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1.
Marco Maruzzo Umberto Basso Eugenio Borsatti Laura Evangelista Filippo Alongi Orazio Caffo Francesca Maines Sara Galuppo Rocco De Vivo Fable Zustovich Dario Palleschi Andrea Zivi Teodoro Sava Mariella Sorarù Roberto Iacovelli Maurizio Nicodemo Susanne Baier Lucia Fratino Vittorina Zagonel 《Clinical genitourinary cancer》2019,17(1):e187-e194
Background
Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.Patients and Methods
We conducted a multicenter retrospective analysis in the Triveneto region of Italy.Results
One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.Conclusion
This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined. 相似文献2.
Caitlin A. Schonewolf Marina Heskel Abigail Doucette Sunil Singhal Melissa A. Frick Eric P. Xanthopoulos Michael N. Corradetti Joseph S. Friedberg Taine T. Pechet John P. Christodouleas William Levin Abigail Berman Keith A. Cengel Vivek Verma Stephen M. Hahn John C. Kucharczuk Ramesh Rengan Charles B. Simone 《Clinical lung cancer》2019,20(1):e63-e71
Background
Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non–small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients.Patients and Methods
All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression.Results
A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes.Conclusions
SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities. 相似文献3.
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4.
Aleš Obr Vít Procházka Andrea Jirkuvová Helena Urbánková Eva Kriegova Petra Schneiderová Michaela Vatolíková Tomáš Papajík 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):762-768
Background
TP53 mutation (TP53mut) and a complex karyotype (CK) were shown to be predictors of poor outcome in mantle-cell lymphoma (MCL). In this study we examined the combined effect of both of these risk factors.Patients and Methods
Patients diagnosed with MCL between January 2000 and December 2014 (n = 74) were evaluated. Forty-eight of them had available material for TP53 and cytogenetic examination. We analyzed the prognostic effect of combined TP53mut and CK in the cohort of patients treated with rituximab-containing therapy.Results
Three-year (3-y) overall survival (OS) and 3-y progression-free survival (PFS) in CK patients were shorter compared with non-CK (P = .001 for OS; P = .02 for PFS). TP53mut was a predictor of shorter survival compared with TP53 wild type (OS and PFS; P < .001). The incidence of TP53mut was not significantly associated with CK (P = .240). CK and TP53mut were predictors of inferior PFS and OS independent of age and Mantle-Cell Lymphoma International Prognostic Index, with hazard ratios of 2.35 (P = .024), 4.50 (P < .001) for PFS and 4.31 (P < .001), 5.46 (P < .001) for OS analysis in the CK and TP53mut groups, respectively. The combination of TP53mut and CK status stratified the patients into 3 prognostic groups (P < .001) with the worst outcome in patients with CK and TP53mut.Conclusion
TP53 mutation and CK occurred independently and patients harboring both had a dismal prognosis. The study suggests the importance of molecular cytogenetics and examination of the TP53mut status to be performed simultaneously before treatment. 相似文献5.
