Prognostic Factors For Long-term Outcome Research Articles

Ki67 as a prognostic factor for long-term outcome following surgery in gastrointestinal stromal tumors.

This study aimed to examine the value of Ki67 expression along with other potential prognostic factors for predicting overall survival and disease-free survival in patients with gastrointestinal stromal tumors who underwent curative resection. Sixty-eight histologically confirmed and operated patients with gastrointestinal stromal tumors were included. Clinical and follow-up data were retrieved from medical records and patients were contacted at the end of the study. The effects of certain clinical and histopathological parameters on survival outcomes were examined. Sixty-eight patients were followed for a mean duration of follow-up of 2923.3 patient-months. Twelve deaths (17.6%), seven metastasis (10.3%), and two local recurrences (2.9%) occurred. Overall survival was 102.5 months [95% confidence interval (CI), 88.3-116.8] and disease-free survival was 91.8 months (95% CI, 76.5-107.2). Multivariate analyses identified a high Ki67 index (≥ 10%) as an independent predictor of both poor overall survival (hazard ratio, 4.8; 95% CI 1.2-19.2; P=0.027) and poor disease-free survival (hazard ratio, 15.3; 95% CI, 4.7-50.2). A high Ki67 expression seems to be a useful prognostic factor that would aid in predicting disease course in gastrointestinal stromal tumors. These findings deserve further investigation in larger studies.

FOC5-3HISTOLOGICAL PARAMETERS DEFINE LONG-TERM PROGNOSIS IN ASYMPTOMATIC ALCOHOLIC LIVER DISEASE

Prognostic factors for long-term outcome in alcoholic liver disease (ALD) are not well defined. The aim of the present study was to investigate the prognostic impact of clinical, biochemical and histological parameters on liver-related long-term mortality of asymptomatic and symptomatic patients with biopsy-proven …

FOC5LIVER AND CARDIOVASCULARFOC5-1HISTOLOGICAL PARAMETERS DEFINE LONG-TERM PROGNOSIS IN ASYMPTOMATIC ALCOHOLIC LIVER DISEASE

Prognostic factors for long-term outcome in alcoholic liver disease (ALD) are not well defined. The aim of the present study was to investigate the prognostic impact of clinical, biochemical and histological parameters on liver-related long-term mortality of asymptomatic and symptomatic patients with biopsy-proven …

Prognosis of small cell lung cancer patients with diabetes treated with metformin.

It has been reported that metformin has an anticancer impact in various solid tumors, but its role in small cell lung cancer (SCLC) remains unclear. This study aimed to investigate the effect of metformin on survival in diabetic SCLC patients. A total of 79 SCLC patients with diabetes treated in our hospital between 2000 and 2010 were enrolled. The clinicopathological data and survival time were collected and evaluated. Univariate and multivariate analyses were used to investigate the association between metformin use and the survival of SCLC. Among the 79 diabetic patients, 36 patients took metformin. The median OS and DFS were significantly better in the metformin group compared to non-metformin group (OS 18.0 vs 11.5 months, p < 0.001; DFS 10.8 vs 6.5 months, p < 0.001). Multivariate Cox analysis indicated that metformin use was an independent prognostic factor for long-term outcome (HR = 0.549, 95 % CI 0.198-0.978, p = 0.001). The prognosis of SCLC patients with diabetes treated with metformin was improved, which might be considered a potential useful anticancer drug in treating SCLC patients.

Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy.

Background:Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time.Methods:Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length.Results:The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The ‘prognostic benefit' of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1–0.4) at 6 months to 2.2 (95% CI 1.3–3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1–2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4–1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group.Conclusion:From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.

