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1.
Tetsuhiko Asao Yutaka Fujiwara Kota Itahashi Shinsuke Kitahara Yasushi Goto Hidehito Horinouchi Shintaro Kanda Hiroshi Nokihara Noboru Yamamoto Kazuhisa Takahashi Yuichiro Ohe 《Clinical lung cancer》2017,18(4):e251-e258
Background
Second-generation anaplastic lymphoma kinase (ALK) inhibitors, such as alectinib and ceritinib, have recently been approved for treatment of ALK-rearranged non–small-cell lung cancer (NSCLC). An optimal strategy for using 2 or more ALK inhibitors has not been established. We sought to investigate the clinical impact of sequential use of ALK inhibitors on these tumors in clinical practice.Patients and Methods
Patients with ALK-rearranged NSCLC treated from May 2010 to January 2016 at the National Cancer Center Hospital were identified, and their outcomes were evaluated retrospectively.Results
Fifty-nine patients with ALK-rearranged NSCLC had been treated and 37 cases were assessable. Twenty-six received crizotinib, 21 received alectinib, and 13 (35.1%) received crizotinib followed by alectinib. Response rates and median progression-free survival (PFS) on crizotinib and alectinib (after crizotinib failure) were 53.8% (95% confidence interval [CI], 26.7%-80.9%) and 38.4% (95% CI, 12.0%-64.9%), and 10.7 (95% CI, 5.3-14.7) months and 16.6 (95% CI, 2.9-not calculable), respectively. The median PFS of patients on sequential therapy was 35.2 months (95% CI, 12.7 months-not calculable). The 5-year survival rate of ALK-rearranged patients who received 2 sequential ALK inhibitors from diagnosis was 77.8% (95% CI, 36.5%-94.0%).Conclusion
The combined PFS and 5-year survival rates in patients who received sequential ALK inhibitors were encouraging. Making full use of multiple ALK inhibitors might be important to prolonging survival in patients with ALK-rearranged NSCLC. 相似文献2.
Jose M. Pacheco Dexiang Gao Derek Smith Thomas Purcell Mark Hancock Paul Bunn Tyler Robin Arthur Liu Sana Karam Laurie Gaspar Brian Kavanagh Chad Rusthoven Dara Aisner Robert Doebele D. Ross Camidge 《Journal of thoracic oncology》2019,14(4):691-700
Introduction
Clinical variables describing the natural history and longitudinal therapy outcomes of stage IV anaplastic lymphoma kinase gene rearrangement positive (ALK-positive) NSCLC and their relationship with long-term overall survival (OS) have not previously been described in detail.Methods
Patients with stage IV NSCLC treated with an ALK inhibitor at the University of Colorado Cancer Center from 2009 through November 2017 were identified retrospectively. OS curves were constructed by using Kaplan-Meier methods. Multivariate Cox proportional hazard analysis was used to determine the relationship of variables with OS.Results
Of the 110 patients with ALK-positive NSCLC who were identified, 105 received crizotinib as their initial ALK inhibitor. With a median follow-up time of 47 months, the median OS time from diagnosis of stage IV disease was 81 months (6.8 years). Brain metastases at diagnosis of stage IV disease (hazard ratio = 1.01, p = 0.971) and year of stage IV presentation (p = 0.887) did not influence OS. More organs with tumor at diagnosis of stage IV disease was associated with worse OS (HR = 1.49 for each additional organ with disease, including the CNS [p = 0.002]). Each additional month of pemetrexed-based therapy was associated with a 7% relative decrease in risk of death.Conclusion
Patients with stage IV ALK-positive NSCLC can have prolonged OS. Brain metastases at diagnosis of stage IV disease does not influence OS. Having more organs involved with tumor at stage IV presentation is associated with worse outcomes. Prolonged benefit from pemetrexed is associated with better outcomes. 相似文献3.
