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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.
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3.
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4.
Baoan Hong Lin Cai Jiangyi Wang Shengjie Liu Jingcheng Zhou Kaifang Ma Jiufeng Zhang Bowen Zhou Xiang Peng Ning Zhang Kan Gong 《Clinical genitourinary cancer》2019,17(2):97-104.e1
Background
Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.Patients and Methods
Surgical specimens were recruited from 129 patients with sporadic ccRCC and 26 patients with VHL-associated hereditary ccRCC. The PD-L1 expression level was assessed using immunohistochemistry. Correlations between PD-L1 expression and clinicopathological features were analyzed.Results
In sporadic ccRCC, the positive expression rate of PD-L1 was 47.3% (61/129). Positive PD-L1 expression was correlated with advanced tumor T stage (P = .011), higher Fuhrman nuclear grade (P = .022), poor disease-free survival (P = .037), and sex (P = .025). In the VHL-associated hereditary ccRCC, positive PD-L1 expression rate was 34.6% (9/26), lower than that in sporadic ccRCC. Positive PD-L1 was correlated with higher Fuhrman nuclear grade (P = .008), but not with sex, age, tumor stage, or the onset age of VHL-associated tumors.Conclusion
Positive PD-L1 expression was correlated with the aggressive clinicopathological features in sporadic and VHL-associated hereditary ccRCC. Whether PD-L1 expression level in ccRCC is related to the effectiveness of programmed death-1/PD-L1 checkpoint inhibitor immunotherapy needs to be further investigated. 相似文献5.
Grace G. Wong Vincent Ha Michael P. Chu Deonne Dersch-Mills Sunita Ghosh Carole R. Chambers Michael B. Sawyer 《Clinical colorectal cancer》2019,18(1):72-79
Background
First-line adjuvant chemotherapy options for early-stage colorectal cancer (CRC) include CapeOx (capecitabine, intravenous oxaliplatin) and FOLFOX (intravenous 5-fluorouracil, leucovorin, oxaliplatin). Capecitabine is an oral prodrug analog of 5-fluorouracil, and recent studies have suggested that proton pump inhibitors (PPIs) may detrimentally affect capecitabine efficacy. Conversely, some literature suggests that PPIs may negatively affect CRC itself. To gain insight into the nature of PPIs’ effect on capecitabine and CRC, we investigated their effects on effectiveness of CapeOx versus FOLFOX chemotherapy.Patients and Methods
We conducted a retrospective chart review of 389 patients with stage II-III CRC who received adjuvant CapeOx or FOLFOX from 2004 to 2013. Information regarding PPI receipt, chemotherapy, and patient outcomes from medical records was analyzed.Results
Three-year recurrence-free survival was significantly lower in CapeOx-treated PPI recipients than non-PPI recipients (69.5 vs. 82.6%; P = .029). Unadjusted analysis showed that CapeOx-treated PPI recipients were twice as likely to experience cancer recurrence or death as CapeOx-treated non-PPI recipients (hazard ratio = 2.03; 95% confidence interval, 1.06-3.88; P = .033). FOLFOX-treated PPI recipients had a non–statistically significant difference in 3-year recurrence-free survival versus non-PPI recipients (82.9 vs. 61.7%; P = .066) and a non–statistically significant difference in recurrence/death (hazard ratio = 0.51; 95% confidence interval, 0.25-1.06; P = .071). No significant differences were seen in overall survival between groups.Conclusion
Our results suggest PPIs negatively affected recurrence-free survival in CapeOx-treated CRC patients and yielded no significant effects among FOLFOX-treated patients, potentially implicating a pharmacokinetic interaction between PPIs and capecitabine. No overall survival effects were seen. Given PPIs’ widespread use, further studies are required to corroborate our findings. 相似文献6.
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7.
