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1.
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2.
Daichi Fujimoto Hiroshige Yoshioka Yuki Kataoka Takeshi Morimoto Tae Hata Young Hak Kim Keisuke Tomii Tadashi Ishida Masataka Hirabayashi Satoshi Hara Manabu Ishitoko Yasushi Fukuda Moon Hee Hwang Naoki Sakai Motonari Fukui Hitoshi Nakaji Mitsunori Morita Tadashi Mio Toyohiro Hirai 《Journal of thoracic oncology》2019,14(3):468-474
Introduction
Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression.Methods
We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors–defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors–defined second progressive disease or death.Results
Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001).Conclusions
Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression. 相似文献3.
Morgan R.L. Lichtenstein Ryan D. Nipp Alona Muzikansky Kelly Goodwin Danyon Anderson Richard A. Newcomb Justin F. Gainor 《Journal of thoracic oncology》2019,14(3):547-552
Introduction
Immunotherapy has revolutionized the treatment of NSCLC, but little is known about the activity of programmed cell death 1 and programmed death ligand 1 blockade across age groups.Methods
We retrospectively evaluated patients with NSCLC who initiated programmed cell death 1 and programmed death ligand 1 inhibitors from January 2013 through July 2017. Medical records and radiographic imaging were reviewed to determine progression-free survival (PFS) and overall survival (OS). We also compared immunotherapy-related toxicities, steroid use, and hospitalizations by age.Results
Of the 245 patients, 26.1% were younger than 60 years, 31.4% were age 60 to 69 years, 31.0% were age 70 to 79 years, and 11.4% were age 80 years or older. The median PFS times by age group were as follows: younger than 60 years, 1.81 months; age 60 to 69 years, 2.53 months; age 70 to 79 years, 3.75 months; and age 80 years or older, 1.64 months (log-rank p value = 0.055). The median OS times by age group were as follows: younger than 60 years, 13.01 months; age 60 to 69 years, 14.56 months; age 70 to 79 years, 12.92 months; and age 80 years or older, 3.62 months (log-rank p value = 0.011). Rates of immunotherapy-related toxicities, steroid use, and hospitalizations did not differ by age.Conclusions
Although the OS and PFS benefits of immunotherapy differ by age, the rates of toxicity are similar regardless of age. 相似文献4.
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5.
Yang Qu Katsura Emoto Takashi Eguchi Rania G. Aly Hua Zheng Jamie E. Chaft Kay See Tan David R. Jones Mark G. Kris Prasad S. Adusumilli William D. Travis 《Journal of thoracic oncology》2019,14(3):482-493
Introduction
Major pathologic response after neoadjuvant chemotherapy (NAC) for NSCLC has been defined as 10% or less residual viable tumor without distinguishing between histologic types. We sought to investigate whether the optimal cutoff percentage of residual viable tumor for predicting survival differs between lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC).Methods
Tumor slides from 272 patients treated with NAC and surgery for clinical stage II-III NSCLC (ADC, n = 192; SCC, n = 80) were reviewed. The optimal cutoff percentage of viable tumor for predicting lung cancer–specific cumulative incidence of death (LC-CID) was determined using maximally selected rank statistics. LC-CID was analyzed using a competing-risks approach. Overall survival was evaluated using Kaplan-Meier methods and Cox proportional hazard analysis.Results
Patients with SCC had a better response to NAC (median percentage of viable tumor: SCC versus ADC, 40% versus 60%; p = 0.027). Major pathologic response (≤10% viable tumor) was observed in 26% of SCC cases versus 12% of ADC cases (p = 0.004). The optimal cutoff percentage of viable tumor for LC-CID was 10% for SCC and 65% for ADC. On multivariable analysis, viable tumor 10% or less was an independent factor for better LC-CID (p = 0.035) in patients with SCC; in patients with ADC, viable tumor 65% or less was a factor for better LC-CID (p = 0.033) and overall survival (p = 0.050).Conclusions
In response to NAC, the optimal cutoff percentage of viable tumor for predicting survival differs between ADC and SCC. Our findings have implications for the pathologic assessment of resected specimens, especially in upcoming clinical trials design. 相似文献6.
