To evaluate the efficacy of pemetrexed plus cisplatin versus vinorelbine plus cisplatin as postoperative adjuvant chemotherapy in patients with pathologic stage II-IIIA nonsquamous non-small-cell ...lung cancer (NSCLC).
We performed a randomized, open-label, phase III study at 50 institutions within 7 clinical study groups in Japan. Patients with completely resected pathologic stage II-IIIA (TNM 7th edition) nonsquamous NSCLC were randomly assigned to receive either pemetrexed (500 mg/m
, day 1) plus cisplatin (75 mg/m
, day 1) or vinorelbine (25 mg/m
, days 1 and 8) plus cisplatin (80 mg/m
, day 1) with stratification by sex, age, pathologic stage,
mutation, and institution. These treatments were planned to be given every 3 weeks for 4 cycles. The primary end point was recurrence-free survival in the modified intent-to-treat population, excluding ineligible patients.
Between March 2012 and August 2016, 804 patients were enrolled (402 assigned to vinorelbine plus cisplatin and 402 assigned to pemetrexed plus cisplatin). Of 784 eligible patients, 410 (52%) had stage IIIA disease and 192 (24%) had
-sensitive mutations. At a median follow-up of 45.2 months, median recurrence-free survival was 37.3 months for vinorelbine plus cisplatin and 38.9 months for pemetrexed plus cisplatin, with a hazard ratio of 0.98 (95% CI, 0.81 to 1.20; 1-sided
= .474). Grade 3-4 toxicities reported more frequently for vinorelbine plus cisplatin than for pemetrexed plus cisplatin were febrile neutropenia (11.6%
0.3%, respectively), neutropenia (81.1%
22.7%, respectively), and anemia (9.3%
2.8%, respectively). One treatment-related death occurred in each arm.
Although this study failed to show the superiority of pemetrexed plus cisplatin for patients with resected nonsquamous NSCLC, this regimen showed a better tolerability as adjuvant chemotherapy.
Background
To examine the effects of postoperative adjuvant chemotherapy for elderly (
≥
75 years of age) patients with completely resected non-small cell lung cancer (NSCLC), we conducted a ...multi-institutional and prospective observational study.
Methods
Patients were recruited between January 2014 and December 2017, and assigned to two cohort groups based on the patients’ choice either to receive postoperative adjuvant chemotherapy (Cohort B) or not (Cohort A). All the patients were observed for 2 years after enrollment. The primary endpoint was the postoperative change of Karnofsky Performance Status (KPS) at 2 years. The secondary endpoints were postoperative recurrence-free survival (RFS) and overall survival (OS) at 2 years, and the completion rate of the adjuvant chemotherapy.
Results
Two hundred and seventy-two patients were enrolled (Cohort A,
n
= 225; Cohort B,
n
= 47). At any time point after surgery, no marked difference of KPS was observed between Cohort B and Cohort A. The RFS at 2 years was 70.8% (95% confidence interval CI, 64.3–76.4) in Cohort A and 76.0% (95% CI 60.8–85.9) in Cohort B. The OS at 2 years was 85.9% (95% CI 80.4–89.9) in Cohort A and 89.1% (95% CI 75.8–95.3) in Cohort B. The completion rate of planned chemotherapy was 49.9% (95% CI 34.1–63.9%).
Conclusions
The elderly patients were not likely to choose to receive postoperative adjuvant chemotherapy; however, no significant adverse effect on postoperative KPS was identified.
Trial registration
Clinical Trial Registration ID: UMIN000020736.
