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1.
Moller AK Loft A Berthelsen AK Damgaard Pedersen K Graff J Christensen CB Perell K Petersen BL Daugaard G 《The oncologist》2011,16(4):445-451
Background.
Carcinoma of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies for which no primary tumor site can be identified after extensive diagnostic workup. Failure to identify the primary site may negatively influence patient management. The aim of this review was to evaluate 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as a diagnostic tool in patients with extracervical CUP.Materials and Methods.
A comprehensive literature search was performed and four publications were identified (involving 152 patients) evaluating 18F-FDG PET/CT in CUP patients with extracervical metastases. All studies were retrospective and heterogeneous in inclusion criteria, study design, and diagnostic workup prior to 18F-FDG PET/CT.Results.
18F-FDG PET/CT detected the primary tumor in 39.5% of patients with extracervical CUP. The lung was the most commonly detected primary tumor site (∼50%). The pooled estimates of sensitivity, specificity, and accuracy of 18F-FDG PET/CT in the detection of the primary tumor site were 87%, 88%, and 87.5%, respectively.Conclusions.
The present review of currently available data indicates that 18F-FDG PET/CT might contribute to the identification of the primary tumor site in extracervical CUP. However, prospective studies with more uniform inclusion criteria are required to evaluate the exact value of this diagnostic tool. 相似文献2.
Zoran Gatalica Sherri Z. Millis Semir Vranic Ryan Bender Gargi D. Basu Andreas Voss Daniel D. Von Hoff 《Oncotarget》2014,5(23):12440-12447
Background
Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Despite extensive laboratory and imaging efforts, the primary site usually cannot be unequivocally confirmed, and the treatment for the most part remains empirical. Recently, identification of common cancer pathway alterations in diverse cancer lineages has offered an opportunity to provide targeted therapies for patients with CUP, irrespective of the primary site.Patients and Methods
1806 cancers of unknown primary were identified among more than 63,000 cases profiled at Caris Life Sciences. Multiplatform profiling of the tumor samples included immunohistochemistry, gene sequencing and in situ hybridization methods in an effort to identify changes in biomarkers that are predictive of drug responses.Results
Biomarkers associated with a potential drug benefit were identified in 96% of cases. Biomarkers identified included those associated with potential benefit in nearly all classes of approved cancer drugs (cytotoxic, hormonal, targeted biological drugs). Additionally, biomarkers associated with a potential lack of benefit were identified in numerous cases, which could further refine the management of patients with CUP.Conclusion
Comprehensive biomarker profiling of CUP may provide additional choices in treatment of patients with these difficult to treat malignancies. 相似文献3.
Martin Schuler Jürgen R. Fischer Christian Grohé Sylvia Gütz Michael Thomas Martin Kimmich Claus‐Peter Schneider Eckart Laack Angela Märten for the Afatinib Compassionate Use Consortium 《The oncologist》2014,19(10):1100-1109
Background.
Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients receiving afatinib within a compassionate-use program (CUP).Patients and Methods.
Patients with advanced NSCLC progressing after one line or more of chemotherapy and one line or more of EGFR-TKI treatment with either an EGFR mutation or documented clinical benefit were enrolled. Data collection was not monitored or verified by central review. The intention of this CUP was to provide controlled preregistration access to afatinib for patients with life-threatening diseases and no other treatment option.Results.
From May 2010 to October 2013, 573 patients (65% female; median age: 64 years [range: 28–89 years]) were enrolled, with strong participation of community oncologists. Comorbidities were allowed, including second malignancies in 11% of patients. EGFR mutation status was available in 391 patients (72%), and 83% tested mutation positive. Median time to treatment failure (TTF) of 541 patients treated with afatinib was 3.7 months (range: 0.0 to >29.0 months). Median TTF was 4.0 and 2.7 months in patients with adenocarcinomas and squamous cell carcinomas, respectively, and 4.6 months in patients with EGFR-mutated NSCLC. Adverse events were generally manageable.Conclusion.
Afatinib was able to be given in a real-world setting to heavily pretreated patients with EGFR-mutated or EGFR-TKI-sensitive NSCLC. Acknowledging the constraints of data collection in a CUP, afatinib appears to be safe and to confer some clinical benefit in this population. 相似文献4.
