Anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancers can be effectively treated with an ALK tyrosine kinase inhibitor (TKI) such as crizotinib, but the response ...magnitude and duration are heterogeneous. Several ALK variants have been identified, but few studies have focused on the effects of different ALK variants on the efficacy of crizotinib.
Among 55 patients treated with crizotinib as the initial ALK-TKI between January 2007 and December 2014, we identified 35 patients with tumor specimens that could be evaluated for ALK variants by reverse transcription polymerase chain reaction. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate and progression-free survival (PFS) according to the ALK variants.
The most frequent ALK variant was variant 1 in 19 patients (54%), followed by variant 2 in five patients (14%), variant 3a/3b in four patients (12%), and other variants in seven patients (20%). Objective response rate was 69% in all patients, whereas it was 74% and 63% in the variant 1 and non-variant 1 groups, respectively. The median PFS time was significantly longer in patients with variant 1 than in those with non-variant 1 (median PFS, 11.0 months 95% CI, 6.5 to 43.0 months v 4.2 months 95% CI, 1.6 to 10.2 months, respectively; P < .05). Multivariable analysis identified two significant factors associated with PFS duration, ALK variant 1 (hazard ratio, 0.350; 95% CI, 0.128 to 0.929; P < .05) and advanced stage (hazard ratio, 4.646; 95% CI, 1.381 to 21.750; P < .05).
Our results indicate the better efficacy of crizotinib in patients with ALK variant 1 versus non-variant 1. The ALK variant status might affect the efficacy of ALK-TKIs.
Background
We aimed to analyze the feasibility and risk factors associated with early mobilization (EM) within 4 h after thoracoscopic lobectomy and segmentectomy.
Methods
This study retrospectively ...evaluated 214 consecutive patients who underwent thoracoscopic anatomical pulmonary resection using our EM protocol between October 2017 and February 2019. We compared the correlations of the patients’ characteristics including the total number of drugs and perioperative parameters such as air leak, and orthostatic hypotension (OH) between the EM (E group) and failed EM (F group) groups. Second, we evaluated risk factors for OH, which often causes critical complications.
Results
A total of 198 patients (92.5%: E group) completed the EM protocol, whereas 16 patients did not (7.5%: F group). The primary causes of failure were severe pain, air leak, postoperative nausea and vomiting, and OH (
n
= 1, 3, 8, and 4). Upon univariate analysis, air leakage, OH, and non-hypertension were identified as risk factors for failed EM (all
p
<0.05). EM was associated with a shortened chest tube drainage period (
p
<0.01). Thirty patients (14%) experienced OH, and 20% of them failed EM. A total number of drugs ≥5 (
p
= 0.015) was an independent risk factor for OH. Operative and anesthetic variables were not associated with EM or OH.
Conclusions
The EM protocol was safe and useful for tubeless management. Surgeons should be advised to actively prevent air leak. Our EM protocol achieved a low frequency of OH in mobilization. Due to its versatility, our mobilization protocol may be promising, especially in patients without severe comorbidities.
Clinical registration number
: The study protocol was approved by the Review Board of Aichi Cancer Center (approval number: 2020-1-067).
Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop ...progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option.
This study showed the efficacy of local therapy for oligoprogressive disease after PD‐1 blockade in advanced non‐small‐cell lung cancer.
Programmed death-ligand 1 (PD-L1) expression is a predictor of immune checkpoint inhibitor (ICI) treatment efficacy. The clinical efficacy of ICIs for non-small-cell lung cancer (NSCLC) patients ...harboring major mutations, such as
or
mutations, is limited. We genotyped 190 patients with advanced lung adenocarcinomas who received nivolumab or pembrolizumab monotherapy, and examined the efficacy in NSCLC patients with or without major mutations. Among the patients enrolled in the genotyping study, 47 patients harbored
mutations, 25 patients had
mutations, 5 patients had a
mutation, 6 patients had a
mutation, and 7 patients had
rearrangement. The status of PD-L1 expression was evaluated in 151 patients, and the rate of high PD-L1 expression (≥50%) was significantly higher in patients with
mutations. The progression-free survival was 0.6 (95% CI: 0.2-2.1) months for
-positive patients and 1.8 (95% CI: 1.2-2.1) months for
-positive patients. All patients with
rearrangement showed disease progression within three months from the initiation of anti-PD-1 treatment. Our data suggested that ICI treatment was significantly less efficacious in patients with
rearrangement than in patients with
mutations, and PD-L1 expression was not a critical biomarker for ICI treatment for patients with one of these mutations.
