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1.
Jordan A. Torok Lin Gu Daniel J. Tandberg Xiaofei Wang David H. Harpole Chris R. Kelsey Joseph K. Salama 《Clinical lung cancer》2017,18(1):e57-e70
Background
Patients with limited metastases, oligometastases (OMs), might have improved outcomes compared with patients with widespread distant metastases (DMs). The incidence and behavior of OMs from non–small-cell lung cancer (NSCLC) need further characterization.Patients and Methods
The medical records of patients who had undergone surgery for stage I-III NSCLC from 1995 to 2009 were retrospectively reviewed. All information pertaining to development of the first metastatic progression was recorded and analyzed. Patients with DMs were categorized into OMs (1-3 lesions potentially amenable to local therapy) and DM subgroups.Results
Of 1719 patients reviewed, 368 (21%) developed DMs with a median follow-up period of 39 months. A single lesion was diagnosed in 115 patients (31%) and 69 (19%) had 2 to 3 lesions (50% oligometastatic). The median survival from the DM diagnosis for oligometastatic and diffuse DM was 12.4 and 6.1 months, respectively (hazard ratio, 0.54; 95% confidence interval, 0.42-0.68; P < .001). Patients with a single metastasis had the longest median survival at 14.7 months. Younger age, OM, the use of chemotherapy for the primary tumor, and DM detection by surveillance imaging were independently associated with improved survival.Conclusion
DMs and OMs are common in surgically managed NSCLC. Overall survival appears to be prolonged with OM. 相似文献2.
T. Hackert W. Niesen U. Hinz C. Tjaden O. Strobel A. Ulrich C.W. Michalski M.W. Büchler 《European journal of surgical oncology》2017,43(2):358-363
Background
In metastatic disease (M1), chemotherapy (expected survival: 6–10 months) is considered the only treatment option. The aim of this study was to evaluate the outcome of curative M1 PDAC resections.Methods
Prospective data of all patients undergoing primary tumour and metastasis resection for stage IV PDAC during a 12-year period was analysed regarding localisation (liver or distant interaortocaval lymph nodes; ILN), morbidity and survival. Patients were stratified with regard to syn- or metachronous metastases resection.Results
Patients (n = 128) undergoing PDAC and metastases resection (intention-to-treat, oligometastatic stage; liver n = 85; ILN n = 43) were included. Surgical morbidity and 30-day mortality after synchronous resection of M1 tumours were 45% and 2.9%, respectively. Overall median survival after M1 resection was 12.3 months in both groups. Long-term outcome showed a 5-year survival of 8.1% after surgery for both liver metastases and 10.1% following ILN resection.Conclusions
The present collective is the largest series of resected metastatic PDAC and shows that resection of liver or ILN metastases can be done safely and should be considered as it may be superior to palliative treatment, and it is associated with long-term survival of 10% in selected patients. Further studies to stratify patients for these procedures are warranted. 相似文献3.
Mark Zaki Michael Dominello Gregory Dyson Shirish Gadgeel Antoinette Wozniak Steven Miller Peter Paximadis 《Clinical lung cancer》2017,18(1):e21-e26
Background
The objective of this study was to review our institution's experience among patients with locally advanced non–small-cell lung cancer (LA-NSCLC) treated with chemotherapy and radiation and to determine the prognostic significance of age.Patients and Methods
Patients were included if they underwent sequential or concurrent chemoradiotherapy from 2006 to 2014 for LA-NSCLC. Patients were stratified according to age ≤70 and >70 years. Kaplan–Meier and Cox regression methods were performed to evaluate overall survival (OS) and progression-free survival (PFS).Results
One hundred twenty-three patients were identified. Ninety-eight patients were 70 years of age or younger and 25 patients were older than 70 years of age. The median radiotherapy dose was 6660 cGy (range, 3780-7600 cGy). A greater percentage of elderly patients were men, 72% (18 patients) versus 39% (38 patients) (P = .006) and received carboplatin/paclitaxel-based chemotherapy, 60% (15 patients) versus 21% (20 patients) (P < .001). Median follow-up for OS was 25.9 (95% confidence interval [CI], 21.3-33.9) months. There was no difference in the PFS of older patients versus younger patients (hazard ratio [HR], 1.15; P = .64), adjusted for significant covariates. The 1-year PFS rate for patients 70 years of age or younger was 51% (95% CI, 42%-63%) versus 45% (95% CI, 28%-71%) in patients older than 70 years. After adjusting for significant covariates, there was no difference in the OS of older patients compared with younger patients (HR, 1.18; P = .65). The 1-year OS rate for patients 70 years of age or younger was 77% (95% CI, 68%-86%) versus 56% (95% CI, 39%-81%) in patients younger than 70 years.Conclusion
Chemoradiotherapy is an effective treatment in elderly patients with LA-NSCLC, with outcomes similar to that in younger patients. Appropriately selected elderly patients should be considered for chemoradiation. 相似文献4.