Low and High Radio-Iodine-131 Doses in Postoperative Ablation in Differentiated Thyroid Carcinoma

The goals of post-surgical RAI therapy in patients with differentiated DTC are to ablate residual normal thyroid tissue that may facilitate surveillance,) Also the potential tumoricidal effect on residual microscopic RAI-avid disease, and to provide a posttreatment whole-body scan that may reveal undetected local or distant metastases.Although, these goals are important, the ultimate endpoint of postsurgical ablation is to minimize DTC recurrence and death by eliminating residual normal thyroid tissue or residual microscopic disease that could be a focus for future recurrence(1). Successful RAI-131 thyroid remnant ablation is associated with better prognosis with regard to both recurrence-free and overall survival, lower rates of distant metastases, and reduced cancer mortality rates, compared with only surgery or surgery and L-thyroxin therapy alone (2). It also facilitates long-term follow up of patients with DTC. It was shown byVerburg et al. that a successful ablation itself seems to be a highly important prognostic factor for long-term outcome. They found that the patients with a successful ablation, 87% were still free of the disease after 10 years, whereas of the patients with an unsuccessful ablation, only 50% were free of disease with thyroid cancer-related survival was (93% versus 78%) (P > 0.001)(3). After four decades of follow-up, based on regression modeling of 1510 patients without distant metastases at the time of initial therapy,Mazzaferri and Kloos found thyroid remnant ablation to be an independent variable that reduced loco regional recurrence, distant metastases, and cancer death. A similar observation has also been made by the National Thyroid Cancer Treatment Cooperative Study group (4), they had reconfirmed that postoperative RAI treatment was associated with improved cancer-specific mortality rates and reduced disease progression in both papillary and follicular cancer(5).

Long-Term Outcome of Patients with Myelodysplastic Syndromes (MDS) Treated with Hypomethylating Agents (HMA): A Report on Behalf of the MDS Clinical Research Consortium