Derek J. Jonker Patricia A. Tang Hagen Kennecke Stephen A. Welch M. Christine Cripps Timothy Asmis Haji Chalchal Anna Tomiak Howard Lim Yoo-Joung Ko Eric X. Chen Thierry Alcindor John R. Goffin Grzegorz J. Korpanty Harriet Feilotter Ming S. Tsao Ashley Theis Dongsheng Tu Lesley Seymour 《Clinical colorectal cancer》2018,17(3):231-239.e7
Background
Oncolytic reovirus pelareorep might preferentially infect and destroy rat sarcoma (RAS)-activated cells, and has preclinical and early clinical activity against colorectal cancer (CRC).Patients and Methods
After a 6-patient safety run-in, 103 patients with metastatic CRC were randomly assigned to standard first-line leucovorin/5-FU/oxaliplatin (FOLFOX6)/bevacizumab (FOLFOX/BEV) every 2 weeks with (n = 51) or without (n = 52) pelareorep 3 × 1010 tissue culture infective dose 50 on days 1 to 5 (cycles 1, 2, 4, and alternate cycles thereafter). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life, and correlative analyses.Results
At 13 months' median follow-up, PFS was inferior in the pelareorep arm (median 7 vs. 9 months; hazard ratio [HR], 1.59 [80% confidence interval (CI), 1.18-2.15]; P = .046). There was no statistical difference in OS (median, 19.2 vs. 20.1 months; HR, 1.22; P = .38). An increased ORR was observed with pelareorep (adjusted odds ratio, 2.52 [80% CI, 1.44-4.41]; P = .03), but with a shorter median duration of response (5 vs. 9 months; P = .028). Pelareorep patients experienced more hypertension and proteinuria, and were more likely to omit bevacizumab before progression. A trend to lower dose intensity and shorter oxaliplatin and bevacizumab treatment duration was observed with pelareorep.Conclusion
Combination pelareorep with FOLFOX/BEV was tolerable with an increased ORR, but PFS was inferior. Subgroup analysis of baseline variables including Kirsten rat sarcoma oncogene did not identify subgroups with PFS benefit. Decreased treatment intensity with standard agents likely contributed to the lack of benefit with pelareorep. Future studies might consider alternate pelareorep/chemotherapy strategies or combination therapy with novel agents. 相似文献6.
Roberto Mina Maria Teresa Petrucci Paolo Corradini Stefano Spada Francesca Patriarca Chiara Cerrato Lorenzo De Paoli Norbert Pescosta Roberto Ria Alessandra Malfitano Pellegrino Musto Luca Baldini Tommasina Guglielmelli Barbara Gamberi Donato Mannina Giulia Benevolo Renato Zambello Antonietta Pia Falcone Sara Bringhen 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(8):533-540
Background
High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy.Patients and Methods
We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m).Results
Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy.Conclusion
Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy. 相似文献7.
Won Kyung Cho Won Park Doo Ho Choi Yong Bae Kim Jin Ho Kim Su Ssan Kim Kyubo Kim Jin Hee Kim Sung Ja Ahn Sun Young Lee Jeongshim Lee Sang-Won Kim Jeanny Kwon Ki Jung Ahn 《Clinical breast cancer》2019,19(1):78-86
Background
Given the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status.Patients and Methods
We analyzed 261 patients who received NAC followed by BCS and adjuvant radiotherapy in 13 institutions of the Korean Radiation Oncology Group from 2005 to 2011. The tumors were classified into one of 3 subtypes: luminal (estrogen receptor positive or progesterone receptor positive and HER2 negative), HER2 (HER2 positive), or triple negative (estrogen receptor, progesterone receptor, and HER2 negative). We compared locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) according to ENI in different subgroups generated by the subtype and pCR statuses.Results
In all patients, the 5-year LRC, DFS, and OS rates were 96.0%, 91.0%, and 96.8%, respectively. In all patients, axillary lymph node dissection was found to be the only favorable factor for LRC (P = .023) and DFS (P = .001). Age ≥ 50 years (P = .027), negative resection margin (P = .002), and axillary lymph node dissection (P = .002) were all favorable factors for OS. ENI did not affect LRC, DFS, or OS. Subgroup analysis by tumor subtype and pCR showed that ENI was not associated with greater LRC or DFS in any subgroups.Conclusion
In ypN0 patients after NAC and BCS, ENI did not improve LRC or survival, regardless of subtype or primary tumor response. This result should be verified through larger prospective trials. 相似文献8.