Fabrice Barlesi Edward B. Garon Dong-Wan Kim Enriqueta Felip Ji-Youn Han Joo-Hang Kim Myung-Ju Ahn Mary Jo Fidler Matthew A. Gubens Gilberto de Castro Veerle Surmont Qiao Li Anne C. Deitz Gregory M. Lubiniecki Roy S. Herbst 《Journal of thoracic oncology》2019,14(5):793-801
Introduction
In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.Methods
Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.Results
Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.Conclusions
These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. 相似文献7.
Alp Tuna Beksac Mesude Bicak Ishan Paranjpe David J. Paulucci John P. Sfakianos Ketan K. Badani 《Clinical genitourinary cancer》2019,17(2):e314-e322
Background
Chromophobe renal cell carcinoma (chRCC) is known as an indolent tumor; however, mortality still occurs. We sought to determine the clinicopathologic and genomic factors associated with aggressive chRCC.Patients and Methods
Two different datasets were used to identify patients with clinical stage III and IV chRCC. Eighteen patients from The Cancer Genome Atlas (TCGA) database and 1693 patients from the American College of Surgeons National Cancer Database (NCDB) were used for analysis. From the TCGA, RNA-Seq expression analysis of 18,745 genes was conducted between the recurrent (n = 5; 27.8%) and nonrecurrent patients (n = 13; 72.2%). Biological significance was identified via pathway enrichment and gene function analyses. From the NCDB, Cox proportion hazards regression models were used to identify variables associated with overall survival (OS) at a median follow-up of 41.4 months.Results
Between the 2 groups, 2182 genes were differentially expressed. The most commonly overexpressed pathways were neuroactive ligand-receptor interactions and cytokine-cytokine receptor interactions. The most activated gene functions were cellular, metabolic, and multicellular organismal processes. In the NCDB, multivariable analysis, age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03-1.05; P < .001), TNM stage IV versus III (HR, 3.86; 95% CI, 2.98-5.00; P < .001), and positive surgical margin (HR, 1.68; 95% CI, 1.45-1.96; P < .001) were associated with worse OS at a median follow-up of 41.4 months. Five-year OS was significantly lower for stage IV patients compared with stage III patients (80.0% vs. 29.9%; P < .001).Conclusions
Patients with recurrent chRCC demonstrated a differential gene expression of specific biochemical pathways. Clinical parameters associated with worse OS included age, stage, and positive surgical margin. 相似文献8.
Kurtis D. Davies Aprille Lomboy Carolyn A. Lawrence Michael Yourshaw Gregary T. Bocsi D. Ross Camidge Dara L. Aisner 《Journal of thoracic oncology》2019,14(4):737-741
Introduction
Genomic variants that lead to MET proto-oncogenem receptor tyrosine kinase (MET) exon 14 skipping represent a potential targetable molecular abnormality in NSCLC. Consequently, reliable molecular diagnostic approaches that detect these variants are vital for patient care.Methods
We screened tumor samples from patients with NSCLC for MET exon 14 skipping by using two distinct approaches: a DNA-based next-generation sequencing assay that uses an amplicon-mediated target enrichment and an RNA-based next-generation sequencing assay that uses anchored multiplex polymerase chain reaction for target enrichment.Results
The DNA-based approach detected MET exon 14 skipping variants in 11 of 856 NSCLC samples (1.3%). The RNA-based approach detected MET exon 14 skipping in 17 of 404 samples (4.2%), which was a statistically significant increase compared with the DNA-based assay. Among 286 samples tested by both assays, RNA-based testing detected 10 positives, six of which were not detected by the DNA-based assay. Examination of primer binding sites in the DNA-based assay in comparison with published MET exon 14 skipping variants revealed genomic deletion involving primer binding sequences as the likely cause of false negatives. Two samples positive via the DNA-based approach were uninformative via the RNA-based approach due to poor-quality RNA.Conclusions
By circumventing an inherent limitation of DNA-based amplicon-mediated testing, RNA-based analysis detected a higher proportion of MET exon 14 skipping cases. However, RNA-based analysis was highly reliant on RNA quality, which can be suboptimal in some clinical samples. 相似文献9.