Khurum Khan Jayant K. Rane David Cunningham Sheela Rao David Watkins Naureen Starling Eleftheria Kalaitzaki Martin Forster Chiara Braconi Nicola Valeri Marco Gerlinger Ian Chau 《Clinical colorectal cancer》2019,18(1):64-71.e1
Background
Gastrointestinal (GI) cancer patients may not be considered for therapy with fluoropyrimidines (FPs) because of previous cardiovascular (CV) toxicity or preexisting risk factors; such patients may benefit from raltitrexed-based therapy.Patients and Methods
Patient, tumor, and treatment characteristics, as well as clinical outcomes of all consecutively treated patients with raltitrexed at the Royal Marsden Hospital between October 1998 and July 2011 were examined. GI cancer patients who developed CV toxicity as a result of FPs and those with significant CV risk factors receiving raltitrexed were included in this analysis.Results
A total of 247 patients (155 and 92 with CV FP-related CV toxicities and significant CV risk factors, respectively) treated with raltitrexed alone or in combination were examined after a median follow-up of 47.1 months. CV toxicity profiles of patients receiving capecitabine (n = 110) and 5-fluorouracil (n = 45) were largely similar. Of raltitrexed-treated patients, 13 (5%) experienced CV toxicities and 1 (< 0.1%) died as a result of myocardial infarction. The median progression-free survival (PFS) and overall survival (OS) were 36.0 months (95% confidence interval [CI], 26.5-48.6) and 44.3 months (95% CI, 33.1-56.8), respectively. The 5-year survival for early stage GI malignancies (n = 140) was 62.0% (95% CI, 50.1-71.9). Median PFS and OS were not reached in this group (interquartile range = 38.4 months to NR); median PFS and OS for advanced GI malignancies (n = 107) were 18.8 (95% CI, 11.9-25.7) and 23.7 months (95% CI, 17.0-26.9), respectively.Conclusion
A raltitrexed-based regimen is well-tolerated therapy with comparable efficacy to FPs in patients with GI malignancies with significant CV toxicities or risk factors. 相似文献8.
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9.
Atsunari Kawashima Takayuki Kanazawa Kentaro Jingushi Taigo Kato Takeshi Ujike Akira Nagahara Kazutoshi Fujita Akiko Morimoto-Okazawa Kota Iwahori Motohide Uemura Ryoichi Imamura Hisashi Wada Norio Nonomura 《Clinical genitourinary cancer》2019,17(2):114-124
Background
There are no previous reports directly evaluating immunologic conditions in tumor microenvironment including both bladder cancer (BCa) and upper urinary tract carcinoma (UTUC). In this study, we aimed to clarify the difference of immunity status and its clinical significance depending on the tumor site in urothelial carcinoma.Patients and Methods
Tumor tissue–infiltrating lymphocytes were extracted from 70 urothelial cancer patients who underwent surgical resection (52 cases of BCa and 18 cases of UTUC). The immunologic classification was established by unsupervised clustering analysis according to the expression ratio of 9 extracellular surface markers measured by flow cytometry, and we examined the relationship between immunologic classification and clinical importance such as pathologic status and prognosis (progression-free survival and cancer-specific survival).Results
The immunologic condition was classified into 2 groups. Group 1 (n = 41) comprised the CD4 T-cell–dominant group and group 2 (n = 29) the immunologically activated group. This immunologic classification was significantly correlated with tumor grade (P = .020) but not tumor location in multivariate analysis. In invasive BCa patients (n = 33), progression-free survival and cancer-specific survival of group 2 were significantly worse than those of group 1 (P = .021 and P = .022, respectively), while there was no significant difference between groups 1 and 2 in patients with invasive UTUC (n = 17).Conclusion
Although there was no difference in the local immunologic condition of urothelial carcinoma between BCa and UTUC, its significance as a prognostic predictor might vary depending on tumor site. 相似文献10.