Background
Progression-free survival (PFS) and time to progression (TTP) have been reported to correlate with overall survival (OS) in several cancer types. To our knowledge, however, the correlation between them is unclear.Methods
A literature-based meta-analysis was performed to assess whether PFS and TTP can be considered reliable surrogate end points for OS in a phase 3 clinical trial of advanced breast cancer (ABC). The median hazard ratios of PFS/TTP and OS were analyzed by determining their nonparametric Spearman rank correlation coefficients (Rs).Results
A total of 37 trials with 38 treatment arms and 14,966 patients were selected for analysis. The Rs between the median PFS/TTP and OS was 0.405 (95% confidence interval [CI], 0.191-0.582; P = .003), and the correlation coefficient between the hazard ratios of PFS/TTP and OS was 0.555 (95% CI, 0.277-0.748; P = .003). PFS/TTP was closely correlated with OS in the trials of targeted therapy-based treatment (Rs = 0.872; 95% CI, 0.619-0.962; P = .0001) and of PFS/TTP or OS benefit (Rs = 0.753 and Rs = 0.821, respectively) for ABC.Conclusions
Both PFS and TTP can be considered valid surrogate end points for OS in the trials of targeted therapy-based treatments and clinical benefits for ABC. Further research is necessary to clarify the surrogacy of PFS/TTP for OS in other trials of targeted therapy-based treatments for ABC. 相似文献9.
Nils Kroeger Haoran Li Guillermo De Velasco Frede Donskov Hao-Wen Sim Viktoria Stühler J. Connor Wells Igor Stukalin Johannes Heide Jens Bedke Neeraj Agarwal Hiral Parekh Brian I. Rini Jennifer J. Knox Allan Pantuck Toni K. Choueiri Daniel Yick Chin Heng 《Clinical genitourinary cancer》2019,17(1):65-71
Background
Smoking increases the risk of developing renal cell carcinoma (RCC) but the effect of tobacco consumption on survival outcome of patients with metastatic RCC (mRCC) treated with targeted therapies has not been well characterized.Patients and Methods
The primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). Patients with mRCC were categorized as current, former, and nonsmokers at the time of starting targeted therapy. Smoking data from 1980 patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium (IMDC) from 12 international cancer centers.Results
Although former and nonsmokers had comparable OS times (23.8 vs. 23.4 months; P = .898), current smokers had significantly shorter OS (16.1 months; P < .001) than nonsmokers. Current but not former smoking status was an independent poor prognosis factor (hazard ratio [HR], 1.3; P = .002) when adjusted for the IMDC risk criteria. Each pack-year increased the risk of death by 1% (HR, 1.01; P = .036). The duration of first-line therapy response was not different and was 7.7 months versus 7.5 months versus 6.4 months in never, former (P = .609), and current smokers (P = .839), respectively.Conclusion
Active smoking is associated with diminished OS in mRCC patients treated with targeted therapy agents. However, patients who quit smoking returned to a similar risk of death from RCC compared with patients who never smoked. Smoking cessation should be a counseling priority among mRCC patients receiving targeted agents and smoking should be considered as a confounding factor in major clinical trials. 相似文献10.
Sarah Buelens Tom Claeys Bert Dhondt Filip Poelaert Matthijs Vynck Nurten Yigit Olivier Thas Piet Ost Jo Vandesompele Nicolaas Lumen Candy Kumps 《Clinical genitourinary cancer》2018,16(3):197-205.e5
Background
Resistance mechanisms in the androgen receptor (AR) signaling pathway remain key drivers in the progression to castration-resistant prostate cancer (CRPC) and relapse under antihormonal therapy.Materials and Methods
We evaluated the circulating AR gene copy number (CN) gain using droplet digital polymerase chain reaction in 21 control and 91 prostate cancer serum samples and its prognostic and therapeutic implications in prostate cancer.Results
In CRPC, AR CN gain was associated with faster progression to CRPC (P = .026), a greater number of previous treatments (P = .045), and previous chemotherapy (P = .016). Comparing patients with and without CN gain, the median progression-free survival (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004), and the median overall survival (OS) was 7 months versus 20.9 months (P = .020). In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus 6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The presence of more AR copies correlated with shorter androgen deprivation (P = .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039) therapy.Conclusion
Circulating AR CN gain predicts for a poor prognosis in CRPC. It is a promising biomarker predetermining rapid CRPC progression and predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is associated with multiple previous treatments and previous chemotherapy. 相似文献11.