10.
J. Connor Wells Dongsheng Tu Lillian L. Siu Jeremy D. Shapiro Derek J. Jonker Christos Karapetis John Simes Geoffrey Liu Timothy J. Price Niall C. Tebbutt Chris J. O’Callaghan 《Clinical colorectal cancer》2019,18(1):e140-e149
Background
The safety and efficacy of targeted therapy in older patients (≥ 70 years) with metastatic colorectal cancer is not well evaluated.Patients and Methods
Outcomes of older patients (including overall survival [OS], progression-free survival [PFS], toxicity, and quality of life [QoL]) were compared to young patients using data from 2 large previously reported clinical trials, CO.17 (cetuximab vs. best supportive care) and CO.20 (cetuximab plus placebo vs. cetuximab plus brivanib). Only patients with wild-type KRAS tumors were included.Results
A total of 251 (26.3%) of 955 patients were ≥ 70 years old. No significant differences in OS, PFS, or grade 3/4 adverse events were observed between older and younger patients treated with cetuximab (or cetuximab with placebo) in either trial. Younger patients trended toward superior OS in both CO.17 (hazard ratio = 1.80; P = .16) and CO.20 (hazard ratio = 1.34; P = .07). QoL maintenance favored younger patients in CO.17 (3.6 vs. 5.7 months; P = .046) but no difference of QoL maintenance was observed in the larger CO.20 trial (1.7 vs. 1.8 months; P = .64). Combination therapy of cetuximab and brivanib was significantly more toxic in older adults (87% vs. 77%; P = .03).Conclusion
OS, PFS, and toxicities were similar between older and younger patients with wild-type KRAS metastatic colorectal cancer when treated with cetuximab. Both age groups likely experience similar QoL maintenance with cetuximab. Dual targeted therapy was significantly more toxic in older patients. 相似文献11.
Purpose
To assess the pharmacologic costs of second-line treatments for metastatic renal-cell cancer (mRCC).Methods
The present evaluation was restricted to pivotal phase 3 randomized controlled trials in second-line for mRCC. We calculated the pharmacologic costs necessary to get the benefit in progression-free survival and overall survival (OS) for each trial. The costs of drugs are at the pharmacy of our hospital and are expressed in euros.Results
Our analysis evaluated 5 phase 3 randomized controlled trials including 3112 patients. The lowest cost per month of progression-free survival and OS gained was associated with the use of cabozantinib (€2006 and €1473, respectively), while everolimus had the highest cost per month of OS gained (€28,590).Conclusion
Combining pharmacologic costs of drugs with the measure of efficacy represented by OS, cabozantinib is a cost-effective second-line treatments for patients with mRCC. 相似文献12.
13.
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14.
Megan Greally Joanne F. Chou Daniela Molena Valerie W. Rusch Manjit S. Bains Bernard J. Park Abraham J. Wu Karyn A. Goodman David P. Kelsen Yelena Y. Janjigian David H. Ilson Geoffrey Y. Ku 《Journal of thoracic oncology》2019,14(3):540-546
Introduction
Preoperative or definitive chemoradiation is an accepted treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The MUNICON study showed that positron-emission tomography (PET) response following induction chemotherapy was predictive of outcomes in patients with gastroesophageal junction adenocarcinoma. We evaluated the predictive value of PET following induction chemotherapy in ESCC patients and assessed the impact of changing chemotherapy during radiation in PET nonresponders.Methods
We retrospectively reviewed all patients with locally advanced ESCC who received induction chemotherapy and chemoradiation; all patients had a PET before and after induction chemotherapy. Survival was calculated from date of repeat PET using Kaplan-Meier analysis and compared between groups using the log-rank test.Results
Of 111 patients, 70 (63%) were PET responders (defined as a 35% or more decrease in maximum standard uptake value) to induction chemotherapy. PET responders received the same chemotherapy during radiation. Of 41 PET nonresponders, 16 continued with the same chemotherapy and 25 were changed to alternative chemotherapy with radiation. Median progression-free survival (70.1 months versus 7.1 months, p < 0.01) and overall survival (84.8 months versus 17.2 months, p < 0.01) were improved for PET responders versus nonresponders. Median progression-free survival and overall survival for PET nonresponders who changed chemotherapy versus those who did not were 6.4 months versus 8.3 months (p = 0.556) and 14.1 versus 17.2 months (p = 0.81), respectively.Conclusions
PET after induction chemotherapy highly predicts for outcomes in ESCC patients who receive chemoradiation. However, our results suggest that PET nonresponders do not benefit from changing chemotherapy during radiation. Future trials should use PET nonresponse after induction chemotherapy to identify poor prognosis patients for novel therapies. 相似文献15.
