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1.
Anticancer Res ; 41(12): 6237-6246, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34848479

RESUMO

BACKGROUND/AIM: Surgical stress significantly decreases serum diamine oxidase (DAO), a marker of intestinal mucosal maturation and integrity. This study aimed to determine the effects of postoperative enteral and total parenteral nutrition (EN and TPN, respectively) in patients with esophageal cancer. PATIENTS AND METHODS: This prospective randomized trial compared serum DAO activities, nutritional states, trace elements and complications between patients who underwent esophagectomy and received EN or TPN for seven days thereafter. RESULTS: Fifty-one patients were randomized to receive EN or TPN. The rates of change in serum DAO activity from the day before surgery were 0.79, 0.89 and 0.91 on postoperative days (POD) 1, 3 and 7, respectively, in the EN group, and 0.64, 0.76 and 1.06, respectively, in the TPN group, with no significant differences. Furthermore, the rates of changes in indicators of nutritional status, namely total protein, albumin, total cholesterol, trace element concentrations and infectious and non-infectious complications did not significantly differ between the groups. CONCLUSION: EN and/or TPN can be administered for early nutritional management until resumption of oral intake after esophagectomy according to the postoperative status of individual patients with esophageal cancer.

2.
J Clin Oncol ; : JCO2101729, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726958

RESUMO

PURPOSE: To investigate the efficacy of gefitinib as an adjuvant therapy for non-small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS: IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non-small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS: Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION: Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.

3.
J Clin Oncol ; : JCO2101315, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793245

RESUMO

PURPOSE: We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone. PATIENTS AND METHODS: Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, -10% for the difference in the overall CR rate). RESULTS: Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] v FosAPR [N = 393]) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, -2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% (P < .001) and 0.3% versus 3.6% (P < .001), respectively. CONCLUSION: FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.

4.
Thorac Cancer ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34643053

RESUMO

INTRODUCTION: Tumor size is an absolute recurrence risk in lung cancer. Although morphological features also reflect recurrence risk, its significance among lower-risk cases characterized by small size is unknown. We aimed to evaluate the relationship between pathological invasive tumor size and morphological features, and their prognostic impact by considering them simultaneously in lung adenocarcinoma. PATIENTS AND METHODS: We retrospectively reviewed 563 pN0M0 patients with pathological invasive size of ≤40 mm. The patients were classified by pathological invasive size and pathological malignant grading using the proportion of subhistological components. The prognostic impact was evaluated using recurrence-free survival (RFS) and overall survival (OS). The impact on prognosis was evaluated using uni- and multivariate analyses. RESULTS: The proportion of histological grade changed according to invasive tumor size. Patients with high malignant grade (G3) showed worse RFS than those with low and intermediate malignant grade (G1+2) with invasive size ≤20 mm. The 5-year RFS (G1+2 vs. G3) in 5-10 mm was 96.0% vs. 83.3% (HR = 5.505, 95% CI = 7.156-1850, p < 0.001) and in 10-20 mm was 87.8% vs. 67.1% (HR = 2.829, 95% CI = 4.160-43.14, p < 0.001). G3 patients were significantly bigger in invasive size and included more pleural/lymphatic/vascular invasion and recurrence. Multivariate analysis indicated pathological G3 status was significantly associated with worse RFS (HR = 2.097, 95% CI = 1.320-3.333, p = 0.002). CONCLUSIONS: Invasive tumor size and pathological malignant grade overlap in invasive adenocarcinoma. G3 patients are more likely to have pleural/lymphatic/vascular invasion and significantly worse RFS compared to G1/G2 cases, even with a small invasive size of ≤20 mm.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34647128

RESUMO

OBJECTIVES: Prognosis after segmentectomy for early-stage non-small cell lung cancer (NSCLC) with a high consolidation tumour ratio (CTR) and [18F]-fluoro-2-deoxy-D-glucose (FDG) accumulation on positron emission tomography/computed tomography is unclear. METHODS: Participants of this study were 465 patients who underwent lobectomy or segmentectomy for clinical N0 NSCLC presenting solid component predominant tumour (CTR >50%) with a whole size ≤3 cm. Accumulations of FDG on positron emission tomography/computed tomography scans were scored according to the Deauville criteria, a 5-point visual evaluating method (Deauville score). The correlations between Deauville score, prognosis, and procedures were analysed. RESULTS: Characteristics of pathological invasiveness, such as lymphatic invasion (P < 0.001), vascular invasion (P < 0.001) and pleural invasion (P < 0.001), and non-adenocarcinoma histologies (P < 0.001) were more common in patients with Deauville scores of 3-5. The cumulative incidence of recurrence (CIR) was higher in patients with Deauville scores of 3-5 (P < 0.001). The CIR after lobectomy and segmentectomy did not differ significantly among patients with Deauville scores of 1 or 2 (P = 0.598) or those with Deauville scores of 3-5 (P = 0.322). In the analysis of propensity score matched cohort, the CIR after lobectomy and segmentectomy did not differ significantly between patients with Deauville scores of 1 or 2 and Deauville scores of 3-5. CONCLUSIONS: Segmentectomy may be feasible for NSCLC with high CTR (>50%) and accumulation of FDG. This finding should be confirmed in larger prospective studies.