Meiri E Mueller WC Rosenwald S Zepeniuk M Klinke E Edmonston TB Werner M Lass U Barshack I Feinmesser M Huszar M Fogt F Ashkenazi K Sanden M Goren E Dromi N Zion O Burnstein I Chajut A Spector Y Aharonov R 《The oncologist》2012,17(6):801-812
Background.
Cancers of unknown primary origin (CUP) constitute 3%–5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%–15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. Cancers of unknown/uncertain primary origins present major diagnostic and clinical challenges because the tumor tissue of origin is crucial for selecting optimal treatment. MicroRNAs are a family of noncoding, regulatory RNA genes involved in carcinogenesis. MicroRNAs that are highly stable in clinical samples and tissue specific serve as ideal biomarkers for cancer diagnosis. Our first-generation assay identified the tumor of origin based on 48 microRNAs measured on a quantitative real-time polymerase chain reaction platform and differentiated 25 tumor types.Methods.
We present here the development and validation of a second-generation assay that identifies 42 tumor types using a custom microarray. A combination of a binary decision-tree and a k-nearest-neighbor classifier was developed to identify the tumor of origin based on the expression of 64 microRNAs.Results.
Overall assay sensitivity (positive agreement), measured blindly on a validation set of 509 independent samples, was 85%. The sensitivity reached 90% for cases in which the assay reported a single answer (>80% of cases). A clinical validation study on 52 true CUP patients showed 88% concordance with the clinicopathological evaluation of the patients.Conclusion.
The abilities of the assay to identify 42 tumor types with high accuracy and to maintain the same performance in samples from patients clinically diagnosed with CUP promise improved utility in the diagnosis of cancers of unknown/uncertain primary origins. 相似文献5.
Joshua A. Roth Paul Billings Scott D. Ramsey Robert Dumanois Josh J. Carlson 《The oncologist》2014,19(5):466-476
Purpose.
Life Technologies has developed a 14-gene molecular assay that provides information about the risk of death in early stage non-squamous non-small cell lung cancer patients after surgery. The assay can be used to identify patients at highest risk of mortality, informing subsequent treatments. The objective of this study was to evaluate the cost-effectiveness of this novel assay.Patients and Methods.
We developed a Markov model to estimate life expectancy, quality-adjusted life years (QALYs), and costs for testing versus standard care. Risk-group classification was based on assay-validation studies, and chemotherapy uptake was based on pre- and post-testing recommendations from a study of 58 physicians. We evaluated three chemotherapy-benefit scenarios: moderately predictive (base case), nonpredictive (i.e., the same benefit for each risk group), and strongly predictive. We calculated the incremental cost-effectiveness ratio (ICER) and performed one-way and probabilistic sensitivity analyses.Results.
In the base case, testing and standard-care strategies resulted in 6.81 and 6.66 life years, 3.76 and 3.68 QALYs, and $122,400 and $118,800 in costs, respectively. The ICER was $23,200 per QALY (stage I: $29,200 per QALY; stage II: $12,200 per QALY). The ICER ranged from “dominant” to $92,100 per QALY in the strongly predictive and nonpredictive scenarios. The model was most sensitive to the proportion of high-risk patients receiving chemotherapy and the high-risk hazard ratio. The 14-gene risk score assay strategy was cost-effective in 68% of simulations.Conclusion.
Our results suggest that the 14-gene risk score assay may be a cost-effective alternative to standard guideline-based adjuvant chemotherapy decision making in early stage non-small cell lung cancer. 相似文献6.
7.
Afatinib in Non‐Small Cell Lung Cancer Harboring Uncommon EGFR Mutations Pretreated With Reversible EGFR Inhibitors
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David F. Heigener Christian Schumann Martin Sebastian Parvis Sadjadian Ingo Stehle Angela M?rten Anne Lüers Frank Griesinger Matthias Scheffler for the Afatinib Compassionate Use Consortium 《The oncologist》2015,20(10):1167-1174
Background.
Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-naïve (TKI-naïve) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown.Materials and Methods.