Background:Therapy with HMA is now the standard of care for pts with MDS and chronic myelomonocytic leukemia (CMML) with complete response (CR) rates of 7% to 35%, median response durations of 9 to 10 months, and median survival of 20 to 24 months. While allogeneic stem cell transplantation (ASCT) is curative in pts with MDS, the long-term outcome of pts treated with HMA remains unknown.Aims:The aims of the study are to assess the long-term outcome of pts with MDS treated with HMA and to identify prognostic factors of long-term outcome. This may help selecting patients for this long-term treatment in whom ASCT may not be indicated.Methods:We reviewed the records of 511 pts with diagnosed MDS (n=409) and CMML (n=102) treated from 4/2000 to 4/2014 and who were treated with HMA. Pts who received ASCT (n=65) were excluded. Thus, a total of 446 pts were evaluable for the study. The probabilities of leukemia-free survival (LFS) and overall survival (OS) were estimated using the method of Kaplan and Meier. Univariate and multivariate analyses were performed to identify potential factors associated with the achievement of response with logistic regression models and survival with Cox proportional hazard regression models.Results:The median follow-up for the entire cohort was 13.6 months. Pt characteristics are outcomes described in Table 1. Best responses to HMA were CR in 124 (28%) pts, CRp in 27 (6%), PR in 9 (2%), HI in 31 (7%). Median duration of response was 7 months (1-68). 130 (29%) transformed into AML after a median of 11 months (11-60). At the last follow-up 133 (30%) remained alive. The median LFS and OS were 16.1 and 16.2 months respectively. The 2- and 5-year LFS and OS rates were 29% and 11% and 34% and 12%, respectively. By multivariate analysis, baseline characteristics associated with OS included WBC (>4 vs. ≤4), ferritin (>500 vs. ≤500), hemoglobin (>10 vs. ≤10), platelets (>500 vs. ≤500) and cytogenetics (high vs. intermediate vs. low risk) (p<0.05). Since the relative impact of each of these 5 factors on survival was similar, we assigned an arbitrary value of 1 to each of them, except for cytogenetics (0=low risk; 1=intermediate risk; and 2=high risk). Patients with 0-2 (n=265) or 3-5 (n=180) adverse factors had a median survival of 18 and 14 months, respectively (p= 0.001). To assess the benefit of achieving a response, we repeated the multivariate survival analysis using an 8-week landmark that excluded 38 patients who died within 8 weeks. The median survival was 15 months overall (8 and 20 months for patients with and without CR/CRp, PR/HI, respectively; p<0.001). The multivariate analysis included 315 patients and selected the achievement of response (CR/CRp/PR/HI vs. others), WBC (>4 vs. ≤4), ferritin (>500 vs. ≤500), platelets (>500 vs. ≤500) and cytogenetics (0=low risk; 1=intermediate risk; and 2=high risk) as independently associated with survival improvement Patients with 0-2 (n=244) or 3-5 (n=162) adverse factors had a median survival of 19 and 13 months, respectively (p<0.001).Conclusion:Our current analyses identified a small subset of pts with MDS in whom outcome of therapy with HMA is excellent and can be differentially predicted.Table 1Patient Characteristics and OutcomesParameter (N=446)Number (%); Median [range]Age (years)70 (13-92)White Blood Cell Count (x 109/L)3.5 (0.5-212)Ferritin465.0 (0-10971)Hemoglobin (g/dL)9.7 (6-16)Platelets (x 109/L)68.0 (4-987)Bone marrow blasts (%)6.0 (0-19)Prior malignancy198 (44)Prior chemotherapy133 (30)Prior radiotherapy85 (19)Prior Transfusion134 (30)Cytogenetics (by IPSS)Low213 (48)Intermediate78 (17.5)High144 (8)Missing11 (2.5)WHORA47 (10.5)RARS16 (4)RCMD75 (17)RAEB204 (46)MDS-U8 (2)CMML95 (21)Missing1 (0.2)IPSSLow46 (10)Intermediate-1193 (43)Intermediate-2156 (35)High36 (8)Missing15 (3)MDA ScoreLow59 (13)Intermediate-1113 (25)Intermediate-2124 (28)High113 (25)Missing37 (8)Type of HMAAzacitidine/ AZA+189 (42)Decitabine/DAC257 (58)Response to HMACR124 ( 28)CRp27 (6)PR9 (2)HI31 (7)NR121 (27)Died on therapy23 (5)NE6 (1.4)Missing105 (23.5)Median duration of response (mos)7.2 (1-68)Transformed into AML130 (29)Dead313 (70) DisclosuresNo relevant conflicts of interest to declare.

Donor-recipient matching in lung transplantation: which variables are important?†.

Donor to recipient (D/R) matching in lung transplantation (LTx) is usually directed by blood group (identity or compatibility) and predicted total lung capacity (pTLC) based on height and age. Other donor (D) and recipient (R) characteristics such as cytomegalovirus (CMV) serology (±), gender [male (M)/ female (F)] and age are often ignored, but the impact of D/R mismatch for these variables and their combinations on outcome is less investigated. The early and late outcomes in 461 lung recipients (149 single-lung and 312 double-lung) transplanted between July 1991 and December 2009 were explored, comparing different D/R combinations for gender (M/F), age (<20/21 to 45/≥ 45 years), CMV (±), blood group (identical/compatible) and pTLC (-9%Δ, +11%Δ). Overall 5-, 10-, 15- and 20-year survival rates were 69, 50, 37 and 37%, respectively, and were significantly better in females {HR [95% confidence interval (CI)]: 0.5 (0.3-0.9); P = 0.023} and worse in older recipients [HR (95% CI): 1.6 (1.2-2.2); P = 0.003]. On univariate analysis, survival was significantly worse in recipients with gender opposite to that of the donor (39% for mismatch vs 51% for match at 10 years; P = 0.04), but not for other D/R matching variables: age (P = 0.89), pTLC (P = 0.14), CMV (P = 0.15), blood group (P = 0.82) and their combinations. The best survival at 5 years was seen in female donor (DF)/female recipient (RF) (80%), the worst in DF/male recipient (RM) (47%), and intermediate in male donor (DM)/RF (72%) and DM/RM (63%); P = 0.0001. On multivariate analysis, D/R gender mismatch was found to be the sole negative predictive factor for survival with an 80% increased risk of mortality [HR (95% CI): 1.8 (1.1-2.8); P = 0.01]. In our patient cohort, survival after LTx was superior in female and younger recipients. D/R gender mismatch may be an important prognostic factor for long-term outcome. A gender combination of DF/RM should be avoided. The exact reasons for these differences remain speculative.