Tianhong Li Bilal Piperdi William V. Walsh Mimi Kim Laurel A. Beckett Rasim Gucalp Missak Haigentz Venu G. Bathini Huiyu Wen Kaili Zhou Patricia B. Pasquinelli Srikanth Gajavelli Meera Sreedhara Xianhong Xie Primo N. Lara David R. Gandara Roman Perez-Soler 《Clinical lung cancer》2017,18(1):60-67
Background
Pharmacodynamic separation of pemetrexed and erlotinib avoids negative cellular interactions and results in antitumor synergy in erlotinib-resistant non–small-cell lung cancer (NSCLC) cells, independent of EGFR (epidermal growth factor receptor) genotype.Patients and Methods
Patients with platinum-treated metastatic nonsquamous NSCLC were randomly assigned 1:2 to pemetrexed alone (500 mg/m2 provided intravenously on day 1) or pemetrexed followed by erlotinib (150 mg provided orally once daily on days 2-17) every 21 days. EGFR genotype was centrally confirmed by Sequenom multiplex oncogenotyping assay. The primary end point was progression-free survival (PFS), which would be considered promising for future study if median PFS was ≥ 4.5 months.Results
Of 83 patients enrolled, 79 were randomized to either pemetrexed alone (n = 27) or in combination (n = 52). Fifty-nine (79%) of 75 eligible patients had tumors with confirmed EGFR genotype: 7 with activating mutations and 52 wild type. Median PFS was 4.7 and 2.9 months in the combination and pemetrexed-alone groups, respectively. In patients with EGFR wild-type tumors, median PFS was 5.3 and 3.5 months in the combination and pemetrexed-alone groups, respectively. Objective response rate (29% vs. 10%, P = .17), 6-month PFS (45% vs. 29%, P = .26), and 12-month PFS (23% vs. 10%, P = .28) were all higher in the combination arm. Rash (67% vs. 26%, P = .0007) and diarrhea (44% vs. 11%, P = .003) were significantly more common in the combination arm.Conclusion
In patients with unselected or EGFR wild-type advanced nonsquamous NSCLC, pharmacodynamic separation of pemetrexed and intercalated erlotinib had promising antitumor activity without new safety concerns. The combination merits further evaluation as maintenance or second-line therapy against new standards in patients with EGFR wild-type advanced NSCLC. 相似文献5.
Tao Jiang Meng Qiao Fei Zhou Shengxiang Ren Chunxia Su Caicun Zhou 《Clinical lung cancer》2017,18(4):421-431.e3
Background
To investigate the effect of combined epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway inhibitors on progression-free survival (PFS) and overall survival (OS) in patients with non–small-cell lung cancer (NSCLC).Materials and Methods
We included 15 randomized clinical trials that had compared the combination of EGFR tyrosine kinase inhibitors and anti-VEGF/VEGFR therapy with different control groups. Pooled estimates of treatment efficacy were calculated, and subgroup analyses were conducted according to treatment line and EGFR status.Results
Ten of 15 trials involving 3317 NSCLC patients were included. For all settings, the combined regimen demonstrated no PFS (hazard ratio [HR], 0.82; P = .10) or OS (HR, 0.97; P = .54) benefit compared with the control groups. In the first-line setting, combined therapy showed similar PFS (HR, 1.01; P = .99) but poor OS (HR, 1.36; P = .03) compared with the control groups. In the second-line or subsequent settings, combined therapy resulted in significantly longer PFS (HR, 0.75; P < .01) but similar OS (HR, 0.93; P = .16) compared with the control groups. A subgroup analysis stratified by EGFR status suggested that combined treatment substantially improved PFS (HR, 0.57; P = .04) and OS (HR, 0.45; P < .01) in patients with EGFR mutations rather than EGFR wild type.Conclusion
EGFR-tyrosine kinase inhibitors plus anti-VEGF/VEGFR therapy significantly prolonged PFS in the second-line treatment of NSCLC patients. An EGFR mutation is a promising indication for this combination treatment. More data are required to confirm this strategy in first-line therapy. 相似文献6.
