Oligometastasis is a state in which cancer patients have a limited number of metastatic tumors; patients with oligometastases survive longer than those with polymetastases. Extensive disease ...(ED)-small cell lung cancer (SCLC) is considered a systemic disease and a poor survival. This study investigated whether the concept of oligometastases is prognostic factor also applicable to patients with ED-SCLC.
We performed a retrospective study of 141 consecutive patients with ED-SCLC between 2008 and 2016. The patients were divided into four subgroups: group 1; patients with solitary metastatic site in one organ (n = 31), group 2; patients with 2-5 metastatic sites in one organ (n = 18), group 3; patients with over 6 metastases in one organ (n = 15), and group 4; patients with 2 or more metastatic organs (n = 77).
It was identified that 49 patients with ED-SCLC had oligometastases (groups 1 + 2) and 92 had polymetastases (groups 3 + 4). The prognoses of patients with ED-SCLC and oligometastases, defined as ≤5 metastases in a single organ, were significantly superior to those of patients with polymetastases 16.0 (95% CI, 11.0-21.0) months vs. 6.9 (95% CI, 6.0-7.8) months; p<0.001. 43 of 49 patients with ED-SCLC and oligometastases were relapsed after initial chemotherapy, and 38 (88%) experienced local recurrence.
Patients with ED-SCLC and oligometastases may have improved survival than those with polymetastases. As oligometastatic ED-SCLC tends to recur locally, local therapy combined with systemic chemotherapy may be a treatment option.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Objective
. The clinical outcomes of poor performance status (PS) patients with
epidermal growth factor receptor
(
EGFR
)-mutated non-small cell lung cancer (NSCLC) who are treated with ...osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive
EGFR
mutations.
Materials and Methods.
We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in
EGFR
. All patients were administered osimertinib (80 mg/day) as the initial treatment.
Results.
Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78 years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred.
Conclusion.
Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive
EGFR
mutations. To obtain conclusive results, further studies with larger cohorts are warranted.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
NAP1L1 is a key regulator of embryonic neurogenesis but its role in lung cancer remains unexplored. In this study, we investigated the relationship between NAP1L1 expression and the ...clinicopathological parameters and prognosis of non-small cell lung cancer patients. To this end, the expression of NAP1L1 in tumor samples was evaluated by immunohistochemistry. NAP1L1 expression was significantly associated with reduced differentiation (P = 0.00014), higher pathological TNM stages (P < 0.00001), lymph node metastasis (P < 0.00001), intrapulmonary metastasis (P = 0.02955), lymphatic invasion (P = 0.00019), vascular invasion (P = 0.00008) and poorer prognosis (P = 0.0008) of patients with adenocarcinoma. Moreover, multivariate analyses using the Cox-proportional hazards model confirmed that NAP1L1 expression increased the risk of death after adjusting for other clinicopathological factors (HR = 2.46, 95% CI, 1.22–4.96). Furthermore, NAP1L1 expression was identified as an independent poor prognostic factor in patients with resectable stage I lung adenocarcinoma. NAP1L1-siRNA-treated lung adenocarcinoma-derived A549 cells showed significant suppression of proliferation, migration, and invasion abilities. These findings suggest that NAP1L1 may be a novel predictive and prognostic marker in lung adenocarcinoma, particularly in those with stage I of the disease.
Summary
Background
Exon 19 deletion and L858R point mutation in exon 21 of the epidermal growth factor receptor (
EGFR
) are the most commonly encountered mutations in patients with non-small cell ...lung cancer (NSCLC) and predict better clinical outcomes following treatment with EGFR-tyrosine kinase inhibitors (TKIs). The inflammatory indicator neutrophil-to-lymphocyte ratio (NLR) in peripheral blood serves as a predictive factor for NSCLC patients treated with chemotherapy. Here, we aimed to evaluate the correlation between NLR and clinical efficacy of EGFR-TKIs in NSCLC patients harboring
EGFR
mutations.
Methods
We retrospectively collected information of 205 patients with advanced NSCLC harboring exon 19 deletion or L858R point mutation and receiving gefitinib or erlotinib. The clinical outcomes in the NSCLC patients were evaluated based on NLR level before EGFR-TKI therapy.