Mei-Mei Zheng Yang-Si Li Ben-Yuan Jiang Hai-Yan Tu Wen-Fang Tang Jin-Ji Yang Xu-Chao Zhang Jun-Yi Ye Hong-Hong Yan Jian Su Qing Zhou Wen-Zhao Zhong Xue-Ning Yang Wei-Bang Guo Shannon Chuai Zhou Zhang Hua-Jun Chen Zhen Wang Yi-Long Wu 《Journal of thoracic oncology》2019,14(5):924-932
Introduction
Leptomeningeal metastases (LMs) indicated a poor prognosis in NSCLC. LMs were more frequent in driver gene–mutated patients, and cerebrospinal fluid (CSF) cell-free DNA has shown unique genetic profiles of LM in EGFR-mutated LM. However, studies in patients with ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC with LMs are scarce.Methods
Patients with lung cancer with ALK rearrangement were screened from September 2011 to February 2018 at our institute. CSF and paired plasma were tested by next-generation sequencing.Results
LMs were diagnosed in 30 (10.3%) of 291 patients with ALK-rearranged lung cancer. A total of 11 paired CSF and plasma samples tested by next-generation sequencing were analyzed. Driver genes were detected in 81.8% of the CSF samples (9 of 11) and 45.5% of the plasma samples (5 of 11) (p = 0.183). The maximum allelic fractions were all higher in CSF than in plasma (p = 0.009). ALK and tumor protein p53 gene (TP53) were the two most frequently mutated genes in CSF. Gatekeeper gene ALK G1202R and C1156F mutations were identified in CSF after resistance to alectinib. Multiple copy number variants were mainly found in CSF, including in EGFR, cyclin D1 gene (CCND1), fibroblast growth factor 3 gene (FGF3), and fibroblast growth factor 4 gene (FGF4). Also found were v-myc avian myelocytomatosis viral oncogene homolog gene (MYC) copy number gains and TP53 and cyclin dependent kinase inhibitor 2A gene (CDKN2A) copy number deletions. Brigatinib seemed to be effective in controlling LM. One case showed that CSF could be used to monitor disease development of LM and longitudinally monitor tumor response.Conclusion
Liquid biopsy of CSF is more sensitive than liquid biopsy of plasma to detect targetable alterations, characterizing resistance mechanisms on progression and monitoring tumor response in patients with ALK-rearranged NSCLC with LM. Thus, CSF might be promising as a medium of liquid biopsy in LM. 相似文献4.
Jean-Louis Pujol Laurent Greillier Clarisse Audigier-Valette Denis Moro-Sibilot Lionel Uwer José Hureaux Florian Guisier Delphine Carmier Jeannick Madelaine Josiane Otto Valérie Gounant Patrick Merle Pierre Mourlanette Olivier Molinier Aldo Renault Audrey Rabeau Martine Antoine Marc G. Denis Pierre-Jean Souquet 《Journal of thoracic oncology》2019,14(5):903-913
Introduction
This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum–etoposide chemotherapy.Methods
Patients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O’Brien-Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders.Results
Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval [CI]: 0.0–6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8–33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression-free survival was 1.4 months (95% CI: 1.2–1.5) with atezolizumab and 4.3 months (95% CI: 1.5–5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratioatezolizumab : 0.84, 95% CI: 0.45–1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone).Conclusions
Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed. 相似文献5.
Martin Reck Leora Horn Silvia Novello Fabrice Barlesi István Albert Erzsébet Juhász Dariusz Kowalski Gilles Robinet Jacques Cadranel Paolo Bidoli John Chung Arno Fritsch Uta Drews Andrea Wagner Ramaswamy Govindan 《Journal of thoracic oncology》2019,14(4):701-711
Introduction
This phase II study evaluated the efficacy and safety of the pan-cyclin–dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.Methods
In this randomized, double-blind study, unselected patients with previously untreated extensive-disease SCLC received roniciclib, 5 mg, or placebo twice daily according to a 3 days–on, 4 days–off schedule in 21-day cycles, with concomitant cisplatin or carboplatin on day 1 and etoposide on days 1 to 3. The primary end point was progression-free survival. Other end points included overall survival, objective response rate, and safety.Results
A total of 140 patients received treatment: 70 with roniciclib plus chemotherapy and 70 with placebo plus chemotherapy. Median progression-free survival times was 4.9 months (95% confidence interval [CI]: 4.2–5.5) with roniciclib plus chemotherapy and 5.5 months (95% CI: 4.6–5.6) with placebo plus chemotherapy (hazard ratio [HR] = 1.242, 95% CI: 0.820–1.881, p = 0.8653). Median overall survival times was 9.7 months (95% CI: 7.9–11.1) with roniciclib plus chemotherapy and 10.3 months (95% CI: 8.7–11.9) with placebo plus chemotherapy (HR = 1.281, 95% CI: 0.776–1.912, p = 0.7858). The objective response rates were 60.6% with roniciclib plus chemotherapy and 74.6% with placebo plus chemotherapy. Common treatment-emergent adverse events in both groups included nausea, vomiting, and fatigue. Serious treatment-emergent adverse events were more common with roniciclib plus chemotherapy (57.1%) than with placebo plus chemotherapy (38.6%).Conclusions
Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with extensive-disease SCLC, and the study was prematurely terminated. 相似文献6.