Oliver Gautschi Sacha I. Rothschild Qiyu Li Klazien Matter-Walstra Alfred Zippelius Daniel C. Betticher Martin Früh Rolf A. Stahel Richard Cathomas Daniel Rauch Miklos Pless Solange Peters Patrizia Froesch Thilo Zander Martina Schneider Christine Biaggi Nicolas Mach Adrian F. Ochsenbein 《Clinical lung cancer》2017,18(3):303-309
Background
Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non–small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone.Patients and Methods
We conducted a nonrandomized phase II trial with 2 sequential cohorts. In the first cohort, 77 patients were treated with 4 cycles of cisplatin, bevacizumab, and pemetrexed every 3 weeks, followed by bevacizumab plus pemetrexed maintenance until progression. In the second cohort, we treated 52 patients without bevacizumab, using maintenance with pemetrexed alone. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), adverse events, and the treatment costs of the 2 cohorts were compared.Results
The median PFS from the time of registration was 6.9 months in cohort 1 and 5.6 months in cohort 2. The ORR was 62.3% in cohort 1% and 44.2% in cohort 2. The PFS (hazard ratio, 0.7; 95% confidence interval [CI], 0.5-1.0; P = .041) and ORR (odds ratio, 2.1; 95% CI, 1.0-4.3; P = .049) were better in cohort 1 than in cohort 2. No OS difference was found (hazard ratio, 1.0; 95% CI, 0.7-1.6; P = .890) after a median follow-up period of 47 months for cohort 1 and 27 months for cohort 2. The rate of grade ≥ 3 adverse events was greater in cohort 1. The treatment costs per patient were on average 1.4 times greater for cohort 1.Conclusion
The addition of bevacizumab increased the ORR and PFS, but not OS, in our nonrandomized trial. Furthermore, the addition of bevacizumab was associated with greater toxicity and higher costs. 相似文献7.
Introduction
We examined the value of tumor location in predicting the clinicopathologic features, survival, and metastases of pulmonary adenocarcinoma.Patients and Methods
A total of 417 cases of pulmonary adenocarcinoma were included in the present study. The tumors with invasion of the segmental and/or lobar bronchus were classified as central adenocarcinoma and those without as peripheral adenocarcinoma. Histologic grade, cytologic features, and adenocarcinoma type (terminal respiratory unit [TRU] type vs. non-TRU type) were compared between the 2 groups. The prognostic factors for disease-free survival (DFS) were analyzed using univariate and multivariate analyses.Results
Central adenocarcinoma was associated with lymphatic and/or vascular invasion (P = .011), necrosis (P < .001), high histologic grade (P = .004), and advanced stage (P < .001). For lung adenocarcinoma 1 to 4 cm in size, central adenocarcinoma was linked to a greater rate of nodal metastasis than peripheral adenocarcinoma. However, for lung adenocarcinoma of other sizes, central and peripheral adenocarcinoma had no differences in the rates of nodal metastasis. For nuclear features, central adenocarcinoma showed high mitotic counts, advanced nuclear atypia, and larger nuclei (P < .001, P < .001, P < .001, respectively). More peripheral adenocarcinomas than central adenocarcinomas were TRU type (229 of 281 [81.5%] vs. 58 of 136 [42.6%]; P < .001). Multivariate survival analyses of DFS showed that tumor location (central vs. peripheral, hazard ratio, 1.744; P < .001) was a stage-independent prognostic factor.Conclusion
Central adenocarcinoma is associated with a high potential for regional lymph node metastases, even at a small size. The results of our study showed that tumor location is an important factor for choosing treatment strategies and predicting DFS. 相似文献8.