In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in patients harboring uncommon EGFR mutations were reported.Results.
In 60 patients (63% female, median age 63 years [range: 30–84 years]), a total of 66 uncommon EGFR mutations including 30 T790M mutations were reported (18.4% and 11%, respectively, of known EGFR mutations within the CUP). Most patients (67%) received afatinib as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in patients with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in patients with common mutations (n = 165). Pronounced activity was observed with E709X mutations (TTF >12 months). No new safety signals were detected.Conclusion.
Afatinib is clinically active and well tolerated in many TKI-pretreated NSCLC patients harboring uncommon EGFR mutations. Compared with results reported in TKI-naïve patients, activity was also indicated in patients with T790M and exon 20 insertion mutations.Implications for Practice:
This analysis consists of a large database of non-small cell lung cancer patients with uncommon EGFR mutations who were previously treated with reversible EGFR tyrosine kinase inhibitors. Although indirectly assessed, the results indicate that patients with uncommon EGFR mutations can derive benefit from treatment with the irreversible ErbB family blocker afatinib, even in some cases of tumors harboring resistance-mediating exon 20 mutations. In this study, adverse events were modest and consistent with previous reports on afatinib. 相似文献8.
Norma A. Palma Siraj M. Ali Jamie O'Connor Deepa Dutta Kai Wang Salil Soman Gary A. Palmer Deborah Morosini Jeffrey S. Ross Doron Lipson Phil J. Stephens Mayur Patel Vincent A. Miller Nicholas Koutrelakos 《Case reports in oncology》2014,7(2):503-508
Background
Carcinoma of unknown primary (CUP) accounts for 3–5% of all adult solid tumors. An extensive search for the anatomic site of origin is often undertaken in an attempt to tailor systemic treatment, but the latter often has limited efficacy – especially in the setting of an initial treatment failure. Molecularly targeted therapy is an emerging approach that may offer greater efficacy and less toxicity but is most likely to be effective when pairing a tumor harboring a sensitizing genomic alteration with an agent directed at the altered gene product. We report a patient with a CUP harboring a MET amplification with a complete metabolic response to crizotinib despite also harboring a KRAS mutation.Methods
Ge-nomic profiling was performed using a clinical next-generation-sequencing-based assay, FoundationOne®, in a CAP-accredited laboratory certified by Clinical Laboratory Improvement Amendments (Foundation Medicine, Cambridge, Mass., USA).Results
The CUP harbored both MET amplification (16 copies) and a KRAS G12V mutation. The patient was treated with crizotinib, a MET inhibitor, and has experienced a complete normalization of tumor metabolic activity for more than 19 months. Conclusions: Genomic profiling of CUP may reveal clinically meaningful genomic alterations that can guide targeted therapy decision-making. The use of this approach should be studied prospectively as a strategy for the effective treatment of CUP patients and for avoiding resource-intensive workups to identify the tumor site of origin.Key words: Carcinoma of unknown primary, MET amplification, KRAS mutation, Crizotinib, Next-generation sequencing 相似文献9.
Objective: To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 89 patients with stage ⅢB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results: A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. Conclusions: The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable. 相似文献
10.
Background:
Cancer of unknown primary (CUP) is the fourth most common cause of cancer death. With advanced diagnostics and treatments, we investigated the proportion of cancers diagnosed as CUP, treatment outcomes and association with socioeconomic disparities.Methods:
We analysed trends in CUP diagnosis and outcome within the Surveillance, Epidemiology, and End Results registry between 1973 and 2008.Results:
The percentage of all cancers diagnosed as CUP has decreased over time comprising <2% of cancers since 2007. A higher proportion of CUP was diagnosed in the elderly, females, blacks and residents of less affluent or less educated counties. Median survival of all CUP patients was 3 months, with no improvement over time. The 5-year survival significantly improved in those with squamous histology (squamous cell carcinoma; SCC) but only marginally in non-SCC. Factors associated with a longer survival on multivariate analysis included white race; female; <65 years old; most recent decade at diagnosis; SCC; married; a histological diagnosis; and treatment with radiotherapy (all P<0.001). Despite the improvement in survival with radiotherapy, its use was less frequent in females and blacks.Conclusion:
The percentage of cancers diagnosed as CUP is decreasing but prognosis remains poor, particularly in non-SCC CUP. However, significant socioeconomic disparities exist in diagnosis and survival, suggesting inequalities in access to diagnostic investigations and treatment. 相似文献11.