Prognostic factors of long-term outcome in cases of severe traumatic brain injury

IntroductionThe purpose of this monocentric study was to assess the long-term outcome of a group of severe traumatic brain-injured patients and explore the prognostic values of some clinical and paraclinical parameters available at the initial stage. MethodologyThe patients included were victims of severe traumatic brain injuries in 2007 or 2008. A standardized assessment was performed for each patient including clinical, radiological, and electrophysiological data collected at the initial stage, The outcomes were assessed at least 2 years after injury. Depending on the patients’ availability and ability to communicate, the assessments included measures of dependency for activities of daily living (ADL), cognitive functions, behaviour, mood, and quality of life. ResultsEighteen patients were included, of whom ten were autonomous for ADL at the time of assessment. Memory complaints, attentional deficits, anxiety, and irritability were the main long-term impairments observed. A correlation analysis showed significant correlations between the dependency level (as rated by the Functional Independence Measure) and each of length of coma, length of the post-traumatic amnesia, and the N100 auditory evoked potentials. DiscussionThese results confirm the uniqueness of each patient regarding the long-term consequences of a traumatic brain injury and the multi-determined nature of each prognosis.

Cognitive outcomes in childhood with craniopharyngioma

It has been proposed that hypothalamic involvement is an important prognostic factor for long-term outcomes in children with craniopharyngioma. In this issue of The Journal, Özyurt et al, investigate the hypothesis that impaired executive and memory performance is associated with hypothalamic involvement in children with craniopharyngioma. The authors compared cognitive performance in 15 children with craniopharyngioma and hypothalamic involvement and 24 age- and intelligence-matched control subjects. The results showed that, as predicted, compared with healthy controls, the children with hypothalamic involvement had significantly lower scores with regards to memory and executive functioning. Patients with a high-grade relative to a low grade of hypothalamic involvement showed worse cognitive outcomes. The authors, therefore, recommend regular neuropsychological testing during follow-up of such patients and individually tailored cognitive rehabilitation. Article page 876▶ Neuropsychological Outcome in Patients with Childhood Craniopharyngioma and Hypothalamic InvolvementThe Journal of PediatricsVol. 164Issue 4PreviewTo test memory performance and executive functions in patients with childhood craniopharyngioma and hypothalamic involvement. Full-Text PDF