Tao Jiang Ruirui Cheng Guowei Zhang Chunxia Su Chao Zhao Xuefei Li Jie Zhang Fegnying Wu Xiaoxia Chen Guanghui Gao Wei Li Weijing Cai Fei Zhou Jing Zhao Anwen Xiong Shengxiang Ren Guojun Zhang Caicun Zhou Jun Zhang 《Clinical lung cancer》2017,18(6):631-639.e2
Background
The risk factors for liver metastasis (LM) in patients with non–small-cell lung cancer (NSCLC) remain unknown. Whether LM predicts for the effect of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant NSCLC needs to be explored.Patients and Methods
A total of 598 NSCLC patients from 3 centers underwent EGFR testing, and 293 had EGFR-mutant NSCLC. Of the 598 NSCLC patients, 99 had LM; 56 patients with EGFR-mutant NSCLC received EGFR-TKIs as first-line therapy.Results
EGFR mutation was not associated with LM in NSCLC patients (relative ratio, 1.305, P = .261). In the EGFR-mutant group that received first-line EGFR-TKIs, patients with LM had shorter progression-free survival (PFS; 7.5 vs. 11.8 months; P = .0003) and overall survival (OS; 20.8 vs. 30.6 months; P = .0190) than patients without LM. The significant difference in PFS was observed in both patients with EGFR exon 19 deletion (19del) and Leu858Arg mutation (L858R). However, patients with EGFR 19del and LM showed marginally significantly shorter OS (P = .0531) and patients with EGFR L858R and LM had OS similar to that of patients without LM (P = .1883). Regardless of EGFR status, patients with LM who received first-line chemotherapy had PFS and OS similar to those of patients without LM. Univariate analyses identified only never smoking (hazard ratio, 0.536; P = .012) was significantly associated with better OS for patients with NSCLC and LM.Conclusion
EGFR mutation is not an independent risk factor for LM in NSCLC patients. However, the presence of LM is a negative predictive factor for first-line EGFR-TKI therapy for patients with EGFR-mutant NSCLC. 相似文献9.
Matthew D. Johnson Karna Sura Victor S. Mangona Alexander Glick Michelle Wallace Hong Ye Inga S. Grills 《Clinical lung cancer》2017,18(2):149-155
Background
Recent data have called into question the use of dose-escalated radiotherapy for locally advanced non–small-cell lung cancer and the effect of cardiac radiotherapy doses. We compared the outcomes after chemoradiation using standard-dose (SD; ≤ 64 Gy) or high-dose (HD; > 64 Gy) radiotherapy.Patients and Methods
A matched-pair analysis was performed of 178 patients with stage IIB-IIIB non–small-cell lung cancer for SD versus HD groups using age ± 5 years, gender, stage, tumor size ± 2 cm, yielding 86 patients. The clinical endpoints were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox regression method.Results
The median follow-up was 16.8 months for the entire cohort (HD, 21.6 months; SD, 12.1 months; P = .06). No significant differences were found in disease stage, histologic type, age, performance status, gender, or tumor size between the 2 groups. The median overall survival was 23.1 months for the HD group (95% confidence interval, 20.6-25.5) versus 13.6 months for the SD group (95% confidence interval, 9.6-17.5; P = .03). The 2-year freedom from locoregional recurrence was 48.7% for the SD and 65.3% for the HD groups (P = .07). The 2-year freedom from distant metastasis was 46.7% for the SD and 70.3% for the HD groups (P = .05). A higher cardiac V30 dose (P = .03) was the strongest predictor of survival besides clinical stage (P = .02).Conclusion
Dose-escalated radiotherapy resulted in improved survival and recurrence rates. A higher cardiac dose was a significant predictor of decreased survival. 相似文献10.
Y.-W. Hong I.-M. Kuo Y.-Y. Liu T.-S. Yeh 《European journal of surgical oncology》2017,43(10):1886-1893
Introduction
Information on primary small intestinal lymphoma is more limited than for gastric lymphoma because most of the previous studies did not focus on the former. Few prognostic indicators in primary intestinal lymphoma have been reliably established because of limited patient numbers and variations in criteria for patient selection. In this study, we retrospectively reviewed the clinical and pathological characteristics of small intestinal lymphoma cases from our hospital, to determine prognostic factors and to clarify the effect of surgical resection on prognosis.Methods
Eighty-two patients were enrolled in this retrospective study between January 1997 and December 2012. Patients were divided into two groups based on whether or not they underwent surgical management. Gross resection was defined as complete removal of the primary lesion(s), as confirmed by the naked eye. Combined therapy refers to concurrent surgery and chemotherapy. The clinicopathological characteristics and long-term outcomes of patients were analyzed and compared between the two groups.Results
Most of the patients had abdominal pain (75.6%), and some had loss of body weight (29.3%) and bowel perforation (22.0%). Sixty-two patients (75.6%) underwent surgical management. Patients in the surgery group presented with fewer B symptoms (fever, night sweats, and weight loss; P = 0.035) but more bulky disease (P = 0.009). The ileocecal region was the most common site of solitary involvement (34.1%). The most common reason for surgery was for tumor-related complications (61.3%). Seven patients (11.3%) developed major complications of surgery, but these were not related to the indication, timing, or type of surgery. Only major surgical complications were statistically significant in relation to early mortality (P = 0.004). The estimated 5-year progression-free survival (PFS) was 35.1% and 5-year overall survival (OS) was 43.2%. Univariate analysis revealed that patients in the surgery group had improved 5-year PFS (P = 0.028). T-cell lymphoma, involvement of multiple gastrointestinal regions and extranodal involvement, higher scores for International Prognostic Index (IPI), more advanced Ann Arbor stage, lactate dehydrogenase (LDH) levels above 215 U/L, and management without combined therapy were prognostic for shorter PFS and OS in univariate analyses. Individuals who received R0 resection or gross resection had improved 5-year PFS and OS. Cox regression analysis demonstrated that primary T-cell lymphoma was an independent negative prognostic factor for both OS and PFS.Conclusion
Combined therapy is an independent prognostic factor for long-term survival in small intestinal lymphoma. Gross resection is recommended in patients with small intestinal lymphoma and leads to improved PFS without significantly increasing the risk of complications. Emergency surgery does not lead to poor prognosis. However, caution is warranted in the management of all patients, because of the high risk of post-operative complications and potential for early mortality. 相似文献11.