6.
Clin Lung Cancer ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34690079

RESUMO

INTRODUCTION: The prognostic significance of mediastinal lymph node dissection (MLND) in elderly patients with non-small cell lung cancer (NSCLC) remains unclear. This post hoc analysis of a nationwide multicenter cohort study (JACS1303) evaluated the prognostic significance of MLND in octogenarians with NSCLC. MATERIALS AND METHODS: We included 622 octogenarians with NSCLC who underwent lobectomy. The median follow-up duration was 41.1 months. We compared survival and perioperative outcomes between patients who did and did not undergo MLND. RESULTS: In total, 414 (67%) patients underwent MLND (ND2 group), whereas 208 (33%) did not undergo MLND (ND0-1 group). The disease stage was more advanced in the ND2 group than in the ND0-1 group. Disease-free survival was slightly greater in the ND0-1 group with marginal significance (P= .079). In the matched cohort (N = 228), which mainly consisted of patients with clinical stage I disease (96%), there was no significant difference between the 2 groups regarding overall and disease-free survival (P= .908 and P = .916, respectively). Operative time and blood loss were significantly lower in the ND0-1 group than in the ND2 group in the entire cohort (P< .001 and P = .050, respectively) and in the matched cohort (P = .003 and P= .046, respectively). CONCLUSION: Based on a nationwide prospective database, we found limited prognostic impact of MLND, suggesting that MLND can be omitted for octogenarians with early-stage NSCLC.

8.
JTO Clin Res Rep ; 2(2): 100126, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34589986

RESUMO

Introduction: The International Association for the Study of Lung Cancer proposed a new grading criteria for invasive adenocarcinoma. However, its utility has not been validated. Methods: Patients who underwent complete resection of lung adenocarcinoma were included in this study. Then, they were divided into the following three groups on the basis of the criteria recently proposed by the International Association for the Study of Lung Cancer: grade 1, lepidic predominant tumor, with less than 20% of high-grade patterns; grade 2, acinar or papillary predominant tumor, with less than 20% of high-grade patterns; and grade 3, any tumor with greater than or equal to 20% of high-grade patterns. Results: Recurrence-free survival (RFS) was significantly different among the proposed grades (p < 0.001). The RFS of patients upgrading from current grade 2 (papillary or acinar predominant tumor) to proposed grade 3 (5-y RFS, 65.2%) was significantly worse than that of patients with proposed grade 2 (77.1%, hazard ratio = 1.882, 95% confidence interval: 1.236-2.866) but not significantly different from that of patients with grade 3 in both the current (micropapillary or solid predominant tumor) and proposed criteria (53.2%, hazard ratio = 0.761, 95% confidence interval: 0.456-1.269). Among patients with pathologic stage 0 or I, RFS was well stratified by the new grading system (p < 0.001) but not among patients with stage II or III (p = 0.334). In the multivariable analysis, the new grading was not a predictive factor of RFS. Conclusions: Although the proposed grading system well stratified RFS in patients with pathologic stage 0 or I lung adenocarcinoma, there is room for improvement.

9.
JTO Clin Res Rep ; 2(3): 100135, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34589998

RESUMO

Introduction: We examined the long-term efficacy and safety of nivolumab, a human monoclonal antibody that inhibits interactions between the programmed cell death protein-1 receptor and its ligands (programmed death-ligand 1 and programmed death-ligand 2), in Japanese patients with malignant pleural mesothelioma (MPM). Methods: Japanese patients with previously treated MPM (one or two regimens) were enrolled in a single-arm, phase 2 study and received nivolumab intravenously 240 mg every 2 weeks until progressive disease or unacceptable toxicity. The primary end point was the centrally assessed objective response rate. Other end points included overall survival (OS), progression-free survival (PFS), treatment-related adverse events, and patient-reported outcomes (Lung Cancer Symptom Scale for mesothelioma and EuroQOL visual analog scale). Patient enrollment started on June 16, 2016. Here, we report 3-year follow-up data (cutoff date: November 12, 2019). Results: Thirty-four patients were enrolled. The centrally assessed objective response rate was previously reported (29.4%). The 2- and 3-year OS rates were 35.3% and 23.5%, respectively, and the corresponding PFS rates were 17.0% and 12.7%. Median OS and PFS were 17.3 and 5.9 months, respectively. Eight patients were alive at 3 years of follow-up. Nivolumab was well tolerated and no new safety signals were found. The patient-reported outcomes were maintained without marked deteriorations during the study. Conclusions: Our results reveal clinically relevant long-term efficacy and safety of nivolumab for the treatment of MPM.