Paola Morelato Assunção Tamires Prates Lana Márcia Torresan Delamain Gislaine Oliveira Duarte Roberto Zulli Irene Lorand-Metze Carmino Antonio de Souza Erich Vinicius de Paula Katia Borgia Barbosa Pagnano 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):162-166
Background
Cardiovascular events (CVEs) have been observed in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors.Patients and Methods
We retrospectively evaluated the incidence of CVEs on 233 consecutive patients with chronic myeloid leukemia, of which 116 were treated with imatinib, 75 with dasatinib, and 42 with nilotinib. The median follow-up was 2047, 1712, and 1773 days, respectively.Results
The cumulative incidence of CVEs was 4.29%. Three events occurred during dasatinib treatment, 6 during nilotinib treatment, and none during imatinib treatment (P ≤ .001). Arterial occlusive events occurred in 2 (2.6%) of 75 patients treated with dasatinib and in 6 (14.2%) of 42 patients treated with nilotinib (P ≤ .001). Furthermore, all of them occurred in patients with high-risk (n = 2) and very high-risk (n = 6) cardiovascular risk, contributing to 4.3% of mortality.Conclusion
CVEs were more frequent in patients treated with second-generation tyrosine kinase inhibitors. Arterial occlusive events were more frequent in patients treated with nilotinib, with high and very high cardiovascular risk. 相似文献16.
Ieva Kurilova Regina G.H. Beets-Tan Jessica Flynn Mithat Gönen Gary Ulaner Elena N. Petre F. Edward Boas Etay Ziv Hooman Yarmohammadi Elisabeth G. Klompenhouwer Andrea Cercek Nancy A. Kemeny Constantinos T. Sofocleous 《Clinical colorectal cancer》2019,18(1):8-18
Introduction
The purpose of this study was to identify predictors of overall (OS) and liver progression-free survival (LPFS) following Yttrium-90 radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM), as well as to create and validate a predictive nomogram for OS.Materials and Methods
Metabolic, anatomic, laboratory, pathologic, genetic, primary disease, and procedure-related factors, as well as pre- and post-RAE therapies in 103 patients with CLM treated with RAE from September 15, 2009 to March 21, 2017 were analyzed. LPFS was defined by Response Evaluation Criteria In Solid Tumors 1.1 and European Organization for Research and Treatment of Cancer criteria. Prognosticators of OS and LPFS were selected using univariate Cox regression, adjusted for clustering and competing risk analysis (for LPFS), and subsequently tested in multivariate analysis (MVA). The nomogram was built using R statistical software and internally validated using bootstrap resampling.Results
Patients received RAE at a median of 30.9 months (range, 3.4-161.7 months) after detection of CLM. The median OS and LPFS were 11.3 months (95% confidence interval, 7.9-15.1 months) and 4 months (95% confidence interval, 3.3-4.8 months), respectively. Of the 40 parameters tested, 6 were independently associated with OS in MVA. These baseline parameters included number of extrahepatic disease sites (P < .001), carcinoembryonic antigen (P < .001), albumin (P = .005), alanine aminotransferase level (P < .001), tumor differentiation level (P < .001), and the sum of the 2 largest tumor diameters (P < .001). The 1-year OS of patients with total points of < 25 versus > 80 was 90% and 10%, respectively. Bootstrap resampling showed good discrimination (optimism corrected c-index = 0.745) and calibration (mean absolute prediction error = 0.299) of the nomogram. Only baseline maximum standardized uptake value was significant in MVA for LPFS prediction (P < .001; SHR = 1.06).Conclusion
The developed nomogram included 6 pre-RAE parameters and provided good prediction of survival post-RAE in heavily pretreated patients. Baseline maximum standardized uptake value was the single significant predictor of LPFS. 相似文献17.