Marleen J. ter Avest Romane M. Schook Lyan G. Koudstaal Katrien Grünberg Marinus A. Paul Egbert F. Smit Pieter E. Postmus 《Case reports in oncology》2014,7(1):122-125
Background
The finding of a renal mass on imaging is suggestive of metastatic non-small cell lung cancer in the presence of a lung tumor but can also have another origin.Case Report
We describe the case of a patient diagnosed with stage IV lung cancer based on a renal metastasis. A second opinion including review of histopathological data and additional imaging followed by lung surgery and cryoablation of the kidney lesion revealed two tumors of different origins, non-small cell lung cancer and a renal cell carcinoma.Discussion
The presence of a renal mass diagnosed on a CT scan in a patient with lung cancer is not always synonymous with metastatic disease. Confirmation of diagnosis by tissue sampling is mandatory, especially if a synchronous primary tumor is possible.Key words: Non-small cell lung cancer, Second opinion, Renal cell carcinoma, Diagnosis/treatment, Metastatic disease, Synchronous primary tumor 相似文献12.
Hidetaka Uramoto Hirohiko Akiyama Yuki Nakajima Hiroyasu Kinoshita Takuya Inoue Futoshi Kurimoto Yu Nishimura Yoshihiro Saito Hiroshi Sakai Kunihiko Kobayashi 《Case reports in oncology》2014,7(3):700-710
Background
Although the concept of induction therapy followed by surgical resection for locally advanced non-small cell lung cancer (LA-NSCLC) has found general acceptance, the appropriate indications and the strategy for this treatment are still controversial.Methods
From 2000 through 2008, 36 patients received concurrent chemoradiotherapy followed by surgery. We retrospectively reviewed these cases, analyzed the outcomes and examined the prognosis.Results
The median radiation dose given was 60 Gy. Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered to 9 cases, and a carboplatin-based chemotherapy regimen was administered to 27. A complete resection was performed in 94% of the patients. Seventeen (47.2%) patients exhibited a complete pathological response, and downstaging was induced in 26 (72%) cases. The morbidity and 30-day mortality rates were 11.1 and 0%, respectively. The 5-year overall survival rate in the patients with complete resection (n = 33) was 83.3%.Conclusions
Induction chemoradiotherapy followed by surgery for LA-NSCLC provided a favorable prognosis for selected patients. A complete pathological response was found in about half of cases. This strategy is feasible and was associated with low morbidity and high resectability rates, suggesting that it contributed to improving the treatment results.Key words: Non-small cell lung cancer, Locally advanced non-small cell lung cancer, Induction chemotherapy, Surgical resection, Prognosis 相似文献13.
Cost‐Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early‐Stage Non‐Small Cell Lung Cancer
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David D. Stenehjem Kraig M. Yager Joshua Jones Rajesh Kaldate Uwe Siebert Diana I. Brixner 《The oncologist》2016,21(2):196-204
Background.
A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC.Materials and Methods.
Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty.Results.
Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY.Conclusion.
The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds.Implications for Practice:
Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and costs in patients with low-risk disease. This study used an economic model to assess the effectiveness and costs associated with using a prognostic test to guide adjuvant chemotherapy decisions compared with the current standard of care in patients with non-small cell lung cancer. When compared with current standard care, the prognostic test was potentially cost effective at commonly accepted thresholds in the U.S. This study can be used to help inform decision makers who are considering using prognostic tests. 相似文献14.
C Kahlert M Pecqueux N Halama H Dienemann T Muley J Pfannschmidt F Lasitschka F Klupp T Schmidt N Rahbari C Reissfelder C Kunz A Benner C Falk J Weitz M Koch 《British journal of cancer》2014,110(2):441-449
Background:
Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets.Methods:
Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay.Results:
We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases.Conclusion:
Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer. 相似文献15.