ROS1 Gene Rearrangements Are Associated With an Elevated Risk of Peridiagnosis Thromboembolic Events
Terry L. Ng Derek E. Smith Rao Mushtaq Tejas Patil Anastasios Dimou Shuo Yang Qian Liu Xuefei Li Caicun Zhou Robert T. Jones Megan M. Tu Flora Yan I. Alex Bowman Stephen V. Liu Siera Newkirk Joshua Bauml Robert C. Doebele Dara L. Aisner D. Ross Camidge 《Journal of thoracic oncology》2019,14(4):596-605
Introduction
This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate.Methods
Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002–April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers.Results
Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31–4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26–5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group.Conclusions
The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC. 相似文献7.
8.
Vinicius Ernani Adams Kusi Appiah Alissa Marr Chi Zhang Weining Zhen Lynette M. Smith Apar Kishor Ganti 《Journal of thoracic oncology》2019,14(3):475-481
Introduction
Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting.Methods
Patients (≥18 years) diagnosed with clinical stages I-II NSCLC from 2004 to 2013 were identified using the National Cancer Database (n = 11,836). The Kaplan-Meier method was used to estimate overall survival (OS) distributions and the log-rank test was used to compare distributions by treatment strategy. Clinical stages I and II were subdivided according to the TNM staging and log-rank tests was used to compare survival distributions by treatment strategy within each subgroup.Results
In patients with T2bN0, median OS in the SBRT alone and SBRT plus adjuvant chemotherapy groups were 16.5 months versus 24.2 months, respectively (95% confidence interval [CI]: 14.1–20.1 months and 18.8–33.3 months, respectively; p < .001); whereas for T3N0, median OS times were 13 months and 20.1 months, respectively (95% CI: 11.7–14.5 mohths and 17.7–21.9 months, respectively; p < .001). For tumors 4 cm or larger and node-negative disease, median OS was 15.9 months in the SBRT-alone group, and 19 months in the SBRT-plus-chemotherapy group (95% CI: 15.1–16.8 months and 17.9–20.8 months, respectively; p < .001). For patients with tumors less than 4 cm and node-negative disease, the median OS was 28.5 months in the SBRT-alone group and 24.3 months in the SBRT-plus-chemotherapy group (95% CI: 27.4–29.4 months and 22.8–26.1 months, respectively; p < .001).Conclusions
SBRT followed by adjuvant chemotherapy was associated with improved OS in comparison with SBRT alone in patients with T greater than or equal to 4 cm, similar to that seen after surgery. 相似文献9.