Mihong Choi Youngjoo Lee Sung Ho Moon Ji-Youn Han Heung Tae Kim Jin Soo Lee 《Clinical lung cancer》2017,18(1):77-84
Background
Prophylactic cranial irradiation (PCI) was reported to offer survival benefits in patients with limited stage small-cell lung cancer (LS-SCLC). However, earlier studies did not routinely use positron emission tomography (PET) as part of the initial evaluation, thereby reducing the accuracy of tumor staging. We examined the effect of more accurate staging with PET on the role of PCI in patients with LS-SCLC.Patients and Methods
We retrospectively collected data from 280 patients with LS-SCLC who had objective responses after combined chemoradiotherapy between 2001 and 2013. The outcomes of PCI were analyzed after stratifying the patients according to whether or not the initial staging included PET imaging.Results
The risk of brain metastasis as the first site of relapse was lower in patients who received PCI than in those who did not, only in patients without initial PET imaging (13.3% vs. 37.0%; P = .020), but not in patients with initial PET imaging (34.3% vs. 41.1%; P = .243). There was no survival difference between subgroups who received PCI or not (5-year survival rates, 34.8% vs. 34.1%; P = .938). Patients who had initial staging evaluation with PET achieved long-term survival even without PCI (5-year survival rates, 38.3% with PCI, 38.6% without PCI).Conclusion
The role of PCI needs to be critically reassessed in LS-SCLC patients whose initial staging evaluation included PET because the benefit of PCI was not apparent for them. 相似文献12.
K. Lehmann D. Eshmuminov P. Bauerfeind C. Gubler P. Veit-Haibach A. Weber H. Abdul-Rahman M. Fischer C. Reiner P.M. Schneider 《European journal of surgical oncology》2017,43(1):196-202
Introduction
The accuracy of preoperative lymph-node staging in patients with adenocarcinoma of the esophagogastric junction (AEG) or gastric cancer (GC) is low. The aim of this study was to assess the accuracy of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) for lymph-node staging in patients with AEG or GC, with or without neoadjuvant treatment.Patients and methods
221 consecutive patients with GC (n = 88) or AEG (n = 133) were evaluated. Initial staging included endoscopic ultrasound (EUS), multidetector spiral CT (MDCT) and PET-CT. PET-CT was performed for restaging in patients after neoadjuvant treatment (n = 94). Systematic lymphadenectomy was routinely performed with histopathological assessment of individual mediastinal and abdominal lymph-node stations. Preoperative staging from EUS, MDCT, and PET-CT was correlated with histopathological results.Results
PET-CT showed a high specificity (91%) and positive predictive value (89%) for the preoperative detection of lymph-node metastases. In comparison, EUS was more sensitive (73% versus 50%, P < 0.01) but less specific (60%, P < 0.01). In patients with intestinal/mixed-type tumors, PET-CT improved the detection of extra-regional lymph-node metastases (P = 0.01) and distant metastases (P = 0.01) compared to CT alone. In contrast, lymph-node assessment by PET/CT after neoadjuvant treatment (32%, P < 0.01) and in diffuse-type cancers (24%, P < 0.01) is futile because of low sensitivities.Conclusion
PET-CT does not improve the overall accuracy of N staging, but does improve specificity compared to EUS and MDCT in AEG and GC. We do not recommend routine PET-CT for the initial staging in patients with diffuse-type cancer or for restaging of lymph nodes after neoadjuvant treatment. 相似文献13.