Enriqueta Felip Vera Hirsh Sanjay Popat Manuel Cobo Andrea Fülöp Charles Dayen José M. Trigo Richard Gregg Cornelius F. Waller Jean-Charles Soria Glenwood D. Goss James Gordon Bushi Wang Michael Palmer Eva Ehrnrooth Shirish M. Gadgeel 《Clinical lung cancer》2018,19(1):74-83.e11
Introduction
In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented.Patients and Methods
Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d). PROs were collected (baseline, every 28 days until progression, 28 days after discontinuation) using the European Organization for Research and Treatment of Cancer QoL questionnaire and lung cancer-specific module. The percentage of patients improved during therapy, time to deterioration (TTD), and changes over time were analyzed for prespecified lung cancer-related symptoms and global health status (GHS)/QoL.Results
Questionnaire compliance was 77.3% to 99.0% and 68.7% to 99.0% with afatinib and erlotinib, respectively. Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL (36% vs. 28%; P = .041) and cough (43% vs. 35%; P = .029). Afatinib significantly delayed TTD in dyspnea (P = .008) versus erlotinib, but not cough (P = .256) or pain (P = .869). Changes in mean scores favored afatinib for cough (P = .0022), dyspnea (P = .0007), pain (P = .0224), GHS/QoL (P = .0320), and all functional scales. Differences in adverse events between afatinib and erlotinib, specifically diarrhea, did not affect GHS/QoL.Conclusion
In patients with SCC of the lung, second-line afatinib was associated with improved prespecified disease-related symptoms and GHS/QoL versus erlotinib, complementing PFS and OS benefits with afatinib. 相似文献12.
13.
Kenji Tsuchihashi Mamoru Ito Toshikazu Moriwaki Shota Fukuoka Hiroya Taniguchi Atsuo Takashima Yosuke Kumekawa Takeshi Kajiwara Kentaro Yamazaki Taito Esaki Akitaka Makiyama Tadamichi Denda Hironaga Satake Takeshi Suto Naotoshi Sugimoto Kenji Katsumata Toshiaki Ishikawa Tomomi Kashiwada Eishi Baba 《Clinical colorectal cancer》2018,17(4):e687-e697
Background
Assessment of patient factors is essential for selecting later-line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated.Patients and Methods
A total of 550 patients with mCRC who were registered in the REGOTAS study (Regorafenib versus TAS-102 as Salvage-line in patients with colorectal cancer refractory to standard chemotherapies: a multicenter observational study, UMIN 000020416) and treated with trifluridine/tipiracil (TFTD) or regorafenib as a later-line therapy were retrospectively stratified according to the modified Glasgow Prognostic Score (mGPS), which divided patients into mGPS 0 to 2 by serum albumin and C-reactive protein, and compared.Results
The median overall survival (OS) of patients with mGPS 0, 1, and 2 was 10.0 months (95% confidence interval [CI], 9.2-11.6 months), 6.5 months (95% CI, 5.3-7.1 months), and 3.9 months (95% CI, 3.3-4.9 months), respectively. The median progression-free survival (PFS) with mGPS 0, 1, and 2 was 2.5 months (95% CI, 2.1-3.0 months), 2.0 months (95% CI, 1.9-2.3 months), and 1.7 months (95% CI, 1.4-1.9 months), respectively. There were significant differences by mGPS in both OS and PFS (all P < .001). No significant differences in OS and PFS were observed between the patient groups treated with TFTD and regorafenib in each mGPS group. In patients aged ≥ 65 years with mGPS 2, the OS and PFS were worse with regorafenib than with TFTD (OS: hazard ratio, 1.45; 95% CI, 0.93-2.25; P = .097; PFS: hazard ratio, 1.57, 95% CI, 1.01-2.44; P = .047), but there were no consistent trends observed as mGPS increased. The frequency of grade 3 and more adverse events was generally similar in each mGPS group. The multivariate analyses showed that mGPS was the strongest predictive factor for OS.Conclusions
The mGPS before later-line chemotherapy is strongly correlated with survival in patients with mCRC. 相似文献14.