Rowena Yip Teng Ma Raja M. Flores David Yankelevitz Claudia I. Henschke 《Journal of thoracic oncology》2019,14(5):890-902
Objective
To determine long-term survival of visceral pleural invasion (VPI) and parenchymal invasion (PAI) (angiolymphatic and/or vascular) on survival of NSCLCs less than 30 mm in maximum diameter.Methods
Kaplan-Meier survivals for NSCLCs, with and without VPI and/or PAI, were determined for a prospective cohort of screening participants stratified by pathologic tumor size (≤10 mm, 11–20 mm, and 21–30 mm) and nodule consistency. Log-rank test statistics were calculated.Results
The frequency of PAI versus VPI was significantly lower in patients with subsolid nodules than in those with solid nodules (4.9% versus 27.7% [p < 0.0001]), and correspondingly, Kaplan-Meier lung cancer survival was significantly higher among patients with subsolid nodules (99.1% versus 91.3% [p = 0.0009]). Multivariable Cox regression found that only tumor diameter (adjusted hazard ratio [HR] =1.07, 95% confidence interval [CI]: 1.01–1.14, p = 0.02) and PAI (adjusted HR = 3.15, 95% CI: 1.25–7.90, p = 0.01) remained significant, whereas VPI was not significant (p = 0.15). When clinical and computed tomography findings were included with the pathologic findings, Cox regression showed that the risk of dying of lung cancer increased 10-fold (HR = 10.06, 95% CI: 1.35–75.30) for NSCLCs in patients with solid nodules and more than twofold (by a factor of 2.27) in patients with moderate to severe emphysema (HR = 2.27, 95% CI: 1.01–5.11), as well as with increasing tumor diameter (HR = 1.06, 95% CI: 1.01–1.13), whereas PAI was no longer significant (p = 0.19).Conclusions
Nodule consistency on computed tomography was a more significant prognostic indicator than either PAI or VPI. We propose that patients with NSCLC with VPI and a maximum tumor diameter of 30 mm or less not be upstaged to T2 without further large, multicenter studies of NSCLCs, stratified by the new T status and that classification be considered separately for patients with subsolid or solid nodules. 相似文献10.
Purpose
This study aimed to determine the pain response rates after conventional radiation therapy (RT) for painful bone metastases in prospective nonrandomized studies, which better reflect daily practice than randomized controlled trials.Methods and materials
A literature search was conducted in PubMed and Scopus for articles published between 2002 and 2018. We only included articles in which pain response after RT was assessed using the International Consensus Endpoint initially published in 2002, or the updated version from 2012. In addition, to be included in this review, the study design was required to be prospective or based on prospectively collected data. Our primary outcomes of interest were the overall and complete response rates after conventional RT for bone metastases.Results
Of the 2863 articles identified in our database search, 12 met the inclusion criteria. Six studies excluded patients with features of complicated bone metastases. Only 2 papers reported exclusion criteria regarding analgesic use. Radiation schedules that were frequently used were 1 × 8 Gy, 5 × 4 Gy, and 10 × 3 Gy. The overall response rate in evaluable patients was 55%, and 754 of the 1379 evaluable patients experienced a complete or partial response. The complete response rate was 15% (196 of 1348 evaluable patients). In the intent-to-treat patient group, the overall response rate was 29% (754 of 2559 enrolled patients), and the complete response rate 8% (196 of 2528 enrolled patients).Conclusions
We determined the pain response rates after conventional RT for painful bone metastases in prospective nonrandomized studies. The present review may provide benchmarks for future nonrandomized studies that investigate palliative RT for bone metastases. 相似文献11.
Chien-Hua Tseng Ben-Jei Tsuang Chun-Ju Chiang Kai-Chen Ku Jeng-Sen Tseng Tsung-Ying Yang Kuo-Hsuan Hsu Kun-Chieh Chen Sung-Liang Yu Wen-Chung Lee Tsang-Wu Liu Chang-Chuan Chan Gee-Chen Chang 《Journal of thoracic oncology》2019,14(5):784-792
Introduction
For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM2.5) levels on LC in Taiwan, in relation to contrasting PM2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).Methods
We reviewed 371,084 patients with LC to assess smoking prevalence and correlations between the incidence of adenocarcinoma lung cancer (AdLC) and non-AdLC. Two subsets were selected to assess different AdLC stage trends and the effect of PM2.5 on survival of patients with AdLC.Results
From 1995 to 2015, the proportion of male adult ever-smokers decreased from 59.4% to 29.9% whereas the female smoking rate remained low (3.2% to 5.3%). AdLC incidence in males and females increased from 9.06 to 23.25 and 7.05 to 24.22 per 100,000 population, respectively. Since 1993, atmospheric visibility in NT improved (from 7.6 to 11.5 km), but deteriorated in ST (from 16.3 to 4.2 km). The annual percent change in AdLC stages IB to IV was 0.3% since 2009 (95% confidence interval [CI]: -1.9%–2.6%) in NT, and 4.6% since 2007 (95% CI: 3.3%–5.8%) in ST; 53% patients with LC had never smoked. Five-year survival rates for never-smokers, those with EGFR wild-type genes, and female patients with AdLC were 12.6% in NT and 4.5% in ST (hazard ratio: 0.79, 95% CI: 0.70–0.90).Conclusions
In Taiwan, greater than 50% of patients with LC had never smoked. PM2.5 level changes can affect AdLC incidence and patient survival. 相似文献12.