Bo Qiu Ying Liang QiWen Li GuiHong Liu Fang Wang ZhaoLin Chen MengZhong Liu Ming Zhao Hui Liu 《Clinical lung cancer》2017,18(6):e369-e373
Introduction
The effect of local therapy (LT) for oligoprogressive epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) has not been well established. Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC were treated by LT and continuing tyrosine kinase inhibitors (TKIs) for oligoprogression. The median overall survival (OS) and progression-free survival (PFS) after LT were 13.0 and 7.0 months, respectively. EGFR mutation type, sites of LT, and time from first progressive disease (PD) to LT were prognostic of OS after LT.Purpose
Patients with advanced stage EGFR-mutated NSCLC treated with EGFR TKIs could experience oligoprogression. This study investigated the benefits of LT and continuation of TKIs for oligoprogression retrospectively.Materials and Methods
Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC on TKIs were treated by LT and continuation of TKIs for oligoprogressive disease. The impact of clinicopathologic variables on survival was explored using Cox regression.Results
With a median follow-up of 32 months, the 2-year OS was 65.2%, and the estimated OS was 35.0 months. The median OS after LT (LT-OS) was 13.0 months. The median PFS after LT (LT-PFS) was 7.0 months. Univariate analysis showed that stage at initial diagnosis, EGFR mutation type, site of LT, metastatic status at initial TKIs, and time from first PD to LT correlated with LT-OS significantly. Multivariate analysis suggested that EGFR mutation type (P = .001), sites of LT (P = .000), and time from first PD to LT (P = .034) were prognostic of LT-OS. Univariate analysis showed that metastatic status at initial TKIs and time from first PD to LT correlated with LT-PFS significantly. Multivariate analysis suggested that only time from first PD to LT (P = .000) was prognostic of LT-PFS.Conclusion
This study revealed that LTs are feasible and effective for EGFR-mutated NSCLC with oligoprogression. EGFR mutation type, sites of LT, and time from first PD to LT were prognostic factors for LT-OS. Time from first PD to LT was a prognostic factor for LT-PFS. 相似文献14.
Bonnie Glisson Benjamin Besse Manuel Cobo Dols Sarita Dubey Marco Schupp Rajul Jain Yizhou Jiang Hari Menon Kristiaan Nackaerts Sergey Orlov Luis Paz-Ares Rodryg Ramlau Rui Tang Yilong Zhang Min Zhu 《Clinical lung cancer》2017,18(6):615-625.e8
Introduction/Background
In this randomized, double-blind, placebo-controlled phase 1b/2 study we assessed the efficacy/safety of rilotumumab or ganitumab combined with etoposide and carboplatin or cisplatin as first-line treatment in patients with extensive stage small-cell lung cancer (ES-SCLC).Patients and Methods
In the phase 1b study, patients received rilotumumab 15 mg/kg or ganitumab 18 mg/kg with etoposide and carboplatin or cisplatin. In the phase 2 study, patients were randomly assigned 1:1:1 to receive placebo, rilotumumab, or ganitumab with etoposide and carboplatin or cisplatin. Chemotherapy was administered for ≤ 6 cycles; rilotumumab, ganitumab, or placebo was then continued as maintenance therapy. The primary end points were incidence of dose-limiting toxicities (DLTs; phase 1b) and overall survival (OS; phase 2). Secondary end points included progression-free survival (PFS) and safety.Results
In the phase 1b study (n = 28), 1 patient treated with ganitumab experienced a DLT (Grade 4 neutropenia/thrombocytopenia lasting ≥ 7 days). In the phase 2 study, 185 patients were enrolled (placebo, n = 61; rilotumumab, n = 62; ganitumab, n = 62). Median OS was 10.8, 12.2 (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.56-1.25; P = .384), and 10.7 (HR, 0.95; 95% CI, 0.63-1.41; P = .787) months, in placebo, rilotumumab, or ganitumumab arms, respectively. Median PFS was 5.4, 5.4 (HR, 1.05; 95% CI, 0.71-1.54; P = .797), and 5.5 (HR, 1.05; 95% CI, 0.72-1.55; P = .780) months, respectively. Adverse events resulting in treatment discontinuation occurred in 11 (19%), 10 (16%), and 7 (12%) patients, respectively. Serum biomarker analysis showed improved survival for patients with baseline hepatocyte growth factor levels below the median in the rilotumumab arm.Conclusion
Although the combination of rilotumumab or ganitumab with chemotherapy was tolerable, overall outcomes were not improved in patients with ES-SCLC. 相似文献15.