Fang Hu Jianlin Xu Bo Zhang Changhui Li Wei Nie Ping Gu Ping Hu Huimin Wang Yujun Zhang Yinchen Shen Shuyuan Wang Xueyan Zhang 《Clinical lung cancer》2019,20(1):e81-e90
Background
For oligometastatic lung adenocarcinoma patients with sensitive epidermal growth factor receptor (EGFR) mutations, the role of local consolidative therapy (LCT) remains debatable. The purpose of this study was to investigate the efficacy of LCT in oligometastatic lung adenocarcinoma patients.Patients and Methods
We conducted a retrospective study to assess the effects of LCT on progression-free survival (PFS) and overall survival (OS). Patients with advanced-stage oligometastatic lung adenocarcinoma harboring sensitive mutation of epidermal growth factor receptor (EGFR) who received EGFR–tyrosine kinase inhibitor (TKI) or EGFR-TKI plus LCT were admitted to Shanghai Chest Hospital from January 2010 to December 2016. The PFS and OS of the 2 groups were accordingly analyzed.Results
A total of 231 patients (143 patients who received LCT plus EGFR-TKI [combination group] and 88 patients who only received EGFR-TKI only [monotherapy group]) were included in this study. Median PFS was significantly longer in the combination group (15 months; 95% confidence interval [CI], 13.611-16.389) than in the monotherapy group (10 months; 95% CI, 8.936-11.064; hazard ratio = 0.610; 95% CI, 0.461, 0.807; P = .000). The median OS in the combination group was 34 months (95% CI, 27.889, 40.111) versus 21 months (95% CI, 18.445, 23.555) in the monotherapy group (hazard ratio = 0.593; 95% CI, 0.430-0.817; P = .001).Conclusion
LCT combined with TKIs therapy was a feasible method that significantly improved PFS and OS among oligometastatic lung adenocarcinoma patients with EGFR mutations, and it thus might be considered as an important medical treatment during clinical management. 相似文献15.
Linda Agolli Stefano Bracci Luca Nicosia Maurizio Valeriani Vitaliana De Sanctis Mattia Falchetto Osti 《Clinical colorectal cancer》2017,16(1):58-64
Background
We evaluated a series of oligometastatic colorectal cancer (CRC) patients treated with stereotactic ablative body radiotherapy (SABR) delivered in all active lung metastases.Patients and Methods
Forty-four patients with 69 lung metastases were treated with SABR. Eleven patients presented with other sites of metastases before stereotactic body radiotherapy (SBRT), even though they had controlled/cured systemic disease.Results
The median follow-up was 36 months. The median overall survival (OS) was 38 months and 2 years, 3-year OS rates were 67.7% and 50.8%, respectively. The median progression-free survival (PFS) was 10 months and 2 years, 3-year PFS rates were 20.3% and 16.2%, respectively. Local recurrence occurred in 16 patients (36%).The first site of failure was local only in 22%, distant only in 35%, and local and distant in 14% of the patients. The 1-year, 2-year, and 3-year local PFS (LPFS) were 68.8%, 60.2%, and 54.2%, respectively. No Grade ≥ 3 toxicities were recorded in the univariate analysis; multiple lung metastases and synchronous oligometastatic disease were significantly associated with worse PFS (P = .04, and P < .001, respectively) and worse metastases-free survival (MFS; P = .04, and P < .001, respectively). The type of response was identified as a significant prognostic factor for OS (P = .014), PFS (P = .006), and LPFS (P < .001). In multivariate analysis single lung metastases treated with SBRT was associated with better MFS (P = .015). Metachronous oligometastatic disease and type of response were associated with significantly better PFS.Conclusion
Stereotactic body radiotherapy is a valid therapy in the treatment of lung metastases for oligometastatic CRC patients presenting long survival. The rate of local control remains lower compared with other primaries. Further prospective cohorts would better evaluate effective fractionation for patients with oligometastatic CRC. 相似文献16.