Chao Zhang Shao-lei Li Qiang Nie Song Dong Yang Shao Xue-ning Yang Yi-long Wu Yue Yang Wen-zhao Zhong 《Journal of thoracic oncology》2019,14(4):726-731
Background
Locally advanced NSCLC is one of the most heterogeneous conditions, with multidimensional treatments involved. Neoadjuvant therapy had been commonly considered an optimal management strategy for patients with operable locally advanced. However, as targeted therapy has been widely applied in advanced NSCLC, neoadjuvant targeted therapy has remained poorly explored in locally advanced disease.Methods
We have described 11 ALK receptor tyrosine kinase gene (ALK)-positive patients with pathologically confirmed N2 NSCLC who were treated with neoadjuvant crizotinib. All the patients were treatment naive and received crizotinib at a starting dose of 250 mg twice daily. Patient 3 was provided with dynamic monitoring before and after neoadjuvant therapy through next-generation sequencing of plasma and tissue. In case 4, next-generation sequencing of preoperative tissue was performed.Results
Of the 11 patients, 10 had a partial response and one was stable disease after neoadjuvant crizotinib, with one suffering from grade 4 hepatic damage. Of the 11 patients, 10 (91.0%) received an R0 resection and 2 patients achieved a pathological complete response to neoadjuvant crizotinib. Six patients had disease recurrence, with five of them receiving crizotinib as first-line treatment and achieving a long duration of response. Dynamic monitoring of both plasma and tissue simultaneously indicated a decrease in sensitive ALK signaling in patient 3 and a partial response (approximately 50% of partial response), and no ALK-dependent resistance variants were captured.Conclusion
Neoadjuvant crizotinib may be feasible and well tolerated in locally advanced disease for complete resection. Crizotinib therapy before surgery may provide thorough elimination of circulating molecular residual disease and not influence the reuse of first-line crizotinib, but ongoing prospective trials are warranted to prove its efficacy in the neoadjuvant setting. 相似文献13.
Chen Suo Yajun Yang Ziyu Yuan Tiejun Zhang Xiaorong Yang Tao Qing Pei Gao Leming Shi Min Fan Hongwei Cheng Ming Lu Li Jin Xingdong Chen Weimin Ye 《Journal of thoracic oncology》2019,14(4):712-725
Introduction
Studies have reported alcohol consumption and genetic variants as major contributing factors for esophageal squamous cell carcinoma (ESCC). However, the complicated interactions between alcohol and genetic factors involved in alcohol metabolism have not been well elucidated with respect to augmented risk of ESCC.Methods
We performed a large population-based case-control study in a Chinese city with a high ESCC incidence by enrolling 1190 case patients and 1883 controls. We integrated candidate single-nucleotide polymorphism data, detailed alcohol consumption records, gene-alcohol interactions, and single-nucleotide polymorphism functional information to untangle the complicated relationship between alcohol, variants of genes encoding alcohol metabolism enzymes, and ESCC risk. The gene-alcohol interaction was tested by including their product term in a multivariable logistic regression model. Synergy index and ratio of ORs were calculated to assess interaction on additive and multiplicative scale, respectively.Results
We confirmed two ESCC susceptibility loci, rs671 in aldehyde dehydrogenase 2 family member gene (ALDH2) and rs1042026 in alcohol dehydrogenase 1B (class I), beta polypeptide gene (ADH1B), that significantly altered alcohol consumption behavior and subsequently modified the association between alcohol consumption and ESCC risk. The rs671(A) allele was associated with ESCC risk in alcohol drinkers (adjusted odds ratio =1.98, 95% confidence interval [CI]: 1.51–2.60) but not in nondrinkers. Healthy individuals who carry different ALDH2 and ADH1B genotypes exhibit diversified drinking behavior, with the proportion of drinkers varying between 23.7% and 54.3%. Among individuals with a fast ethanol oxidization rate, we observed a strong interaction between heavy alcohol consumption and ethanal oxidization rate on both the additive scale (synergy index 4.80 [95% CI: 1.82–12.68]) and the multiplicative scale (ratio of ORs 2.93, 95% CI: 1.39–6.35).Conclusions
Our observation highlights the need for preventing excessive use of alcohol, especially in individuals harboring active alcohol dehyrogenase and inactive ALDH2 variants. 相似文献14.