Yu Jin Lim Ji Hyun Chang Hak-Jae Kim Bhumsuk Keam Tae Min Kim Dong-Wan Kim Jin Chul Paeng Keon Wook Kang June-Key Chung Yoon Kyung Jeon Doo Hyun Chung Hong-Gyun Wu 《Clinical lung cancer》2017,18(3):e169-e178
Background
Although previous in vitro data have suggested a more radio-sensitive nature of epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC) cell lines, the clinical behavior according to the EGFR mutational status has not been well-established. In this study, we performed a comparative outcome analysis of EGFR-mutant and wild-type locally advanced NSCLC with chemoradiotherapy (CRT).Patients and Methods
A total of 102 patients with stage III nonsquamous NSCLC undergoing primary CRT were identified. Clinicopathologic characteristics, including the degree of glucose uptake, were evaluated. Failure patterns considering the radiation field and survival outcomes were compared according to the EGFR mutational status.Results
Pre- and post-CRT maximum standardized uptake values were significantly lower in EGFR-mutant tumors (P = .010 and .018, respectively). The overall response rate was higher in the EGFR-mutant group compared with the wild-type (89% vs. 64%, respectively; P = .023). The 3-year overall survival rate was better with the genetic alteration (68.0% vs. 47.4%, P = .046), but the statistical significance did not remain in multivariate analysis (hazard ratio, 0.68; 95% confidence interval, 0.30-1.55). Considering the tumor progression inside or outside the radiation field, the EGFR-mutant group showed longer in-field time to progression (P = .002), even after adjusting for other related baseline variables (hazard ratio, 0.27; 95% confidence interval, 0.11-0.71).Conclusion
The differential metabolic activity, failure patterns, and prognosis suggest the distinct nature of the EGFR-mutant tumors. EGFR mutational status needs to be considered for more precise curative-intent treatment strategies of locally advanced nonsquamous NSCLC. 相似文献16.
In Seob Lee Sol Lee Young Soo Park Chung Sik Gong Jeong Hwan Yook Byung Sik Kim 《Surgical oncology》2017,26(1):8-12
Background
Endoscopic submucosal dissection (ESD) is not considered an appropriate treatment for undifferentiated early gastric cancer (UEGC) due to the higher risk of nodal metastases. We aimed to investigate predictive factors for nodal metastases in UEGCs, determine whether the tumor histology is an independent factor for it, and explore whether ESD is applicable for UEGC.Methods
We reviewed the medical records of 1837 patients who underwent curative gastrectomy for poorly differentiated adenocarcinoma, signet ring cell carcinoma, and a mixed type of both tumors between 2008 and 2012.Results
Nodal metastases were found in 208 (11.3%) patients. Multivariate analysis revealed that lymphovascular invasion and tumor histology were significantly associated with nodal metastases in mucosal cancers, the rates of which were higher in mixed type tumors (6.3%) than in the other two types (2.0–2.5%; p = 0.005). No nodal metastases were observed in poorly differentiated adenocarcinomas <2 cm and signet ring cell carcinomas <1 cm without lymphovascular invasion and confined to the mucosa.Conclusion
Mixed type tumors should not be considered for endoscopic resection. ESD might be applicable for mucosal tumors with poorly differentiated adenocarcinoma <2 cm and signet ring cell carcinoma <1 cm without lymphovascular invasion. 相似文献17.
C.-Y. Tsai C.-J. Yeh Y.-K. Chao H.-K. Chang C.-K. Tseng Y.-H. Liu 《European journal of surgical oncology》2017,43(10):1970-1976
Background
The prognostic impact of perineural invasion (PNI) in patients with esophageal cancer who receive neoadjuvant chemoradiotherapy (nCRT) remains unclear.Methods
A thorough pathological review of PNI was performed on post-nCRT esophagectomy specimens obtained from non-ypT0 patients with esophageal squamous cell carcinoma (ESCC). When PNI was identified, it was classified according to the presence or absence of penetration through the nerve sheath (i.e., PNI surrounding the nerve sheath [PNI-SS] versus PNI penetrating through the nerve sheath [PNI-TS]). The impact of PNI on overall survival (OS) was assessed in combination with clinical and pathological risk factors.Results
A total of 177 eligible patients were identified between 1998 and 2008. PNI was identified in 43.5% (77/177) of participants. Of them, 33 and 44 had PNI-SS and PNI-TS, respectively. The 5-year OS rate of patients with PNI-TS was significantly lower (6.7%) than that observed in those without PNI (30.6%, P < 0.001). However, the 5-year OS observed in the latter group did not differ significantly from that of patients with PNI-SS (26%, P = 0.68). Multivariate analysis identified PNI-TS (hazard ratio [HR] = 1.965, P = 0.02), LVI (HR = 1.514, P = 0.048), and ypN2 stage (HR = 2.39, P = 0.007) as independent adverse prognostic factors for OS.Conclusions
The presence of PNI-TS after nCRT is associated with poor survival. A thorough assessment of distinct PNI patterns (i.e., PNI-TS versus PNI-SS) should be part of the routine post-nCRT histopathological work-up of ESCC patients. 相似文献18.