Results
The optimal cut-off value for NLR was 3.55. The response rates in the low-NLR and high-NLR groups were 69.2% and 51.5%, respectively. The median progression-free survival (PFS) in the low-NLR and high-NLR groups were 15.7 months and 6.7 months, respectively. The median overall survival (OS) in the low-NLR and high-NLR groups were 37.6 months and 19.2 months, respectively. The multivariate analysis identified performance status (PS), NLR, stage, and smoking status as independent predictors of PFS. Moreover, the PS and NLR were identified as independent predictors of OS.
Conclusions
NLR was a significant predictor of clinical efficacy and OS in NSCLC patients harboring
EGFR
mutations treated with gefitinib or erlotinib.
Platinum-based adjuvant chemotherapy after complete resection has become a standard treatment for patients with stage II to IIIA non-small cell lung cancer; however, not all patients exhibit survival ...benefits. Therefore, the development of predictive biomarkers for selecting a subgroup of patients who may show improved survival after these treatments is important. Among the 42 proteins identified here using a proteomics analysis that were recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma who received platinum-based adjuvant chemotherapy, the tumor necrosis factor-receptor-associated protein 1 (TRAP1) was detected in patients with a short disease-free survival. TRAP1 expression was immunohistochemically analyzed in 64 patients with completely resected stage II and IIIA lung adenocarcinoma treated with platinum-based adjuvant chemotherapy. TRAP1 expression was significantly associated with higher p-TNM stage (P = 0.005) and lymph node metastasis (P = 0.017). Moreover, TRAP1 expression was significantly correlated with a shorter disease-free survival (P = 0.028). Furthermore, TRAP1-siRNA-treated LC-2/ad cells derived from lung adenocarcinoma exhibited significantly reduced proliferation and increased sensitivity to cisplatin. These results suggest that TRAP1 expression is a valuable biomarker for predicting the poor survival of platinum-based adjuvant chemotherapy in patients with resected lung adenocarcinoma.
Small cell lung cancer (SCLC) is characterized by a high propensity for metastases and a poor prognosis irrespective of high sensitivity for initial chemotherapy. Although interstitial pneumonia (IP) ...is one of risk factors for lung cancer, efficacy of cytotoxic chemotherapy for patients with SCLC with IP remains unclear. Our study aims to evaluate the efficacy of systemic chemotherapy and assess risk of acute exacerbation (AE)-IP with cytotoxic drugs for extensive disease (ED)-SCLC patients with IP.
We performed a retrospective study of 192 consecutive ED-SCLC patients with IP (n = 40) and without IP (n = 152) between 2008 and 2016.
31 of 40 ED-SCLC patients with IP and 130 of 152 patients without IP received systemic chemotherapy. The efficacy of chemotherapy in patients with IP was not inferior to that in patients without IP (overall survival OS, 7.1 95% confidence interval (CI): 0.2-14.0 vs. 10.0 95% CI: 8.2-11.8 months, P = 0.57). Pretreatment serum levels of lactate dehydrogenase (LDH; 651.7 ± 481.0 vs. 301.4 ± 110.7 U/mL, P = 0.01) and C-reactive protein (CRP; 8.9 ± 9.6 vs. 1.8 ± 1.8 U/mL, P = 0.008) were correlated with developed AE-IP in the ED-SCLC patients with IP.
Systemic chemotherapy was effective even in ED-SCLC patients with IP. However, the risk of developed AE-IP that was high in patients with IP and should be evaluated using serum LDH and CRP levels before initial chemotherapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Introduction
Afatinib is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring common
EGFR
mutations; however, the clinicopathological factors that predict this ...drug’s effectiveness in real-world settings remain unclear. We therefore evaluated the effectiveness of afatinib in such patients and assessed potential prognostic factors.
Methods
We retrospectively investigated patients with NSCLC who received first-line afatinib between July 2014 and August 2018. Variables (including sex, age, performance status, neutrophil-to-lymphocyte ratio,
EGFR
genotype, smoking status, clinical stage prior to treatment stage IV vs.. postoperative recurrence, presence or absence of brain metastases, body surface area, any afatinib dose reductions, and afatinib starting dose 40 vs.. 20 or 30 mg) were subjected to a Cox proportional hazards regression model to estimate progression-free survival (PFS).
