiana University and Karmanos Cancer Institute were queried to identify patients from 2008-2019 with advanced NSCLC treated with PD-1/PD-L1 monotherapy (group A) or concurrent chemotherapy + PD-1/PD-L1 inhibitors (group B) whose tumors harbored STK11/LKB1 and/or KEAP1 mutations. Patients were characterized by best response, progression of disease (PD) or non-PD (complete response (CR) + partial response (PR) + stable disease (SD)). Patient and disease characteristics, response, and duration of response (> vs. < 6 months) were recorded. Results: A total of 77 patients met the above criteria (55 in group A, 22 in group B). 52 of 55 patients in group A received prior chemo. Patient and disease characteristics and outcomes are summarized in the table. Conclusions: STK11/LKB1 and/or KEAP1 mutations are independent of PD-L1/TMB status, although most patients had PD-L1 of <1%. Nearly ½ of patients with STK11/LKB1 and/or KEAP1 mutations achieve at least SD with PD-1/PD-L1 inhibitor monotherapy and more than 50% of those with non-PD maintain that response status for > 6 mos. The frequency and duration of non-PD in this population is higher in patients receiving chemotherapy + PD-1/PD-L1 concomitantly. [Table: see text]

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Sequential Treatment of Afatinib and Osimertinib in Patients with Advanced Non-small Cell Lung Cancer Harboring EGFR Mutations: Results from a Real-world Study in South Korea

10.21203/rs.3.rs-215079/v1 ◽

2021 ◽

Author(s):

Taeyun Kim ◽

Tae Won Jang ◽

Chang Min Choi ◽

Mi-Hyun Kim ◽

Sung Yong Lee ◽

...

Keyword(s):

Lung Cancer ◽

South Korea ◽

Small Cell Lung Cancer ◽

Survival Rates ◽

Small Cell ◽

Egfr Mutations ◽

Small Cell Lung ◽

Group A ◽

Group B ◽

Egfr Mutated

Abstract The optimal sequence for administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non-small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations. Electronic records of patients with EGFR-mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and October 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Of the 737 patients who received frontline afatinib treatment, 360 with complete records were selected (group A:154, group B: 206). The median TOT was 33.9 months (95% confidence interval [CI]: 24.5−43.3) in group A and 21.3 months (95% CI: 19.4−23.1) in group B. The median TOT with afatinib was 12.9 months (95% CI: 11.8−14.0) overall, and 15.2 months (95% CI: 13.2−17.1) in group A. The 2- and 3-year survival rates were 86.0% and 69.3% in group A and 75.9% and 55.3% in group B, respectively. Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies. Therefore, this sequential treatment strategy may offer clinical benefits to patients with EGFR-mutated NSCLC.

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Thymidylate synthase polymorphisms and immunohistochemistry in non-small cell lung cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.11101 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 11101-11101

Author(s):