Omar Abdel-Rahman 《Clinical genitourinary cancer》2019,17(2):e329-e338
Background
The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.Patients and Methods
Within the PLCO (Prostate, Lung, Colorectal, and Ovary) trial, patients who were diagnosed with clinically localized prostate cancer and subsequently received treatment with prostatectomy or radiation therapy (with or without hormonal treatment) were included. Univariate and multivariate Cox regression analyses were then performed to determine factors affecting overall and prostate cancer-specific survival. Factors with P < .05 in univariate analysis were included in the multivariate analysis.Results
A total of 3953 patients were included in the current analysis. These included 2044 patients treated with prostatectomy and 1909 patients treated with radiation therapy with or without hormonal treatment. In an adjusted multivariate analysis for factors affecting overall survival, prostatectomy was associated with better overall survival compared with radiation therapy (hazard ratio, 0.548; 95% confidence interval [CI], 0.440- 681; P < .001). Likewise, in an adjusted multivariate analysis for factors affecting prostate cancer-specific survival, prostatectomy was associated with better prostate cancer-specific survival compared with radiation therapy (hazard ratio, 0.485; 95% CI, 0.286- 0.822; P = .007). Similar findings were found with propensity score matching and repeating the same analyses on the post-matching cohort.Conclusion
Prostatectomy seems to predict better overall and prostate cancer-specific survival compared with radiation therapy among patients with clinically localized prostate cancer diagnosed within the PLCO trial. 相似文献11.
Uday Yanamandra Prateek Deo Kamal Kant Sahu Ram Vasudevan Nampoothiri Nalini Gupta Anusree Prabhakaran Deb Prasad Dhibhar Alka Khadwal Gaurav Prakash Man Upadesh Singh Sachdeva Deepesh Lad Neelam Varma Subhash Varma Pankaj Malhotra 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):183-189.e1
Background
Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting.Patients and Methods
In this retrospective study, 415 consecutive patients with MM managed at a tertiary care center in North India during a study period of January 1, 2010 to December 31, 2015 were evaluated for MPE. The patients with MPE were analyzed for their clinical profile, diagnosis, treatment, and outcomes.Results
Of these 415 patients, 11 (2.65%) patients had MPE. The median age of the study population was 50 years with male preponderance. The majority of these patients had immunoglobin (Ig)G Kappa disease. All patients had higher than International Staging System stage I disease. MPE was a presenting feature at MM diagnosis in 45.45% (n = 5) of the patients, whereas the rest developed MPE during follow-up. MPE presented predominantly (81.8%) as a unilateral effusion. Concurrent extramedullary involvement at other site was seen in 45.45% (n = 5), with 3 (27%) patients having concurrent myelomatous ascites. Six of these were managed aggressively, whereas 5 patients opted for palliation. The outcomes were dismal (90.9% mortality), with a median survival of 2.47 months.Conclusion
MPE is a rare entity, and positive outcomes of therapy remain low with dismal prognosis. 相似文献12.
13.
I. Alex Bowman Alisha Bent Tri Le Alana Christie Zabi Wardak Yull Arriaga Kevin Courtney Hans Hammers Samuel Barnett Bruce Mickey Toral Patel Tony Whitworth Strahinja Stojadinovic Raquibul Hannan Lucien Nedzi Robert Timmerman James Brugarolas 《Clinical genitourinary cancer》2019,17(2):e263-e272
Background
Brain metastases (BM) occur frequently in patients with metastatic kidney cancer and are a significant source of morbidity and mortality. Although historically associated with a poor prognosis, survival outcomes for patients in the modern era are incompletely characterized. In particular, outcomes after adjusting for systemic therapy administration and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors are not well-known.Patients and Methods
A retrospective database of patients with metastatic renal cell carcinoma (RCC) treated at University of Texas Southwestern Medical Center between 2006 and 2015 was created. Data relevant to their diagnosis, treatment course, and outcomes were systematically collected. Survival was analyzed by the Kaplan-Meier method. Patients with BM were compared with patients without BM after adjusting for the timing of BM diagnosis, either prior to or during first-line systemic therapy. The impact of stratification according to IMDC risk group was assessed.Results
A total of 56 (28.4%) of 268 patients with metastatic RCC were diagnosed with BM prior to or during first-line systemic therapy. Median overall survival (OS) for systemic therapy-naive patients with BM compared with matched patients without BM was 19.5 versus 28.7 months (P = .0117). When analyzed according to IMDC risk group, the median OS for patients with BM was similar for favorable- and intermediate-risk patients (not reached vs. not reached; and 29.0 vs. 36.7 months; P = .5254), and inferior for poor-risk patients (3.5 vs. 9.4 months; P = .0462). For patients developing BM while on first-line systemic therapy, survival from the time of progression did not significantly differ by presence or absence of BM (11.8 vs. 17.8 months; P = .6658).Conclusions
Survival rates for patients with BM are significantly better than historical reports. After adjusting for systemic therapy, the survival rates of patients with BM in favorable- and intermediate-risk groups were remarkably better than expected and not statistically different from patients without BM, though this represents a single institution experience, and numbers are modest. 相似文献14.