Ting Ye Lin Deng Shengping Wang Jiaqing Xiang Yawei Zhang Hong Hu Yihua Sun Yuan Li Lei Shen Li Xie Wenchao Gu Yue Zhao Fangqiu Fu Weijun Peng Haiquan Chen 《Journal of thoracic oncology》2019,14(4):617-627
Introduction
The clinicopathologic features and prognostic predictors of radiological part-solid lung adenocarcinomas were unclear.Methods
We retrospectively compared the clinicopathologic features and survival times of part-solid tumors with those of pure ground glass nodules (pGGNs) and pure solid tumors treated with surgery at Fudan University Shanghai Cancer Center and evaluated the prognostic implications of consolidation-to-tumor ratio (CTR), solid component size, and tumor size for part-solid lung adenocarcinomas.Results
A total of 911 patients and 988 pulmonary nodules (including 329 part-solid nodules [PSNs], 501 pGGNs, and 158 pure solid nodules) were analyzed. More female patients (p = 0.015) and nonsmokers (p = 0.003) were seen with PSNs than with pure solid nodules. The prevalence of lymphatic metastasis was lower in patients with PSNs than in those with pure solid tumors (2.2% versus 27% [p < 0.001]). The 5-year lung cancer–specific (LCS) recurrence-free survival and LCS overall survival of patients with PSNs were worse than those of patients with pGGNs (p < 0.001 and p = .042, respectively) but better than those of patients with pure solid tumors ([p < 0.001 and p < 0.0001, respectively]). CTR (OR = 12.90; 95% confidence interval [CI]: 1.85–90.04), solid component size (OR = 1.45; 95% CI: 1.28–1.64), and tumor size (OR = 1.23; 95% CI: 1.15–1.31) could predict pathologic invasive adenocarcinoma for patients with PSNs. None of them could predict the prognosis. Patients receiving sublobar resection had prognoses comparable to those of patients receiving lobectomy (p = .178 for 5-year LCS recurrence-free survival and p = .319 for 5-year LCS overall survival). The prognostic differences between patients with systemic lymph node dissection and those without systemic lymph node dissection were statistically insignificant.Conclusions
Part-solid lung adenocarcinoma showed clinicopathologic features different from those of pure solid tumor. CTR, solid component size, and tumor size could not predict the prognosis. Part-solid lung adenocarcinomas define one special clinical subtype. 相似文献15.
Zabi Wardak Alana Christie Alex Bowman Strahinja Stojadinovic Lucien Nedzi Sam Barnett Toral Patel Bruce Mickey Tony Whitworth Raquibul Hannan James Brugarolas Robert Timmerman 《Clinical genitourinary cancer》2019,17(2):e273-e280
Background
Brain metastases (BM) pose a significant problem in patients with metastatic renal-cell carcinoma (mRCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.Patients and Methods
The mRCC patients with BM treated with SRS were reviewed. Patient demographics, clinical history, and SRS treatment parameters were identified.Results
Among 268 patients with mRCC treated between 2006 and 2015, 38 patients were identified with BM. A total of 243 BM were treated with SRS with 1 to 26 BMs treated per SRS session (median, 2 BMs). The median (range) BM size was 0.6 (0.2-3.1) cm and median (range) SRS treatment dose was 18 (12-24) Gy. Treated BM local control rates at 1 and 2 years were 91.8% (95% confidence interval, 85.7-95.4) and 86.1% (95% confidence interval, 77.1-91.7), respectively. BM control declined for larger tumors. Survival after 1-year was 57.5% (95% CI 40.2-71.4) for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM. Survival was prognostic based on International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups in patients with < 5 BM. Two patients experienced grade 3 radiation necrosis requiring surgical intervention.Conclusion
SRS is effective in controlling BM in patients with mRCC. Over half of treated patients survive past a year, and no differences in survival were noted in patients with > 5 metastases. Prognostic risk categories based on systemic disease (IMDC) are predictive of survival in this BM population, with limited rates of symptomatic radiation necrosis. 相似文献16.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献17.