Results
Forty-eight patients with a median age of 67 years were included; the objective response rate was 62.5% (30 patients). The median PFS was 14.1 months; the PFS periods were 11.8 and 15.9 months for patients receiving 40 mg versus 20–30 mg of afatinib (
P
= 0.41), respectively, and were 14.5 and 13.8 months for patients who required afatinib dose reduction and those who did not, respectively (
P
= 0.80). The PFS tended to be longer in patients without brain metastases (albeit not significantly). Ultimately, no significant predictive values for PFS were identified.
Conclusions
Afatinib is effective for patients with NSCLC harboring common
EGFR
mutations irrespective of their clinicopathological backgrounds. A direct comparison of afatinib and osimertinib in treatment-naïve patients is warranted to determine the optimal standard of care.
We herein report the case of a 52-year-old man with stage IV lung adenocarcinoma. The patient was negative for epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated ...protein-like 4 (EML4) /anaplastic lymphoma kinase (ALK) rearrangement. He was treated with nivolumab as a third-line chemotherapy. After four cycles of nivolumab treatment, a partial response was observed in the brain and at the primary tumor site. Nivolumab treatment has been continued for 11 months without progression. Immunohistochemistry revealed that the programmed death-ligand 1 (PD-L1) expression was 0% (according to the tumor proportion score). Our case indicates that the efficacy of programmed cell death 1 inhibitors is not solely predicted by the PD-L1 status, and that immune checkpoint inhibitors might be effective for the treatment of central nervous system metastasis.
Background
Galectin‐3 (GAL3), a protein encoded by the LGALS3 gene, plays diverse roles in cancer initiation, progression, and drug resistance. Accordingly, high GAL3 expression in tumor cells is ...associated with poor prognosis in non‐small cell lung cancer (NSCLC). However, the prognostic impact of GAL3 expression on patients with resected NSCLC receiving platinum‐based adjuvant chemotherapy (AC) remains unclear.
This study aimed to determine the prognostic significance of GAL3 expression in NSCLC patients receiving platinum‐based AC.
Methods
The study included 111 patients with completely resected stages II and IIIA NSCLC who were receiving platinum‐based AC. GAL3 expression in cancer cells was evaluated immunohistochemically according to H‐score (“histo score), with a score of ≥170 considered as high expression. The correlation of GAL3 expression with clinicopathological characteristics and survival was subsequently evaluated.
Results
In survival analysis, GAL3 expression was significantly associated with recurrence‐free survival (RFS) and overall survival (OS). In multivariate analysis, GAL3 expression was an independent predictive factor of RFS rather than OS.
Conclusions
GAL3 expression is a reliable biomarker to predict the prognosis of completely resected NSCLC patients receiving platinum‐based AC.
High galectin‐3 expression is associated with poor prognosis in patients with NSCLC. Thus, galectin‐3 expression is a reliable marker in predicting clinical outcomes in patients with completely resected NSCLC treated with platinum‐based adjuvant chemotherapy. This study provides a further understanding of the tumorigenesis and biology of NSCLC, which might be useful in detecting novel prognostic markers or therapeutic targets in completely resected stages II and IIIA NSCLC receiving platinum‐based AC for improving survival outcomes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Osimertinib is recommended for non‐small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such ...patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M‐positive advanced NSCLC who progress on prior EGFR‐tyrosine kinase inhibitors (TKIs).
Methods
We conducted a prospective observational cohort study. Median BSA and BMI were used as cut‐off values to evaluate the impact of body size variables on osimertinib chemotherapy.
Results
The median BSA and BMI of 47 patients were 1.50 m2 and 21.5 kg/m2, respectively. Clinical outcomes did not significantly differ between the high and low BSA groups, with response rates of 59.1% and 56.0% (P = 0.83) and progression‐free survival (PFS) of 7.6 and 9.1 months (P = 0.69), respectively. Similarly, there were no significant differences between the high and low BMI groups relative to response rates, which were 60.8% and 54.1% (P = 0.64), respectively, and PFS, which was 7.6 months in both groups (P = 0.38). No significant differences were observed among toxicity profiles in relation to BSA or BMI. Multivariate analysis identified better performance status, young age, and EGFR exon 19 deletion as independent favorable predictors of PFS.
Conclusion
The efficacy of osimertinib does not significantly vary relative to body size variables of patients with T790M‐positive NSCLC who progress on prior EGFR‐TKIs.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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