Xue-Ning Yang Ze-Rui Zhao Wen-Zhao Zhong Qiang Nie Ri-Qiang Liao Song Dong 《中国癌症研究》2015,27(6):538-544
Background
We want to establish a lobe-specific mediastinal lymphadenectomy protocol for solitary pulmonary nodules (SPNs) in non-small cell lung cancer (NSCLC).Methods
We retrospectively analyzed 401 patients with pathological diagnoses of NSCLC who underwent lobectomy, bilobectomy, or pneumonectomy with systematic lymphadenectomy from March 2004 to June 2011 in our hospital. All of the patients enrolled had a SPN preoperatively. Information about the primary tumor location, lymph node metastasis, and other baseline data were collected. Stepwise logistic regression was used to identify the key factors indicating non-regional mediastinal lymph node metastases (NRM).Results
Of the primary tumors, 117, 39, 74, 104, and 67 were in the right upper lung (RUL), right middle lung (RML), right lower lung (RLL), left upper lung (LUL), and left lower lung (LLL), respectively. Stepwise regression showed that #2,4, #10,11, and #10,11 as well as #7 was the key lymph node station for RUL, LUL, and lower lobes: #2,4 [odds ratio (OR)=28.000, 95% confidence interval (CI): 2.917-268.790, P=0.004] for RUL, #10,11 (OR=31.667, 95% CI: 2.502-400.833, P=0.008) for LUL, #10,11 (OR=19.540, 95% CI: 4.217-90.541, P<0.001) and #7 (OR=7.395, 95% CI: 1.586-34.484, P=0.011) for lower lobes, respectively. Patients with tumors >2 cm rarely had NRM without primary regional mediastinal involvement.Conclusions
With rigid consideration, a lobe-specific lymphadenectomy is feasible in practice. This protocol can be used when the lobe-specific key nodes are negative in intraoperative frozen sections, especially for NSCLC diagnosed as SPN <2 cm preoperatively. 相似文献16.
Z Mohamed D J Pinato F A Mauri K-W Chen P M-H Chang R Sharma 《British journal of cancer》2014,110(1):208-213
Background:
Carcinoma of unknown primary (CUP) is a clinical presentation with a poor prognosis. Inflammation-based prognostic systems are stage-independent prognostic predictors in various malignancies. We aimed to assess the accuracy of the modified Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as objective prognostic models in CUP.Methods:
We derived inflammatory scores in 60 consecutive CUP referrals to the Imperial College oncology unit between 1996 and 2011. Patient demographics, treatment and staging data and full blood profiles were collected. An independent cohort of 179 patients presenting to the Taipei Veterens Hospital between 2000 and 2009 were used as a ‘validation'' data set. Uni- and multivariate survival analysis was used to predict the overall survival (OS).Results:
Sixty patients were included: median age 61 (range: 33–86); 51% men; median OS 5.9 months (0.7–42.9); 88% with distant metastases. On univariate analysis NLR >5 (P=0.04) and mGPS (score 1–2) (P=0.03) correlated with OS. Multivariate analysis demonstrated significant hazard ratios for NLR; 2.02 (CI 1.0–4.1) (P=0.04) and mGPS; 1.52 (CI 1.0–2.3) (P=0.03). These findings were reinforced by analysis of the validation data.Conclusion:
NLR and mGPS are independent, externally validated prognostic markers in CUP, with superior objectivity compared with performance status. 相似文献17.
Nutritional Status,Body Surface,and Low Lean Body Mass/Body Mass Index Are Related to Dose Reduction and Severe Gastrointestinal Toxicity Induced by Afatinib in Patients With Non‐Small Cell Lung Cancer
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Oscar Arrieta Martha De la Torre‐Vallejo Diego López‐Macías David Orta Jenny Turcott Eleazar‐Omar Macedo‐Pérez Karla Sánchez‐Lara Laura‐Alejandra Ramírez‐Tirado Vickie E. Baracos 《The oncologist》2015,20(8):967-974
Background.
The main reason for dose reduction of afatinib is gastrointestinal toxicity (GT). In a phase II study, we analyzed anthropometrical, nutritional, and biochemical factors associated with GT induced by afatinib.Materials and Methods.