Song-Tao Xu Jun-Jie Xi Wen-Zhao Zhong Wei-Min Mao Lin Wu Yi Shen Yong-Yu Liu Chun Chen Ying Cheng Lin Xu Jun Wang Ke Fei Xiao-Fei Li Jian Li Cheng Huang Zhi-Dong Liu Shun Xu Ke-Neng Chen Yi-Long Wu 《Journal of thoracic oncology》2019,14(3):503-512
Introduction
Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized.Methods
Overall, 222 stage N1–N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted.Results
There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib.Conclusions
Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1–N2 EGFR-mutant NSCLC but longer duration should be explored. 相似文献18.
K.A. Lee M.T.A. Sharabiani D. Tumino J. Wadsley V. Gill G. Gerrard R. Sindhu M.N. Gaze L. Moss K. Newbold 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(6):385-390
Aims
To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series.Materials and methods
Six centres submitted data extracted from historical records on patients aged 18 years or younger, diagnosed between 1964 and 2017. The univariate and multivariable Cox proportional hazard model was used to identify potential predictors of progression-free survival, using national data as a control.Results
Data on 166 patients were available for analysis. Females (74%) were predominant, and the age ranged from 3 to 19 years at diagnosis, mean 14.1 years. Nodal metastases were present in 51%; 12% had distant metastases. After surgery, 95% received radioactive iodine (39% on more than one occasion) and 4% received external beam radiotherapy. With a median follow-up duration of 5 years, 69% are alive with no evidence of disease; 20% are alive with a raised thyroglobulin level as the only evidence of residual disease; 6% have residual structural disease detectable on imaging; 2% have died, from cerebral metastases.Conclusion
Despite most patients having advanced disease at presentation, outcomes are very good. A national prospective registry should allow systematic collection of good-quality data and may facilitate research to further improve outcomes. 相似文献19.
Suzanne B. Merrill Brian S. Sohl Ashiya Hamirani Erik B. Lehman Kathleen K. Lehman Matthew G. Kaag Jay D. Raman 《Clinical genitourinary cancer》2019,17(2):132-138
Introduction
The purpose of this study was to explore whether the practice of postoperative renal cell carcinoma (RCC) surveillance affords a survival benefit by investigating whether detection of RCC recurrences in an asymptomatic versus symptomatic manner influences mortality.Patients and Methods
We identified 737 patients who underwent partial or radical nephrectomy for M0 RCC between 1998 and 2016. Overall survival and disease-specific survival stratified by the type of recurrence detection (asymptomatic vs. symptomatic) was estimated using Kaplan-Meier probabilities both from the time of surgery and from the time of recurrence. Cox proportional hazard regression models were used to evaluate the impact of the type of recurrence detection on mortality.Results
A total of 78 patients (10.6%) experienced recurrence after surgery, of whom 63 (80.8%) were asymptomatic (detected using routine surveillance) and 15 (19.2%) were symptomatic. The median postoperative follow-up was 47.2 months (interquartile range, 26.3-89.4 months). Five- and 10-year overall survival, from time of surgery, among patients with asymptomatic versus symptomatic recurrences was 57% and 39% versus 24% and 8%, respectively (P = .0002). As compared with asymptomatic recurrences, patients with symptomatic recurrences had an increased risk of overall (OD) and disease-specific death (DSD) both when examined from the time of surgery (OD: hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.33-7.49; P = .0091 and DSD: HR, 3.44; 95% CI, 1.38-8.57; P = .0079) and from the time of recurrence (OD: HR, 2.93; 95% CI, 1.24-6.93; P = .0143 and DSD: HR, 3.62; 95% CI, 1.45-9.01; P = .0058).Conclusions
Capturing RCC recurrences in an asymptomatic manner during routine surveillance is associated with improved patient survival. 相似文献20.
Marianne Grønlie Guren Bjarte Aagnes Mari Nygård Olav Dahl Bjørn Møller 《Clinical colorectal cancer》2019,18(1):e96-e103