Nivolumab offers a superior survival benefit over docetaxel in patients with advanced, previously treated non-small-cell lung cancer (NSCLC). An association between programmed cell death ligand-1 ...(PD-L1) expression and the efficacy of nivolumab has been reported in many studies. However, the association between the clinical parameters and efficacy of nivolumab remains unclear in advanced NSCLC patients.
Among 124 patients, 108 (88%) were performance status (PS) 0 to 1. PD-L1 expression was assessed in 89 patients, with 51 (57%) patients having PD-L1 positive expression. In all patients, the objective response rate (ORR) in patients with elevated CRP levels (≥ 1 mg/dl) was significantly worse than those without elevated CRP levels (< 1 mg/dl) (8.3 vs 23.4%,
= 0.0180). The PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) were significantly associated with a shorter PFS and OS in patients treated with nivolumab. Multivariate analyses showed that the PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) and PD-L1 expression were significant factors associated with a longer PFS of nivolumab.
We retrospectively analyzed 124 patients who received nivolumab as a subsequent treatment. The patient characteristics, laboratory data at baseline (C-reactive protein CRP and lactate dehydrogenase LDH), PD-L1 expression, nivolumab response, progression-free survival (PFS), and overall survival (OS) were evaluated.
Clinical parameters, such as PS, serum CRP, serum LDH, and smoking status, were significantly associated with the response duration and survival in patients treated with nivolumab.
Immunological parameters and nutritional status influence the outcome of patients with malignant tumors. A prognostic nutritional index, calculated using serum albumin levels and peripheral ...lymphocyte count, has been used to assess prognosis for various cancers. This study aimed to investigate whether this prognostic nutritional index affects overall survival and the incidence of postoperative complications in patients with completely resected non-small cell lung cancer.
We retrospectively reviewed the medical records of 409 patients with non-small cell lung cancer who underwent complete resection between 2005 and 2007 at the Aichi Cancer Center.
The 5-year survival rates of patients with high (≥50) and low (<50) prognostic nutritional indices were 84.4% and 70.7%, respectively (p = 0.0011). Univariate analysis showed that gender, histology, pathological stage, smoking history, serum carcinoembryonic antigen levels, and prognostic nutritional index were significant prognostic factors. Multivariate analysis identified pathological stage and the prognostic nutritional index as independent prognostic factors. The frequency of postoperative complications tended to be higher in patients with a low prognostic nutritional index.
The prognostic nutritional index is an independent prognostic factor for survival of patients with completely resected non-small cell lung cancer.
The differences in biological characteristics among different genotypes of classical EGFR mutations have not been clarified. This study aimed to clarify the clinical and biological differences ...between L858R and 19 deletion in NSCLC.
We analyzed a cohort of 191 consecutive cases of surgically resected NSCLC harboring EGFR driver mutations (L858R or 19 deletion) in which curative resection was performed in Aichi Cancer Center Hospital, Nagoya, Japan, from January 2006 to September 2021 and in which recurrence subsequently developed. We also subjected 61 surgically resected NSCLC specimens harboring EGFR driver mutations (L858R or 19 deletion) to an RNA sequencing analysis.
In patients with stage I disease, the median time to recurrence did not differ to a statistically significant extent between the types of EGFR mutations; however, among those with stage II and III disease, the median time to recurrence in patients with the L858R genotype tended to be shorter in comparison to those with 19 deletion (log-rank test, p = 0.47 and 0.46, respectively). In comparison to 19 deletion tumors, L858R tumors had higher cytological malignancy (e.g., mitotic ability) and showed stronger immunogenicity.
L858R and 19 deletion tumors are likely to have a slight difference in the time to recurrence. They suggest that even in EGFR driver tumors, which are treated as the same disease category, the biological characteristics of the tumors are different, which may leave room for innovations in postoperative treatment and treatment at recurrence.
Panel-based next-generation sequencing (NGS) has been carried out in daily clinical settings for the diagnosis and treatment guidance of patients with non-small cell lung cancer (NSCLC). The success ...of genomic tests including NGS depends in large part on preparing better-quality DNA or RNA; however, there are no established operating methods for preparing genomic DNA and RNA samples.
We compared the following two quantitative methods, the QubitTM and NanoDropTM, using 585 surgical specimens, 278 biopsy specimens, and 82 cell block specimens of lung cancer that were used for genetic tests, including NGS. We analyzed the success rate of the genomic tests, including NGS, which were performed with DNA and RNA with concentrations that were outliers for the Qubit Fluorometer.