Heather A. Jacene Trisha Youn Pamela J. DiPiro Jiani Hu Su-Chun Cheng Yoko Franchetti Hina Shah Jennifer R. Bellon Laura Warren Emily Schlosnagle Faina Nakhlis Jennifer Rosenbluth Eren Yeh Beth Overmoyer 《Clinical breast cancer》2019,19(2):146-155
Background
The aim of this study was to determine if, in inflammatory breast cancer (IBC), baseline metabolic activity (maximum standardized uptake value [SUVmax]) of primary tumor and involved regional lymph nodes (IRLN) are prognostic markers of response after neoadjuvant systemic therapy (NAS).Patients and Methods
Baseline 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography scans were retrospectively reviewed among 61 women with IBC who received NAS, had mastectomy, and had available pathology reports. Primary tumor and IRLN SUVmax were compared between patients with a pathologic complete response (pCR) versus those with residual disease after NAS. A multivariate Cox model was fit to evaluate the effects of SUVmax on overall survival, adjusting for pCR and stratified by receptor status and disease stage.Results
SUVmax in primary IBC tumors tended to increase with tumor grade (trend test P = .06) and was lower for stage III, non–triple-negative (TN) versus stage III, TN and stage IV, non-TN disease (P = .04). Neither primary tumor nor IRLN SUVmax was significantly different comparing pCR versus residual disease after NAS. Adjusting for pathology response in the overall survival model stratified by stage and receptor status, baseline SUVmax in primary IBC tumor was associated with an estimated hazard ratio of 1.10 (95% confidence interval, 0.97-1.25; P = .15) for patients with stage III, TN and stage IV, non-TN disease. This hazard ratio corresponded to a 1.74-fold risk of death with 1 standard deviation (SD = 5.9) increase in baseline SUVmax in primary IBC tumor.Conclusion
2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography provides prognostic information for newly diagnosed IBC. Larger studies are needed to confirm these findings and assess how such early information could affect treatment choices for IBC in the neoadjuvant setting. 相似文献15.
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
Background
There are no validated markers that predict response or resistance in patients with metastatic clear-cell renal cell carcinoma (mccRCC) treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors such as sunitinib and pazopanib. Recently, single nucleotide polymorphism (SNP) rs2981582 in Fibroblast Growth Factor Receptor 2 (FGFR2) was found to be associated with clinical outcome in patients with mccRCC treated with pazopanib and sunitinib. We aimed to validate these findings in patients treated with sunitinib.Materials and Methods
Germline DNA was collected in patients with mccRCC starting first-line systemic therapy with sunitinib. SNP rs2981582 in FGFR2 C>T was genotyped. Association of the genotype with response rate, tumor shrinkage, median progression-free survival (mPFS), and median overall survival (mOS) was studied.Results
We collected clinical data from 154 patients with available germline DNA. Baseline prognostic markers were well-balanced between both subgroups. Patients with the TT genotype had a poorer outcome compared with patients with the CT/CC genotype. The median shrinkage of selected tumor target lesions during treatment with sunitinib was ?16% versus ?31% (P = .002), mPFS was 8 versus 15 months (P = .0007), and mOS was 22 versus 33 months (P = .04), respectively. On multivariate analysis, rs2981582 remained an independent predictor of PFS (hazard ratio, 2.858; 95% confidence interval, 1.659-4.923; P < .0001) and OS (hazard ratio, 1.795; 95% confidence interval, 1.003-3.212; P = .049).Conclusion
Polymorphism rs2981582 in FGFR2 is correlated to PFS and OS in patients with mccRCC treated with sunitinib. Prospective validation of the impact of this SNP is warranted. 相似文献16.
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17.