10.
JTO Clin Res Rep ; 2(6): 100178, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34590026

RESUMO

Introduction: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study. Methods: The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest). Results: The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths. Conclusions: The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34419248

RESUMO

PURPOSE: Despite becoming the preferred surgical technique for malignant pleural mesothelioma, pleurectomy/decortication has received few prospective clinical trials. Therefore, the Japan Mesothelioma Interest Group conducted a prospective multi-institutional study to evaluate the feasibility of neoadjuvant chemotherapy followed by pleurectomy/decortication. METHODS: Patients with histologically confirmed, resectable malignant pleural mesothelioma underwent neoadjuvant chemotherapy comprising pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 for 3 cycles, followed by pleurectomy/decortication. The primary end point was macroscopic complete resection rate regardless of the surgical technique used. RESULTS: Among the 24 patients enrolled, 20 received neoadjuvant chemotherapy and 18 proceeded to surgery, all of whom achieved macroscopic complete resection. Pleurectomy/decortication was performed in 15 patients. The trial satisfied the primary end point, with a macroscopic complete resection rate of 90% (18/20, 95% confidence interval, 68.3-98.8). No treatment-related 30- and 90-day mortality occurred. The overall survival after 1 and 2 years and median overall survival after registration were 95.0% (95% confidence interval, 69.5-99.3), 70.0% (95% confidence interval, 45.1-85.3), and 3.45 years (95% confidence interval, 1.64 to not available), respectively. The cumulative incidence of progression after 1 and 2 years and median time to progression were 33.3% (95% confidence interval, 17.3-64.1), 61.1% (95% confidence interval, 42.3-88.3), and 1.71 years (95% confidence interval, 1.00-2.99), respectively. The best postoperative value for forced expiratory volume was 78.0% of preoperative values. CONCLUSIONS: Neoadjuvant chemotherapy followed by pleurectomy/decortication was feasible with acceptable survival and mortality/morbidity. Postoperative pulmonary function was approximately 80% of the preoperative pulmonary function.

13.
J Thorac Dis ; 13(7): 4083-4093, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34422338

RESUMO

Background: The nodal classification of lung cancer is determined by the anatomical location of metastatic lymph nodes (mLNs). However, prognosis can be heterogeneous at the same nodal stage, and the current classification system requires improvement. Therefore, we investigated the correlation between the number of mLNs and prognosis in patients with non-small cell lung cancer. Methods: Using a multicenter database in Japan, we retrospectively reviewed the records of patients who underwent complete resection for lung cancer between 2010 and 2016. Kaplan-Meier curves were used to determine recurrence-free and overall survival. Multivariate analyses were performed using the Cox proportional hazards model. Results: We included 1,567 patients in this study. We could show a statistically significant difference in recurrence-free survival between pN2 patients with 1 mLN and pN2 patients with ≥2 mLNs (P=0.016). Patients with a combination of pN1 (≥4 mLNs) plus pN2 (1 mLN) had a poorer prognosis than pN1 patients (1-3 mLNs) (P=0.061) and a better prognosis than pN2 patients (≥2 mLNs) patients (P=0.007). Multivariate analysis showed that the number of mLNs was independently associated with cancer recurrence in patients with pN1 and pN2 disease (P=0.034 and 0.018, respectively). Conclusions: Nodal classification that combines anatomical location and the number of mLNs may predict prognosis more accurately than the current classification system. Our study provides the concept that supports the subdivision of nodal classification in the upcoming revision of the tumor, node, and metastasis staging system.