A new encephalitis with GABAA receptor antibodies

In the past decade, several autoimmune neurological syndromes have been identified. Many of these syndromes, especially those responsive to immunotherapy, involve antibodies to cell-surface antigens, such as the NMDA receptor, LGI1, and the GABAB receptor. 1 Bien CG Vincent A Barnett MH et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012; 135: 1622-1638 Crossref PubMed Scopus (416) Google Scholar , 2 Davis R Dalmau J Autoimmunity, seizures, and status epilepticus. Epilepsia. 2013; 54: 46-49 Crossref PubMed Scopus (63) Google Scholar Detailed investigations have led to the recognition of distinct features that aid in early diagnosis. For example, faciobrachial dystonic seizures—very brief (<3 seconds) contractions of the arm and usually the ipsilateral face—are highly suggestive of the non-paraneoplastic, autoimmune syndrome associated with anti-voltage-gated potassium channel complex antibodies, specifically the anti-LGI1 variant. 3 Irani SR Michell AW Lang B et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol. 2011; 69: 892-900 Crossref PubMed Scopus (613) Google Scholar This is a treatable disorder with an excellent prognosis when recognised early. The faciobrachial dystonic seizures usually precede the rest of the syndrome, which consists of hyponatraemia and limbic encephalitis. Treatment with immunotherapy, especially corticosteroids, in the early phase can not only lead to improvement but can prevent the limbic encephalitis. 4 Irani SR Stagg CJ Schott JM et al. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain. 2013; 136: 3151-3162 Crossref PubMed Scopus (292) Google Scholar Similarly, the clinical features of anti-NMDA receptor encephalitis are quite distinct, with psychiatric presentation, followed by rapid deterioration, including central apnoea requiring ventilatory support, and prominent dyskinesias, often in young women, and often in those with ovarian teratomas. 5 Titulaer MJ McCracken L Gabilondo I et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013; 12: 157-165 Summary Full Text Full Text PDF PubMed Scopus (1857) Google Scholar Extreme delta brushes on EEG might also be suggestive of this syndrome. 6 Schmitt SE Pargeon K Frechette ES Hirsch LJ Dalmau J Friedman D Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012; 79: 1094-1100 Crossref PubMed Scopus (482) Google Scholar Identification of the antibodies to cell-surface antigens in these syndromes not only suggests good response to immunotherapy but also raises suspicion of specific yet-to-be-detected underlying malignancies—eg, small-cell lung cancer is present in half of patients with limbic encephalitis with GABAB (metabotropic) receptor antibodies. 7 Höftberger R Titulaer MJ Sabater L et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology. 2013; 81: 1500-1506 Crossref PubMed Scopus (313) Google Scholar Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodiesHigh titres of serum and CSF GABAA receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABAA receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable. Full-Text PDF

Original Article: Prognostic Factors of Long-Term Outcome and Functional Status Following Spontaneous Cerebellar Hemorrhage

Cerebellar hemorrhage (CH) has a higher early mortality rate compared with other types of intracranial hemorrhage and the survivors often suffer from momentous disability. Hence, the prognostic factors of long-term outcome beyond 6 months after CH are clinically valuable, however only three studies were reported in the literature. Sixty-one patients with CH were retrospectively analyzed at least 6 months after hemorrhage. The long-term outcome of all patients and long-term functional status of survivors beyond 6 months (the patients who died within 6 months after hemorrhage were excluded) were assessed using the modified Rankin Scale (mRS): favorable outcome (mRS 0 - 2) and unfavorable outcome (mRS 3 - 6). All of the prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression models. There were 16 (26.2%) patients in the favorable outcome group and 45 (73.8%) in the unfavorable outcome group with respect of long-term outcome in all patients. The radiological brainstem compression (HR = 3; p = 0.015) was shown to be an independent predictor. On the other hand, 46 out of 61 (75.4%) patients survived beyond 6 months. In total, 16 (34.7%) patients had a favorable functional status, and 65.3% (30/46) had a persistent unfavorable functional status. Moreover, only age 365 years (HR = 3; p = 0.019) was an independent predictor. Radiological brainstem compression and age 365 were respectively shown to be a strong prognostic factor for long-term outcome and functional status among survivors beyond 6 months after hemorrhage in patients with CH.

Oncologic impact of anastomotic leakage in rectal cancer surgery according to the use of fibrin glue: case-control study using propensity score matching method

BackgroundThe oncologic impact of anastomotic leakage after rectal cancer surgery remains controversial. MethodsBetween January 1999 and December 2010, 1,148 patients with rectal cancer who underwent curative surgery with sphincter preservation were retrospectively reviewed. Using the propensity score matching method, 328 patients with fibrin glue were matched to 328 patients without fibrin glue, and oncologic outcomes were compared in the matched groups. ResultsAnastomotic leakage was diagnosed in 76 patients (6.6%). On multivariate analysis, fibrin glue was the independent predictor of prevention of anastomotic leakage. In the 656 matched groups, patients with anastomotic leakage had significantly worse 5-year local recurrence-free survival and disease-free survival than those without leakage. Multivariate analysis confirmed that anastomotic leakage was an independent prognostic factor of both local recurrence and disease-free survival, but the use of fibrin glue was not associated with the long-term outcomes when controlling for confounders. ConclusionsAnastomotic leakage is a major independent prognostic factor for long-term outcomes. Fibrin glue has a protective effect of anastomosis, without oncologic advantages.