V. Jenkins I. Solis-Trapala H. Payne M. Mason L. Fallowfield S. May L. Matthews S. Catt 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):99-107
Aims
Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment.Material and methods
Men with mCRPC from 20 UK cancer centres starting various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months.Results
In total, 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate [FACT-P] mean = –3.89, 95% confidence interval –6.7 to –1.05, P = 0.007; Trial Outcome Index [TOI] analysis mean = –3.10, 95% confidence interval –5.34 to –0.83, P = 0.007). Those who came off novel therapy and remained on luteinising hormone-releasing hormone agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale mean difference = –4.45, 95% confidence interval –7.06 to –1.83, P = 0.001; TOI mean difference = –5.62, 95% confidence interval –10.97 to –0.26, P = 0.040). At 3 and 6 months, men who reported pain at baseline improved (43%, 40%), but for others pain levels remained the same (45%, 42%) or worsened (13%, 18%). Information regarding supportive care was lacking throughout the period of time on the study.Conclusion
Most mCRPC treated patients experience reduced QoL and inadequate pain control. More help with pain management and better information provision regarding supportive care is warranted. 相似文献18.
Pashtoon Murtaza Kasi Faisal Shahjehan Jordan J. Cochuyt Zhuo Li Dorin Toma Colibaseanu Amit Merchea 《Clinical colorectal cancer》2019,18(1):e87-e95
Background
Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being diagnosed with rectal and colon cancers at our institutions.Patients and Methods
This study included 3381 rectal and colon cancer patients from the Mayo Clinic cancer registry from 1972 to 2017 who were diagnosed with rectal or colon cancer and who were < 50 years old. Patient and cancer characteristics are described. The Cochran-Armitage trend test was used to see if the change in percentage diagnosed at age < 50 years had a significant trend over the years. A linear regression model was fit to estimate the percentage change per year when the trend was approximately linear.Results
The percentage of patients diagnosed with rectal or colon cancer in different age categories over the years showed a rising trend for individuals aged < 50. Most of these tumors were distal (rectum, left-sided colon, and right-sided colon were 49.8%, 28.8%, and 21.4%, respectively). This was more so for patients < 50 diagnosed with rectal cancer, which showed a linear increase at a rate of 0.26% per year (P < .001).Conclusion
Our study affirms the rising proportion of colorectal cancers found in young individuals, with a linear ongoing rise of rectal cancers in particular. This may have implications for the current screening recommendations for colorectal cancers, which are already being revised. 相似文献19.
Yi-Long Wu Shun Lu Ying Cheng Caicun Zhou Jie Wang Tony Mok Li Zhang Hai-Yan Tu Lin Wu Jifeng Feng Yiping Zhang Alexander Valerievich Luft Jianying Zhou Zhiyong Ma You Lu Chengping Hu Yuankai Shi Christine Baudelet Jianhua Chang 《Journal of thoracic oncology》2019,14(5):867-875
Introduction
Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated NSCLC.Methods
CheckMate 078 was a randomized, open-label, phase III clinical trial in patients from China, Russia, and Singapore with squamous or nonsquamous NSCLC that had progressed during/after platinum-based doublet chemotherapy (ClinicalTrials.gov: NCT02613507). Patients with EGFR/ALK alterations were excluded. Patients (N = 504) were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks), stratified by performance status, tumor histology, and tumor programmed death ligand 1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate, progression-free survival, and safety.Results
OS was significantly improved with nivolumab (n = 338) versus docetaxel (n = 166); median OS (95% confidence interval): 12.0 (10.4–14.0) versus 9.6 (7.6–11.2) months, respectively; hazard ratio (97.7% confidence interval): 0.68 (0.52–0.90); p = 0.0006. Objective response rate was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5.3 months. Minimum follow-up was 8.8 months. The frequency of grade 3 or greater treatment-related adverse events was 10% with nivolumab and 48% with docetaxel.Conclusions
This is the first phase III study in a predominantly Chinese population reporting results with a programmed death 1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies. 相似文献20.
Joo Hwan Lee Mina Yu Sung Hwan Kim Jong Hoon Lee Soo-Yoon Sung Bae Kwon Jeong Songmi Jeong Taek Keun Nam Jae Uk Jeong Hong Seok Jang 《Clinical colorectal cancer》2019,18(1):e130-e139