14.
Lancet Respir Med ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34454653

RESUMO

BACKGROUND: Bevacizumab is a promising candidate for combination treatment with epidermal growth factor receptor tyrosine-kinase inhibitors (eg, erlotinib), which could improve outcomes for patients with metastatic EGFR-mutant non-small-cell lung cancer (NSCLC). We have previously shown in NEJ026, a phase 3 trial, that the combination of bevacizumab plus erlotinib significantly prolonged progression-free survival compared with erlotinib alone in these patients. In further analyses, we aimed to examine the effects of bevacizumab-erlotinib on overall survival, time from enrolment to progressive disease during second-line treatment or death, and quality of life. METHODS: This open-label, randomised, multicentre, phase 3 trial (NEJ026) was done in 69 hospitals and medical, community-based centres across Japan. Eligible patients had stage IIIB, stage IV, or postoperative recurrent, EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg point mutation) NSCLC, had not previously received systemic chemotherapy, and were randomly assigned (1:1) by a computer-generated randomisation sequence and minimisation to receive either 150 mg oral erlotinib once daily plus 15 mg/kg intravenous bevacizumab once every 21 days, or 150 mg oral erlotinib once daily, until disease progression or intolerable toxicity. Randomisation was stratified according to sex, smoking status, EGFR mutation subtype, and clinical disease stage. All participants, investigators, and study personnel (including those assessing outcomes) were unmasked to treatment allocation. We report the secondary outcomes of overall survival and quality of life (the period from enrolment to confirmation of a minimally important difference on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30), and the exploratory outcome of time from enrolment to progressive disease during second-line treatment or death. Overall survival and the exploratory outcome were analysed in the modified intention-to-treat population, which comprised all randomly assigned patients who received at least one dose of the study drug and had response evaluations. Quality of life was analysed in patients in the modified intention-to-treat population who had completed the quality of life questionnaires. The trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, UMIN000017069, and the Japan Registry of Clinical Trials, jRCTs031180056, and is currently closed. FINDINGS: Between June 3, 2015, and Aug 31, 2016, 228 patients were enrolled. 112 patients who received bevacizumab-erlotinib and 112 who received erlotinib only were included in the modified intention-to-treat population. At data cutoff (Nov 30, 2019) and a median follow-up of 39·2 months (IQR 23·9-43·5), the median overall survival was 50·7 months (95% CI 37·3-not estimable [NE]) in the bevacizumab-erlotinib group and 46·2 months (38·2-NE) in the erlotinib-only group (hazard ratio [HR] 1·007, 95% CI 0·681-1·490; p=0·97). In analysis of the exploratory outcome, after a median follow-up of 23·9 months (IQR 14·2-39·1), the median time from enrolment to progressive disease during second-line treatment or death was 28·6 months (95% CI 22·1-35·9) in the bevacizumab-erlotinib group and 24·3 months (20·4-29·1) in the erlotinib-only group (HR 0·773, 95% CI 0·562-1·065). The median time between enrolment and confirmation of a minimally important difference on the EORTC QLQ-C30 was 6·0 months (95% CI 5·2-11·3) in the bevacizumab-erlotinib group and 8·3 months (5·7-13·9) in the erlotinib-only group (p=0·47). INTERPRETATION: The addition of bevacizumab to erlotinib did not prolong survival in patients with metastatic EGFR-mutant NSCLC, but both treatment groups had relatively long survival durations. Why the addition of bevacizumab to erlotinib did not affect overall survival is unclear, but it is possible that the beneficial effects of combination therapy were not seen because overall survival was influenced by treatment regimens used after disease progression. FUNDING: Chugai Pharmaceutical.

15.
Gastroenterology ; 161(6): 1878-1886.e2, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34389340

RESUMO

BACKGROUND & AIMS: Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC. METHODS: Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/m2) on days 1-4 and cisplatin (70 mg/m2) on day 1 every 4 weeks with concurrent radiation (60 Gy). RESULTS: From December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [<1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm. CONCLUSIONS: CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.

16.
Clin Lung Cancer ; 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34321190

RESUMO

BACKGROUND: The aim of this study was to investigate and compare the clinical behaviors of combined and pure high-grade neuroendocrine carcinoma (large-cell neuroendocrine carcinoma [LCNEC] and small-cell lung carcinoma [SCLC]). PATIENTS AND METHODS: Data of 132 patients who underwent complete resection for combined or pure high-grade neuroendocrine carcinoma (combined group, 67; pure group, 65) between January 2001 and December 2015 were retrospectively reviewed. The clinicopathological features were analyzed and compared, and the prognoses were assessed by performing the Kaplan-Meier method and Cox regression analysis. RESULTS: The combined and pure groups had nearly equivalent clinicopathological characteristics, specifically, older males with smoking history, almost the same percentage of pleural/lymphatic/vascular invasion, and nearly the same recurrence rates and relapse patterns. The combined group had prognosis equivalent to that of the pure group (5-year overall survival [OS] rates: 61.8% vs. 52.2%, respectively; P = .82 and 5-year recurrence-free survival [RFS] rates: 42.4% vs. 43.9%, respectively; P = .96), and this trend was identified in sub-analyses only for patients with LCNEC, SCLC, and the same pathological stage. Multivariable Cox regression analysis in patients with high-grade neuroendocrine carcinoma revealed that vascular invasion and pathological stage were independent prognostic factors for OS; more importantly, combined and pure histologies were proven to have nearly equivalent associations with prognosis (hazard ratio, 0.96; 95% confidence interval, 0.22to 1.66; P = .96). RESULTS: Combined high-grade neuroendocrine carcinoma had clinical behavior equivalent to those of pure high-grade neuroendocrine carcinoma, with similar clinicopathological characteristics.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34218331