J. Stoehlmacher ◽

E. Goekkurt ◽

G. Hoeffken ◽

R. Zinsky ◽

F. Lynch ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Cell Lung Cancer ◽

Staining Intensity ◽

Small Cell ◽

Small Cell Lung ◽

Histological Subtypes ◽

Group A ◽

Group B

11101 Background: Recently, pemetrexed has been introduced into the treatment of non-small cell lung cancer (NSCLC). There's evidence that pemetrexed appears to be more efficient in non squamous NSCLC including adenocarcinoma (AC) and large cell carcinoma (LCC). TS represents a major target enzyme of pemetrexed. We evaluated the expression of TS among different histological types of NSCLC and its association with functional genetic polymorphisms of the TS gene. Methods: Archived tumor samples from 312 individuals with NSCLC were analyzed. Immunohistochemistry (IHC) was performed using a mouse monoclonal antibody to TS. TS stained sections were scored for cytoplasmic and nuclear localization. For each compartment, the tumor was evaluated for the estimated percentage of positive cells with the greatest intensity within the tumor. Intensity was scored on a scale of 0–4. A score of 3–4 was classified as high expression. Genotyping of TS-VNTR including the G/C SNP and TS1394del6 was performed by PCR based RFLP techniques. Genotypes supposed to be associated with low expression were grouped (group A: 2R/2R or 2R/3RC or 3RC/3RC + -6/-6) and compared to genotype groups associated with high expression (group B: 2R/3RG or 3RC/3RG or 3RG/3RG + -6/+6 or +6/+6). Results: IHC and polymorphisms could be performed successfully in 312 (100%) and 287 (92%), respectively. Distribution of histology was as follows: 50% AC, 42% squamous cell carcinoma (SCC), 3% LCC and 5% mixed or other histological subtypes. Group B genotypes were significantly more present in SCC than in AC (49% vs 23%, p=.002). Tumors with group B genotypes were more likely to display high nuclear staining intensity than group A tumors (30% vs. 17%, p=.077). A similar but not significant trend was seen for cytoplasmic staining intensity. There was no significant difference between histological subtypes of NSCLC with respect to TS protein expression. AC were more common than SCC to show a G1 differentiated tumors (8% vs 1%, p<.001). No difference between genotype groups were observed with respect to grading. Conclusions: TS polymorphisms are significantly associated with histology subtypes in NSCLC. These results represent a potential explanation for efficacy differences of pemetrexed in NSCLC and warrants further investigations. [Table: see text]

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Survival outcome of tyrosine kinase inhibitors beyond progression in association to radiotherapy in oligoprogressive EGFR-mutant non-small-cell lung cancer

Future Oncology ◽

10.2217/fon-2019-0349 ◽

2019 ◽

Vol 15 (33) ◽

pp. 3775-3782 ◽

Cited By ~ 2

Author(s):

Sabrina Rossi ◽

Giovanna Finocchiaro ◽

Vincenzo Di Noia ◽

Maria Bonomi ◽

Eleonora Cerchiaro ◽

...

Keyword(s):

Lung Cancer ◽

Tyrosine Kinase ◽

Small Cell Lung Cancer ◽

Disease Progression ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Group A ◽

Group B

Aim: The association of tyrosine kinase inhibitors (TKIs) and local radiotherapy in EGFR-mutated non-small-cell lung cancer patients experiencing disease progression under TKIs could be a valid an option. Patients & methods: We included 131 patients experiencing disease progression during first-line TKI. In group A, patients received TKI beyond progression and site(s) of progression were irradiated; in group B, patients remained on TKI alone beyond progression; and group C stopped TKI at first disease progression. Results: Median overall survival resulted longer in group A versus B and C (p < 0.0001). Group A had a trend toward a longer second progression-free survival (measured from the time of first progression until second progression) versus group B (p = 0.06). Conclusion: TKI beyond progression in association with local ablative treatment is a valid treatment option in oligoprogressive patients.

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Paclitaxel Plus Carboplatin Versus Gemcitabine Plus Paclitaxel in Advanced Non–Small-Cell Lung Cancer: A Phase III Randomized Trial

Journal of Clinical Oncology ◽

10.1200/jco.2002.12.112 ◽

2002 ◽

Vol 20 (17) ◽

pp. 3578-3585 ◽

Cited By ~ 202

Author(s):

Paris Kosmidis ◽

Nick Mylonakis ◽

Costas Nicolaides ◽

Charalabos Kalophonos ◽

Epaminontas Samantas ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Response Rate ◽