Michiel A. IJsseldijk Melina Shoni Charles Siegert Bastiaan Wiering K.C. Anton van Engelenburg Abraham Lebenthal Richard P.G. ten Broek 《Journal of thoracic oncology》2019,14(4):583-595
Introduction
Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC.Methods
The main databases were searched for trials and cohort studies without restrictions to publication status or language. Two independent researchers performed the screening and selection of eligible studies. Outcomes were overall survival, cancer-specific survival, and disease-free survival. The inverse variance method and the random effects method for meta-analysis were used to assess pooled survival estimates.Results
A total of 11,195 nonduplicate records were identified by the original search strategy. After screening by title and abstract, 1051 potentially eligible records were identified. A total of 43 articles were included. The comparative studies showed lower 3-year overall survival and lower 2-year and 5-year cancer-specific survival for biopsy-proven disease compared to clinical disease. However, 5-year overall survival was the same for both groups. For the pooled estimates, 3-year disease-free survival and 2-year cancer-specific survival were lower for biopsied disease.Conclusions
Results of this systematic review and meta-analysis show a discrepancy in oncological outcomes for patients undergoing SBRT for suspected early-stage NSCLC in whom there is pathologic conformation of malignancy and those who there is only a clinical diagnose of NSCLC. These results emphasize the importance of obtaining pathologic proof of malignancy. 相似文献18.
James Chih-Hsin Yang Shirish M. Gadgeel Lecia VanDam Sequist Chien-Liang Wu Vassiliki A. Papadimitrakopoulou Wu-Chou Su Joseph Fiore Sanatan Saraf Harry Raftopoulos Amita Patnaik 《Journal of thoracic oncology》2019,14(3):553-559
Introduction
Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with the anti–programmed death 1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 study (NCT02039674).Methods
Adults with previously untreated stage IIIB/IV EGFR-mutant NSCLC were treated with pembrolizumab 2 mg/kg intravenously every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3 + 3 design with cohort expansion. rTumor response was evaluated per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review. The primary objective was determination of a recommended phase 2 dose.Results
Twelve patients enrolled to receive pembrolizumab plus erlotinib and seven to receive pembrolizumab plus gefitinib. No dose-limiting toxicities or grade 5 events occurred. Pembrolizumab plus erlotinib was feasible, with adverse events similar to those expected for monotherapy. However, pembrolizumab plus gefitinib was not feasible due to grade 3/4 liver toxicity in five of seven patients (71.4%), leading to permanent treatment discontinuation in four patients. The most frequently occurring treatment-related adverse events with pembrolizumab plus erlotinib were rash (50.0%), dermatitis acneiform, diarrhea, hypothyroidism, and pruritus (33.3% each). The objective response rate was 41.7%, including response in all four patients with programmed death ligand 1 expression 50% or greater.Conclusions
Although pembrolizumab plus gefitinib was not feasible, the toxicity profile observed with pembrolizumab plus erlotinib suggests combining immunotherapy with anti-EGFR therapy is feasible. Pembrolizumab plus erlotinib did not improve objective response rate compared with previous monotherapy studies; further evaluation would be necessary to evaluate potential effects on other efficacy 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.
Rajni Sethi Jyoti Mayadev Suresh Sethi Dominique Rash Lee-may Chen Rebecca Brooks Stefanie Ueda I-Chow Hsu 《Practical radiation oncology》2019,9(2):e180-e186