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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
Red cell distribution width (RDW) to platelet ratio (RPR) is a prognosticator in acute pancreatitis and myocardial infarction; however, the prognostic values of RDW and RPR in breast cancer have not ...been studied. This retrospective analysis of 299 breast cancer patients investigated the association between RDW and RPR and clinicopathological characteristics and prognosis, compared to platelet distribution width to platelet count ratio (PDW/P) which is a known independent prognostic factor in patients with breast cancer. We found a significant correlation between RPR, and age and HER2 status. An elevated RPR significantly correlated with age and HER2 status. After a median follow-up duration of 48 months, tumour size, nuclear grade, PDW/P, and RPR were recgnized to be significantly associated with lower disease-free survival rates (tumour size: p < 0.01; nuclear grade, PDW/P, and RPR: p < 0.05) in univariate analysis. Tumour size and RPR were significant prognostic factors for lower disease-free survival rates, with hazard ratios of 4.31 (95% confidence interval: 1.76-10.53) (p < 0.01) and 2.79 95% confidence interval: 1.01-87.69) (p < 0.05), respectively, in a multivariate analysis using the Cox proportional hazards model. This is the first study showing that an elevated RPR could independently predict poor prognosis in patients with breast carcinoma. Thus, RPR could be a novel biomarker for prognostic estimation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Activated platelets promote tumor cell growth, angiogenesis, and invasion. Platelet activity can be inferred by platelet volume indices (PVIs), which include platelet distribution width (PDW), mean ...platelet volume (MPV), platelet distribution width-to-platelet count ratio (PDW/P), and mean platelet volume-to-platelet count ratio. Platelets and platelet-related markers, such as the platelet-to-lymphocyte ratio, have been found to be significant prognostic factors in patients with breast cancer. However, the role of PVIs for predicting survival in breast cancer remains unknown; hence, we performed this retrospective analysis of 275 patients with breast cancer. PVIs were compared with clinicopathological variables, and were assessed to identify independent indicators associated with disease-free survival (DFS) using the Cox proportional hazards model. An elevated PDW/P significantly correlated with age and HER2 status. Univariate analysis revealed that elevated PDW, MPV, and PDW/P as well as tumor size, nuclear grade, and lymph node involvement were significantly associated with inferior DFS rates (tumor size: p<0.01; nuclear grade, lymph node involvement, PDW, MPV, and PDW/P: p<0.05). On multivariate analysis, a large tumor size and elevated PDW/P were significant prognostic factors for DFS, with hazard ratios of 3.24 (95% confidence interval CI: 1.24-8.47) and 2.99 (95% CI: 1.18-7.57), respectively (p<0.05). Our study is the first to reveal that an elevated PDW/P significantly reduces DFS in patients with breast carcinoma. Measuring the PDW/P is simple, relatively inexpensive, and almost universally available using routine blood counts; this makes it an attractive biomarker for improved risk assessment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to conduct a detailed anatomical examination of the arterial supply to level Ib lymph nodes corresponding to mammary sentinel lymph nodes. This was achieved by focusing on the ...relationship with course changes of the axillary artery trunk using 41 cadavers (49 axillae). The course patterns of the axillary artery were classified as: “Standard type,” which penetrate the brachial plexus (occurrence rate, 51%); “Superficial brachial artery type,” which ran along the superficial layer of the brachial plexus (2%); “Superficial subscapular artery (SSbsA) type,” which entered the deep layer without penetrating the brachial plexus (42.9%); and others (4.1%). The lateral thoracic artery, thoracodorsal artery, inferior pectoral artery, and superficial thoracic artery were distributed in a regular pair relationship according to each running type of the axillary artery for the Ib lymph nodes. Comparing blood supply ratio to the Ib lymph nodes, using SSbsA occurrence as a reference, showed that significant differences were observed with the inferior pectoral artery control for the standard subscapular artery group and the lateral thoracic artery control for the SSbsA group (
p
< 0.0001). It was suggested that in selective modeling of vascular networks during upper limb developments, two formation tendencies occur. The standard axillary and SSbsA axillary artery trunks are induced when the inferior pectoral artery-derived feeding arteries in the superficial brachial artery system are selected for Ib lymph nodes, or lateral thoracic artery-derived feeding arteries, which are closely related to the SSbsA pathway, are acquired.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose: Robot-assisted thoracic surgery (RATS) has become popular because of its minimally invasive nature and reduced burden on surgeons. The anterior approach (AA) is beneficial because it ...utilizes the same field of view and procedures as thoracotomy and video-assisted thoracic surgery, although the disadvantages are less well-known.Methods: We retrospectively examined 35 consecutive patients who underwent RATS lobectomy via the AA, focusing on clinical factors and postoperative complications.Results: The study included 12 males and 23 females with a median console time of 177 (120–346) min, median blood loss of 0 (0–100) mL, and median stapler usage of 5 (2–10) units. Postoperative complications, classified as Clavien–Dindo grade ≥III, included three cases of grade IIIa (prolonged air leakage) and one case each of grade IIIb and grade IVa (middle lobe torsion and ventricular arrhythmia). The influence of stapling device operation cannot be ruled out in prolonged air leakage and middle lobe torsion. A moderate correlation (correlation coefficient = 0.492, p = 0.003) was observed between console time and the number of staplers used.Conclusion: Although no severe incidence of vascular injury was observed with the AA, complications related to the use of stapling devices were noted.