Randomized Study ◽

Small Cell ◽

Phase Iii ◽

Small Cell Lung ◽

Group A ◽

Group B

PURPOSE: We conducted this randomized study comparing the activity and toxicity of paclitaxel and gemcitabine (PG) and paclitaxel and carboplatin (PC) combinations for the treatment of advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to paclitaxel 200 mg/m2 on day 1 plus either carboplatin at an area under the concentration-time curve of 6 on day 1 (group A) or gemcitabine 1,000 mg/m2 on days 1 and 8 (group B) every 3 weeks. A retrospective cost analysis was conducted using Student’s t test to compare independent samples between groups. RESULTS: A total of 509 patients (group A, 252 patients; group B, 257 patients) were enrolled; all characteristics were well balanced. The median survival time was 10.4 months (95% confidence interval [CI], 8.8 to 12 months) for group A and 9.8 months (95% CI, 8.0 to 11.7 months) for group B (P = .32). Respective 1-year survival rates were 41.7% and 41.4%. The response rate for group A was 28.0% (2% complete response [CR], 26% partial response [PR] [95% CI, 22% to 34%]), and the response rate for group B was 35.0% (5% CR, 30% PR) [95% CI, 29% to 41%]) (P = .12). Toxicity was mild. Grades 3/4 neutropenia, thrombocytopenia, and anemia for groups A and B were seen in 15% and 15%, 2% and 1%, and 5% and 2%, respectively. The mean total cost (outpatient clinic visits plus chemotherapy drug fee) for group A (€ 7,612.64) versus group B (€ 7,484.77) was not statistically significant (P < .66). CONCLUSION: The PG combination is as equally active and well tolerated as the PC combination in patients with advanced NSCLC.

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Extra cost of brain metastases (BM) in patients with non-squamous non-small cell lung cancer (NSCLC): a French national hospital database analysis

ESMO Open ◽

10.1136/esmoopen-2018-000414 ◽

2018 ◽

Vol 3 (6) ◽

pp. e000414 ◽

Cited By ~ 9

Author(s):

Nicolas Girard ◽

Delphine Cozzone ◽

Lucie de Leotoing ◽

Charlène Tournier ◽

Alexandre Vainchtock ◽

...

Keyword(s):

Lung Cancer ◽

Palliative Care ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Incremental Cost ◽

Small Cell ◽

Small Cell Lung ◽

Group A ◽

Group B

PurposeTo assess the incremental cost associated with the management of patients with primary non-squamous non-small cell lung cancer (NSCLC) with brain metastases at the time of diagnosis.MethodsData were extracted from the French Hospital medical information database (Programme de Médicalisation des Systèmes d’Information (PMSI)). Patients with non-squamous NSCLC were identified through a diagnosis of lung cancer and a prescription of bevacizumab or pemetrexed. All such patients hospitalised with lung cancer for the first time in 2013 and with metastases identified at the first hospitalisation were eligible. Two cohorts were identified, one with brain metastases (group B: n=971) and one with metastases at other sites (group A: n=1529). For each patient, total in-hospital medical resource consumption associated with the initial hospitalisation in 2013 and with any follow-up stays in the following 24 months was documented. Costs were attributed from official French national tariffs and expressed in 2017 euros.ResultsThe mean number of hospitalisations per patient in the 24-moth follow-up period was 17 in group A and 21 in group B. >99% of patients in both groups received chemotherapy. 58% of patients in group B and 13% in group A were managed by radiotherapy. 37% in group B and 24% in group A received palliative care. The associated cost was €2979 per patient-month for patients in group B and €2426 for patients in group A, representing a differential cost of €553 per month. Radiotherapy (+€164/month) and palliative care (+€130/month) were the principal drivers of the incremental cost.ConclusionsThe presence of brain metastases at the time of diagnosis of non-squamous NSCLC carries a significant burden, and ways of lowering this burden are needed.

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Effectiveness of S-1 Monotherapy for Non-small-cell Lung Cancer Associated with Interstitial Pneumonia

Haigan ◽

10.2482/haigan.57.184 ◽

2017 ◽

Vol 57 (3) ◽

pp. 184-189

Author(s):

Takahiro Yoshizawa ◽

Kazutoshi Isobe ◽

Kyohei Kaburaki ◽

Hiroshi Kobayashi ◽

Go Sano ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Interstitial Pneumonia ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

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The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190410151945 ◽

2019 ◽

Vol 22 (4) ◽

pp. 238-244 ◽

Cited By ~ 2

Author(s):

Gang Chen ◽

Bo Ye

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Cell Lung Cancer ◽

Small Cell ◽

Nsclc Cell ◽

Normal Lung ◽

Migration And Invasion ◽

Small Cell Lung ◽

Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

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