RESUMO

PURPOSE: Liquid biopsy for early-stage lung cancer diagnosis is challenging, and optimal candidates' clinicopathological features are unknown. We investigated utility and clinicopathological features of optimal candidates in somatic mutation-targeted liquid biopsy using droplet digital polymerase chain reaction (ddPCR) in pN0M0 EGFR mutation-positive lung adenocarcinoma patients. METHODS: We performed EGFR mutation-targeted ddPCR liquid biopsy in 100 patients with resected pN0M0 invasive lung adenocarcinoma, whose tumor diameter in high-resolution computed tomography (HRCT) was ≤ 5 cm. Peripheral blood-derived serum was collected preoperatively. Two representative EGFR somatic variants (exon 19 [E746-A750 del (2235_2249 del)]; exon 21 (L858R)) were utilized as liquid biopsy targets. Clinicopathological features including radiological appearance, subhistology, and invasive status were compared between ddPCR-positive and ddPCR-negative patients. RESULTS: Among the 100 patients, 98 showed part-solid or pure-solid appearance in HRCT and 2 showed non-solid appearance; 98 were pathological stage IA1-IB. Of the 66 patients with EGFR mutation detection in ddPCR, 12 were significantly positive and 10 (83.3%, 10/12) exhibited pure-solid appearance in HRCT. Clinical invasive tumor ratio was significantly higher in ddPCR-positive than in ddPCR-negative patients (median: 100% vs. 85.4%, P = 0.0212), whereas other clinicopathological features were not significantly different. CONCLUSION: Mutation-targeted liquid biopsy using ddPCR detected lung cancer in 12.0% (12/100) of pN0M0 EGFR-mutant lung adenocarcinoma patients. In 83.3% of the ddPCR-positive patients, tumors showed pure-solid appearance in HRCT. The detection ratio increased to 21.3% (10/47) among patients with pure-solid appearance tumors. Tumor appearance might be useful for better selection of liquid biopsy candidates.

18.
Intern Med ; 60(13): 2047-2053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193774

RESUMO

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Piridinas , Sorafenibe/uso terapêutico
20.
Ann Surg Oncol ; 28(13): 8347-8355, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34296359

RESUMO

BACKGROUND: Segmentectomy has been increasingly used for lung cancer treatment, however there are very limited data evaluating the postoperative pulmonary function of patients treated with complex segmentectomy. We evaluated the postoperative pulmonary function of patients who underwent complex segmentectomy compared with simple segmentectomy, wedge resection, and lobectomy. METHODS: We retrospectively analyzed data from 580 patients who underwent surgical resection. The patients were divided into four groups: complex segmentectomy (n = 135), simple segmentectomy (n = 83), wedge resection (n = 89), and lobectomy (n = 273). Functional testing included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and predicted diffusing capacity of the lung for carbon monoxide (%DLCO) measured preoperatively and at 12 months after surgery. RESULTS: During the postoperative course, the complex segmentectomy and simple segmentectomy groups showed a comparable course of pulmonary function. The complex segmentectomy group significantly preserved pulmonary function compared with the lobectomy group (FVC, p = 0.017; FEV1, p = 0.010; %DLCO, p = 0.0043). A similar trend was observed even when restricted to lung diseases in the right upper lobe. On the other hand, when comparing complex segmentectomy with wedge resection, complex segmentectomy showed a trend that was more disadvantageous than wedge resection, but this difference was not significant (FVC, p = 0.19; FEV1, p = 0.40; %DLCO, p = 0.96). CONCLUSIONS: Complex segmentectomy showed comparable postoperative pulmonary functions as simple segmentectomy. Complex segmentectomy could preserve pulmonary function significantly compared with lobectomy and did not result in significant loss compared with wedge resection.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Volume Expiratório Forçado , Humanos , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Estudos Retrospectivos
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