The absolute value for DNA concentrations had a tendency to be higher when measured with NanoDropTM regardless of the type of specimen; however, this was not the case for RNA. The success rate of DNA-based genomic tests using specimens with a concentration below the lower limit of QubitTM detection was as high as approximately 96%. At less than 60%, the success rate of RNA-based genomic tests, including RT-PCR, was not as satisfactory. The success rates of the AmpliSeqTM DNA panel sequencing and RNA panel sequencing were 77.8% and 91.5%, respectively. If at least one PCR amplification product could be obtained, then all RNA-based sequencing was performed successfully.
The concentration measurements with NanoDropTM are reliable. The success rate of NGS with samples at concentrations below the limit of detection of QubitTM was relatively higher than expected, and it is worth performing PCR-based panel sequencing, especially in cases where re-biopsy cannot be performed.
Purpose
This study investigated whether the divided method of multi-level intercostal nerve block (ML-ICB) could reduce the ropivacaine dose required during thoracoscopic pulmonary resection, while ...maintaining the resting postoperative pain scores.
Methods
This retrospective, single-cohort study enrolled 241 patients who underwent thoracoscopic pulmonary resection for malignant tumors between October 2020 and March 2022 at a cancer hospital in Japan. ML-ICB was performed by surgeons under direct vision. The differences in intraoperative anesthetic use and postoperative pain-related variables at the beginning and end of surgery between group A (single-shot ML-ICB; 0.75% ropivacaine, 20 mL at the end of the surgery) and group B (divided ML-ICB, performed at the beginning and end of surgery; 0.25% ropivacaine, 30 mL total) were assessed. The numerical rating scale (NRS) was used to evaluate pain 1 h and 24 h postoperatively.
Results
Intraoperative remifentanil use was significantly lower in group B (14.4 ± 6.4 μg/kg/h) than in group A (16.7 ± 8.4 μg/kg/h) (
P
= 0.02). The proportion of patients with NRS scores of 0 to 3 at 24 h was significantly higher in group B (85.4%, 106/124) than in group A (73.5%, 86/117) (
P
= 0.02). The proportion of patients not requiring postoperative intravenous rescue drugs was significantly higher in group B (78.2%, 97/124) than in group A (61.5%, 72/117) (
P
< 0.01).
Conclusion
The divided method of ML-ICB could reduce the intraoperative remifentanil dose, decrease the postoperative pain score at 24 h, and curtail postoperative intravenous rescue drug use, despite using half the total ropivacaine dose intraoperatively.
•Prognostic difference between the T2a-PL1 and T2a-PL2 tumor groups was significant.•T2a-PL2 group could be categorized into a worse prognostic category (T2b).•T3-PL3 tumors involving neighboring ...organs could also be subcategorized.•Subcategorization of pleura infiltration (T3a) and others (T3b) could be practical.•These information could complement the TNM classification of lung cancer.
The eighth tumor-node-metastasis (TNM) classification system for lung cancer has been used since January 2017 and must be applied to an individual institution’s database.
We analyzed pathological stage data of 2756 patients who underwent resection of non–small-cell lung cancer, particularly in terms of the degree of visceral pleural invasion and involved neighboring structures.
Few patients had stage IIA disease (103, 4%); stratification between stages IB and IIA was insufficient (p = 0.129). When T2a tumors were divided into PL1 and PL2 subgroups based on the degree of pleural invasion, there was a significant prognostic difference between the subgroups (p < 0.001). By incorporating T2a tumors with PL2 (T2a-PL2) into the T2b category, modified stages IB, IIA (234, 8%), and IIB were well stratified (IB vs. IIA, p < 0.001; IIA vs. IIB, p = 0.011). Focusing on T3 tumors with PL3 (T3-PL3) invading neighboring structures, multivariate analysis for surveying pT3N0-2M0 tumors revealed that completeness of resection (p = 0.002), implementation of any postoperative therapies (p = 0.003), and subcategorization of whether only the pleura was infiltrated or other deeper structures were also invaded (p = 0.024) were significant and crucial predictors. N2 disease showed worse outcome than N0-1 diseases, with marginal difference (p = 0.054).
T2a-PL2 tumors could be categorized into a worse prognostic T2b category. For T3-PL3 tumors involving resectable neighboring organs, subcategorization of whether there is only pleura infiltration (T3a) or other deeper structure invasion (T3b) could be a practical consideration.
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