J.H. Jeon J.M. Lee D.H. Moon H.C. Yang M.S. Kim G.-K. Lee J.I. Zo 《European journal of surgical oncology》2017,43(2):471-477
Background
The purpose of this study was to analyze the risk factors of recurrence in patients with early stage esophageal squamous cell carcinoma (ESCC).Methods
We retrospectively analyzed the medical records of 190 patients with confirmed T1N0M0 ESCC after curative esophagectomy. The following potential prognostic factors for recurrence were investigated: age, sex, pathologic T category, tumor location, differentiation grade, tumor size, venous invasion, angiolymphatic invasion, perineural invasion and the maximum standardized uptake value (SUVmax) of the primary tumor.Results
There were 174 male and 16 female patients with a median age of 66.0 years (range, 42.0–79.0 years). The pathologic status of the surgically resected ESCCs was T1a in 93 patients (48.9%) and T1b in 97 patients (51.1%). The median number of dissected lymph nodes was 35 (range, 10 to 86), and all lymph nodes were negative for tumors. The multivariate analysis showed presence of venous invasion [HR (hazard ratio), 11.433; P < 0.001) and SUVmax ≥ 3.2 (HR, 2.830; P = 0.011) as independent risk factors for recurrence. The 5-year recurrence-free survival (RFS) was 25.0% for patients with venous invasion and 78.9% for those without (P < 0.001). The 5-year RFS was 67.1% for patients with an SUVmax ≥3.2 and 81.5% for those with an SUVmax <3.2 (P = 0.003).Conclusions
Venous invasion and high SUVmax could be important prognostic factors coupled with the TNM staging system, in patients with early stage ESCC. 相似文献19.
Y.-K. Chao W.-Y. Chuang H.-K. Chang C.-K. Tseng C.-J. Yeh Y.-H. Liu 《European journal of surgical oncology》2017,43(1):234-239
Background
The purpose of this study was to investigate the prognosis and its predictors in patients with esophageal squamous cell carcinoma (ESCC) who achieve major histopathological response (MaHR) after neoadjuvant chemoradiotherapy (nCRT).Methods
We examined a total of 187 ESCC patients who achieved MaHR following nCRT and survived the perioperative period. MaHR was defined as either absence or <10% vital residual tumor cells (VRTC) in the resected esophagus without nodal involvement. Univariate and multivariate analyses were used to identify factors significantly associated with overall survival (OS).Results
At the time of analysis, 113 patients (60.4%) were dead (5-year OS = 48%; median survival time = 54.8 months). The amount of VRTC (1–10% versus 0% VRTC; hazard ratio [HR] = 1.9, P < 0.001) and the thoroughness of histopathological examination (standard [≤ 4 tumor blocks] versus thorough [> 4 tumor blocks], HR = 1.57; P = 0.013) were independent predictors of OS in multivariate analysis. A stepwise increase in OS was observed in the following groups: patients with 1–10% VRTC identified by the standard protocol, patients with 1–10% VRTC identified by the thorough protocol, patients with 0% VRTC identified by the standard protocol, and patients with 0% VRTC identified by the thorough protocol (5-year OS rates = 20%, 40%, 50%, and 62%, respectively, P < 0.001).Conclusions
In ESCC patients who achieve MaHR after nCRT, the presence of microscopical residual disease and the thoroughness of histopathological examination are associated with survival. 相似文献20.
Stephan Schorn Ihsan Ekin Demir Bernhard Haller Florian Scheufele Carmen Mota Reyes Elke Tieftrunk Mine Sargut Ruediger Goess Helmut Friess Güralp Onur Ceyhan 《Surgical oncology》2017,26(1):105-115