Elio Mazzone Felix Preisser Sebastiano Nazzani Zhe Tian Nicola Fossati Giorgio Gandaglia Andrea Gallina Denis Soulieres Derya Tilki Francesco Montorsi Shahrokh F. Shariat Fred Saad Alberto Briganti Pierre I. Karakiewicz 《Clinical genitourinary cancer》2019,17(2):105-113.e2
Background
Radical cystectomy (RC) may occasionally be performed in individuals with metastatic urothelial carcinoma of the bladder (mUCB). However, the role of lymph node dissection (LND) for such cases is unknown. Thus, we tested the effect of RC on cancer-specific mortality (CSM) and overall mortality in mUCB patients and the effect of LND and its extent on CSM.Patients and Methods
Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013), we identified patients with mUCB who underwent RC with or without LND or non-RC management. Kaplan-Meier analyses and multivariable Cox regression models (CRMs) were used, after propensity score matching. The number of removed nodes best predicting CSM was identified using cubic splines and then was tested in multivariable CRMs.Results
Of 2314 patients, 319 (13.8%) underwent RC. After 2:1 propensity score matching, CSM-free survival was 14 versus 8 months (P < .001), and overall mortality–free survival was 12 versus 7 months (P < .001) for, respectively, RC and non-RC patients. In multivariable CRMs, lower CSM (hazard ratio = 0.48; P < .001) and lower overall mortality (hazard ratio = 0.49; P < .001) rates were recorded in RC patients. LND status did not affect CSM-free survival (13 vs. 10 months; P = .1). Cubic splines-derived cutoff of ≥ 13 number of removed nodes showed better CSM-free survival (20 vs. 11 months; P = .02) and reduced CSM in CRMs (hazard ratio = 0.67; P = .02).Conclusion
Our study validates the survival benefit of RC in mUCB and highlights the importance of more extensive LND. These findings may corroborate the hypothesis of potential cytoreductive effect of surgery in the context of metastatic disease. 相似文献17.
Ting-Hui Wu Emily Han-Chung Hsiue Jih-Hsiang Lee Chia-Chi Lin Wei-Yu Liao Chao-Chi Ho Jin-Yuan Shih Chong-Jen Yu James Chih-Hsin Yang 《Clinical lung cancer》2018,19(3):e361-e372
Introduction
The association between the response to first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and survival in EGFR mutation-positive non–small-cell lung cancer (NSCLC) remains unclear. We studied the association between the response to first-line EGFR-TKIs and survival using Response Evaluation Criteria In Solid Tumors (RECIST) and maximal tumor shrinkage.Materials and Methods
We analyzed data from patients with advanced EGFR mutation-positive NSCLC enrolled in first-line gefitinib and afatinib trials. A total of 98 patients who achieved a response or stable disease and had ≥ 1 measurable target lesion were included. The association between the best response by RECIST or maximal tumor shrinkage and survival was analyzed in Kaplan-Meier and Cox regression models with the landmark method. The specified landmark time points were 8 weeks, the median time to maximal tumor shrinkage (16.5 weeks), and median progression-free survival (PFS; 56 weeks).Results
A total of 76 patients (77%) responded to gefitinib or afatinib. Of these 76 patients, 49 (64%) and 75 (99%) had achieved a response at 8 and 16.5 weeks, respectively. All responders had achieved a response by 56 weeks. The responders had a significantly longer PFS and overall survival (OS) compared with those with stable disease at 16.5 weeks (PFS, P = .003; OS, P < .001) and 56 weeks (PFS, P = .026; OS, P = .016) but not at 8 weeks (PFS, P = .104; OS, P = .313). Among the responders, greater tumor shrinkage was not associated with longer PFS or OS.Conclusion
Those with a response to first-line gefitinib or afatinib had more favorable PFS and OS compared with those with stable disease. A sufficient observation period was required for the response to occur and predict outcomes. Greater maximal tumor shrinkage in the responders was not predictive of survival. 相似文献18.