Patients diagnosed with non-small cell lung cancer who progressed to prior chemotherapy received 40 mg of afatinib. Malnutrition was determined by Subjective Global Assessment, and lean body mass (LBM) was determined by computed tomography scan analysis using a pre-established Hounsfield unit threshold. Toxicity was obtained during four cycles by Common Terminology Criteria for Adverse Events.Results.
Eighty-four patients were enrolled. Afatinib was administered as the second, third, and fourth line of treatment in 54.8%, 38.1%, and 7.12% of patients, respectively. Severe diarrhea, mucositis, and overall severe GT were present in 38.9%, 28.8%, and 57.5%, respectively. Of the patients, 50% developed dose-limiting toxicity (DLT). Patients with malnutrition have higher risk for severe GT. Patients with lower LBM and body mass index developed more DLT (71.4% vs. 18.8%).Conclusion.
Malnutrition is associated with a higher risk of severe GT induced by afatinib. Determination of nutritional status and body composition are helpful in identifying patients at higher risk of severe GT and could allow initiating treatment with lower doses according to tolerance.Implications for Practice:
Body composition analysis, specifically lean body mass quantification, and nutritional status assessment are significant clinical variables to take into account when assessing oncological patients. This study on patients with non-small cell lung cancer treated with afatinib showed the important impact that malnutrition and low lean body mass have on the risk for developing dose-limiting toxicity and severe gastrointestinal toxicity. Still more research needs to be done to explore dose adjustment according to lean body mass, especially in drugs that are given at fixed doses, such as afatinib. However, this study presents evidence for the clinical oncologist to have a closer follow-up with malnourished patients and even to consider a lower starting dose until therapeutic dose is achieved. 相似文献18.
Angelina Cistaro Natale Quartuccio Alireza Mojtahedi Piercarlo Fania Pier Luigi Filosso Alfredo Campenni Umberto Ficola Sergio Baldari 《Radiology and oncology》2013,47(3):219-223
Background
The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up.Patients and methods.
Forty-nine patients with stage I–II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography (18F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated.Results
There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9.Conclusions
In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence. 相似文献19.
Myung‐Ju Ahn Sang‐We Kim Byoung‐Chul Cho Jin Seok Ahn Dae Ho Lee Jong‐Mu Sun Dan Massey Miyoung Kim Yang Shi Keunchil Park 《The oncologist》2014,19(7):702-703
Background.
This phase II single-arm trial evaluated afatinib, an irreversible inhibitor of the ErbB receptor family as third-line treatment of Korean patients with advanced non-small cell lung cancer (NSCLC) and tumors with wild-type EGFR. Currently, no standard therapy exists for these patients.Methods.
Eligible patients had stage IIIB/IV wild-type EGFR lung adenocarcinoma and had failed to benefit from two previous lines of chemotherapy but had not received anti-EGFR treatment. Patients received oral afatinib at 40 mg per day until disease progression or occurrence of intolerable adverse events (AEs). The primary endpoint was confirmed objective tumor response (OR) rate (confirmed complete response [CR] or partial response [PR]). Secondary endpoints included disease control rate (DCR; OR or stable disease for ≥6 weeks), progression-free survival (PFS), and safety.Results.
Forty-two patients received afatinib treatment, and 38 of those were included in efficacy analyses. No confirmed CRs or PRs were reported. DCR was 24% (9 of 38 patients), with a median disease control duration of 19.3 weeks. Median PFS was 4.1 weeks (95% confidence interval: 3.9–8.0). Frequently reported AEs (mainly grades 1 and 2) were rash/acne (88%), diarrhea (62%), and stomatitis (57%).Conclusion.
Heavily pretreated patients with wild-type EGFR NSCLC treated with afatinib monotherapy did not experience an objective response and only 24% had disease stabilization lasting more than 6 weeks. AEs were manageable and consistent with the expected safety profile. 相似文献20.
Zhong‐Zhe Lin Wen‐Yi Shau Yu‐Yun Shao Yen‐Yun Yang Raymond Nien‐Chen Kuo James Chih‐Hsin Yang Mei‐Shu Lai 《The oncologist》2012,17(10):1294-1302