Abstract Background Some types of somatic mutation of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) are associated with a significant clinical response to a ...tyrosine kinase inhibitor (TKI). However, most of the patients with this type of sensitive mutations in their tumor show acquired resistance during the TKI treatment. Methods The mutations in exons 19–21 of the EGFR gene were examined in both the pre-treatment and the post-treatment gefitinib resistant tumors in 10 patients with lung adenocarcinoma. Eight patients were recurrent cases after surgery, and two patients were non-surgical cases whose tumor specimens were obtained from the metastatic lymph node and endobronchially invading tumor. Results In 10 patients, 5 patients had a deletion in exon 19 and another 5 did L858R mutation in exon 21 of EGFR in gefitinib pre-treatment tumors. The mutation status did not change in the gefitinib-resistant tumors. In 7 of 10 patients, the gefitinib-resistant tumors had a secondary T790M mutation, which was not detected in the gefitinib pre-treatment tumors. In one patient, only one of the 4 gefitinib-resistant tumors showed the T790M mutation. Neither other novel secondary mutations of EGFR nor the K-ras were observed in their gefitinib-resistant tumors. Neither MET gene amplification nor HGF were observed in their gefitinib-resistant tumors without T790M mutation. Conclusions The T790M mutation in the EGFR is relatively common in the patients with acquired resistance to gefitinib. However, mechanisms other than T790M, MET, and HGF status are involved in resistance to gefitinib.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Adenocarcinoma of the lung unrelated to a smoking habit occurs more frequently in women than men, thus suggesting an association between female hormones and development of these tumors. The aim of ...this study was to elucidate the correlation between expression of estrogen receptor (ER) and clinicopathologic factors, including a mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR), and prognosis in adenocarcinoma of the lung.
This study evaluated 447 resected primary lung adenocarcinoma specimens. The expression of ERalpha and ERbeta was evaluated with an immunohistochemical method. The EGFR mutation was evaluated with polymerase chain reaction.
A strong cytoplasmic expression of ERalpha and nuclear expression of ERbeta were detected in 49.4% and 48.5% of all patients, respectively. A strong nuclear expression of ERbeta was independently associated with the EGFR mutations (odds ratio = 2.947; 95% CI, 1.97 to 4.57; P < .001) and good differentiation (odds ratio = 1.84; 95% CI, 1.21 to 2.80; P = .004) and was correlated with an increasing disease-free survival in patients with EGFR mutations (hazard ratio = 2.18; 95% CI, 1.18 to 4.06; P = .014). However, no prognostic significance was identified in patients without EGFR mutations. No clinicopathologic and/or prognostic significance of a strong expression of cytoplasmic ERalpha was found.
A strong nuclear expression of ERbeta correlates with EGFR mutations, and its favorable prognostic significance was influenced by the EGFR mutations in adenocarcinoma of the lung.
Ciliated muconodular papillary tumor (CMPT) of the lung is characterized as a peripheral low-grade malignant tumor with ciliated columnar cells and goblet cells with basaloid cell proliferation. ...Herein, we report on a case of CMPT with a radiologically abnormal shadow which was reminiscent of adenocarcinoma. The patient underwent right S6 + S8a segmentectomy because an intraoperative biopsy suggested CMPT, the malignancy of which was difficult to distinguish; however, the tumor was small and located in the peripheral lung. Many details of this tumor remain unclear, as CMPT is a rare tumor with few reports. CMPT has therefore not yet been classified by the WHO. In this report, we will consider the characteristics of CMPT and treatment based on our case and previous case reports.
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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
Objective
Lung cancer patients with interstitial lung diseases (ILDs) who have undergone pulmonary resection often develop acute exacerbation of interstitial pneumonia (AE) in the post-operative ...period. To predict who is at high risk of AE, we propose a scoring system that evaluates the risk of AE in lung cancer patients with ILDs.
Methods
We derived a score for 30-day risk of AE onset after pulmonary resection in lung cancer patients with ILDs (
n
= 1,022; outcome: risk of AE) based on seven risk factors for AE that were identified in a previous retrospective multi-institutional cohort study. A logistic regression model was employed to develop a risk prediction model for AE.
Results
A risk score (RS) was derived: 5 × (history of AE) + 4 × (surgical procedures) + 4 × (UIP appearance in CT scan) + 3 × (male sex) + 3 × (preoperative steroid use) + 2 × (elevated serum sialylated carbohydrate antigen, KL-6 level) + 1 × (low vital capacity). The RS was shown to be moderately discriminatory with a c-index of 0.709 and accurate with the Hosmer–Lemeshow goodness-of-fit test (
p
= 0.907). The patients were classified into three groups: low risk (RS: 0–10; predicted probability <0.1;
n
= 439), intermediate risk (RS: 11–14; predicted probability 0.1–0.25;
n
= 559), and high risk (RS: 15–22; predicted probability >0.25;
n
= 24).
Conclusion
Although further validation and refinement are needed, the risk score can be used in routine clinical practice to identify high risk individuals and to select proper treatment strategies.
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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
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