Jacqueline C. Barrientos Susan O’Brien Jennifer R. Brown Neil E. Kay Nishitha M. Reddy Steven Coutre Constantine Tam Stephen Mulligan Ulrich Jaeger Stephen Devereux Christopher Pocock Tadeusz Robak Stephen J. Schuster Anna Schuh Devinder Gill Adrian Bloor Claire Dearden Carol Moreno Peter Hillmen 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(12):803-813.e7
Background
Ibrutinib compared with ofatumumab significantly improves progression-free and overall survival in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).Patients and Methods
Measures of well-being were assessed in RESONATE, where previously treated patients with CLL/SLL were randomized to receive ibrutinib 420 mg/day (n = 195) or ofatumumab (n = 196) for up to 24 weeks. Endpoints included hematologic function, Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), disease-related symptoms, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (EORTC QLQ-C30), and medical resource utilization.Results
With up to 24 months’ follow-up (median, 16.4 months), 79% of cytopenic patients showed sustained hematologic improvement (82% with improved platelet count, 69% with improved hemoglobin) on ibrutinib versus 43% on ofatumumab (P < .0001). Higher rates of clinically meaningful improvement were demonstrated with ibrutinib versus ofatumumab for FACIT-F and EORTC global health. Greater improvement was observed in disease-related weight loss, fatigue, night sweats, and abdominal discomfort with ibrutinib versus ofatumumab. Hospitalizations in the first 30 days occurred less frequently with ibrutinib than ofatumumab (0.087 vs. 0.184 events/patient; P = .0198). New-onset diarrhea was infrequent with ibrutinib after the first 6 months (47% at ≤6 months vs. 5% at 12-18 months). With ibrutinib, grade ≥ 3 hypertension occurred in 6%, grade ≥ 3 atrial fibrillation in 4%, major hemorrhage in 2%, and tumor lysis syndrome in 1% of patients.Conclusion
Ibrutinib led to significant improvements in hematologic function and disease symptomatology versus ofatumumab, and can restore quality of life while prolonging survival in relapsed/refractory CLL/SLL. 相似文献19.
Fahrettin Covut Divya Gupta Raisa Pinto Nina Dambrosio Najla El Jurdi Howard Meyerson Masumi Ueda Merle Kolk Richard Creger Leland Metheny Brenda W. Cooper Paolo F. Caimi Ehsan Malek Folashade Otegbeye Hillard M. Lazarus Marcos De Lima Benjamin K. Tomlinson 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(2):73-82
Introduction
Induction chemotherapy with cytarabine and an anthracycline (7+3) remains the standard of care for acute myeloid leukemia (AML).Patients and Methods
We retrospectively analyzed 183 newly diagnosed AML patients to compare the utility of rapid peripheral blast clearance (PBC), day of peripheral blast disappearance, residual blasts, and cellularity at day 14 bone marrow biopsy (D14BM) in predicting clinical response to 7+3 induction, overall survival (OS), and relapse-free survival (RFS).Results
In multivariable logistic regression analysis, day 2 PBC > 85% [P = .0016] was the only predictor of remission status, with sensitivity and specificity of 75%. Peripheral blast disappearance within 5 days after induction and < 10% cellularity in D14BM predicted superior OS and RFS in multivariate analysis. Median follow-up of patients was 28 months since diagnosis. Two-year OS and RFS for patients with ≤ 10% versus > 10% cellularity at D14BM was 60.6% [95% confidence interval (CI), 50.8%-72.2%] versus 32.5% [95% CI, 23.0%-45.8%], and 51.9% [95% CI, 41.9%-64.3%] versus 28.8% [95% CI, 19.1%-43.4%], respectively [P = .0003 for OS and .002 for RFS].Conclusion
Rapid PBC after 7+3 induction showed a significant improvement in specificity compared with D14BM, with similar sensitivity. Neither of these methods were reliably specific tools for the decision of early reinduction, despite their prognostic value. Our findings indicate that morphological cellularity in D14BM is an independent prognostic factor for OS and RFS, regardless of blast percentage, and that ≤ 10% cellularity defines D14BM hypoplasia. 相似文献20.
Maxime Vanmechelen Diether Lambrechts Thomas Van Brussel Annelies Verbiest Gabrielle Couchy Patrick Schöffski Herlinde Dumez Philip R. Debruyne Evelyne Lerut Jean-Pascal Machiels Vincent Richard Maarten Albersen Vincent Verschaeve Stéphane Oudard Arnaud Méjean Pascal Wolter Jessica Zucman-Rossi Benoit Beuselinck 《Clinical genitourinary cancer》2019,17(2):e235-e246