Surgical treatment for bronhial carcinoid tumors prognostic factors for long-term outcome

Methods Surgically resected specimen (men n = 59; women n = 72, age 48 ± 15) from 111 TC (84.7%) and 20 AtC (15.3%) patients were studied. The histological type, T-status, N-status (TC 94 N0, 17 N1/2; AtC 16 N0, 4 N1), pTNM stage (TC-I n = 81, II n = 17, III+IV = 13; AtC-I n = 12, II-IV n = 8), surgery (55 simple lobectomies, 16 bilobectomies, 24 pneumonectomies (4 extended), 15 segmentectomies, 16 sleeve lobectomy (in 2 of them combined with sleeve resection of pulmonary artery), 5 sleeve resection of main bronchus), and immunohistochemical expression (on 64 TCs and 13 AtCs) of p-HspB5, Hsp27 and mTOR were evaluated. Kaplan-Meier, Wilcoxon, Cox regression analyses were the statistical methods used.

Successful conservative treatment of patients with MRI-verified meniscal lesions

To follow a prospective cohort of consecutive patients with MRI-verified meniscal lesions to identify pre-treatment prognostic factors for long-term results following arthroscopic or conservative treatment. In the course of 1 year, 291 patients with knee pain and clinically suspected of meniscal lesion were referred to the regional orthopaedic division and subjected to MRI and clinical examination by an experienced surgeon. Patients with MRI-verified meniscal lesions were treated according to an arthroscopy restrictive strategy meaning that treatment was initiated by conservative treatment. Arthroscopy was only performed if satisfying pain relief was not obtained. The Lysholm score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were obtained at baseline and after 12-24 months. A multiple linear regression model was used to investigate which pre-treatment prognostic factors were associated with improvement in the KOOS subscale pain from baseline to follow-up. An MRI-verified meniscal lesion was found in 185 patients (64%). Among these, 58% were treated successfully by conservative treatment. A high KOOS subscale pain score at baseline was associated with less improvement from baseline to follow-up. Bucket-handle lesions were associated with larger improvement from baseline to follow-up compared to flap-tear lesions. MRI findings and clinical status measured by KOOS subscale pain are prognostic for improvement among patients treated for MRI-verified meniscal lesions. Good results were observed for both operative and conservative treatment. The success rate for conservative treatment was 58%. Prospective cohort study, Level II.

The Presence of Mutations in Epidermal Growth Factor Receptor Gene Is Not a Prognostic Factor for Long-Term Outcome after Surgical Resection of Non–Small-Cell Lung Cancer

The presence of mutation in EGFR gene is known as a predictive marker for the response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. However, whether or not these EGFR mutations are prognostic factors for non-small-cell lung cancer (NSCLC) is debatable. We retrospectively collected a series of samples from patients whose EGFR mutation status had been tested, and analyzed their survival. The pathologic cell types of 863 patients (520 men, 343 women) were squamous cell carcinoma in 227, adenocarcinoma in 636 patients. EGFR mutations were detected in 354 patients and it was frequently observed in adenocarcinoma in younger, early-stage, female never-smokers. In univariate analysis of younger, early-stage, never-smoker women, bronchioloalveolar carcinoma pattern and the presence of EGFR mutation showed better long-term survival. However, in multivariate analysis, age, pathologic stage, and smoking status remained significant prognostic factors, whereas EGFR mutation was not. For recurrence, pathologic stage was the only independent prognostic factor. After recurrence, smoking status was the only significant risk factor that affected postrecurrence survival. However, when EGFR TKIs were used in EGFR-mutated patients, survival was longer than for those treated with conventional chemotherapy. Although the EGFR mutation is a predictive marker for EGFR TKI response, it is not a prognostic factor in NSCLC. The clinical observation that patients with EGFR mutation seem to survive longer may be because EGFR mutation is more frequently associated with other good prognostic factors. Once there is a recurrence, administration of EGFR TKI for patients with EGFR mutation may increase survival.

Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study

Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined. We aimed to assess the presentation of the disease, the spectrum of symptoms, immunotherapies used, timing of improvement, and long-term outcome. In this multi-institutional observational study, we tested for the presence of NMDAR antibodies in serum or CSF samples of patients with encephalitis between Jan 1, 2007, and Jan 1, 2012. All patients who tested positive for NMDAR antibodies were included in the study; patients were assessed at symptom onset and at months 4, 8, 12, 18, and 24, by use of the modified Rankin scale (mRS). Treatment included first-line immunotherapy (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy (rituximab, cyclophosphamide), and tumour removal. Predictors of outcome were determined at the Universities of Pennsylvania (PA, USA) and Barcelona (Spain) by use of a generalised linear mixed model with binary distribution. We enrolled 577 patients (median age 21 years, range 8 months to 85 years), 211 of whom were children (<18 years). Treatment effects and outcome were assessable in 501 (median follow-up 24 months, range 4-186): 472 (94%) underwent first-line immunotherapy or tumour removal, resulting in improvement within 4 weeks in 251 (53%). Of 221 patients who did not improve with first-line treatment, 125 (57%) received second-line immunotherapy that resulted in a better outcome (mRS 0-2) than those who did not (odds ratio [OR] 2·69, CI 1·24-5·80; p=0·012). During the first 24 months, 394 of 501 patients achieved a good outcome (mRS 0-2; median 6 months, IQR 2-12) and 30 died. At 24 months' follow-up, 203 (81%) of 252 patients had good outcome. Outcomes continued to improve for up to 18 months after symptom onset. Predictors of good outcome were early treatment (0·62, 0·50-0·76; p<0·0001) and no admission to an intensive care unit (0·12, 0·06-0·22; p<0·0001). 45 patients had one or multiple relapses (representing a 12% risk within 2 years); 46 (67%) of 69 relapses were less severe than initial episodes (p<0·0001). In 177 children, predictors of good outcome and the magnitude of effect of second-line immunotherapy were similar to those of the entire cohort. Most patients with anti-NMDAR encephalitis respond to immunotherapy. Second-line immunotherapy is usually effective when first-line treatments fail. In this cohort, the recovery of some patients took up to 18 months. The Dutch Cancer Society, the National Institutes of Health, the McKnight Neuroscience of Brain Disorders award, The Fondo de Investigaciones Sanitarias, and Fundació la Marató de TV3.

Prognostic significance of expression of cyclooxygenase‐2, vascular endothelial growth factor, and epidermal growth factor receptor in nasopharyngeal carcinoma

The association between expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and the long-term outcomes in treated nasopharyngeal carcinoma (NPC) was studied. Expression of COX-2, VEGF, and EGFR by immunohistochemical (IHC) staining was assessed in 128 patients with NPC. Overall survival (OS), disease-free survival (DFS), locoregional control, and distant metastasis-free survival rates were compared for different expression levels of each marker. Multivariate analysis was by the Cox regression model. Median follow-up after radiation therapy ± chemotherapy was 116 months. Univariate and multivariate analyses demonstrated that COX-2, VEGF, EGFR, and clinical stage were all independent predictors for OS, DFS, locoregional control, and distant metastasis-free survival rates. High expression of COX-2, VEGF, and EGFR were independent adverse prognostic factors for long-term outcomes in nonmetastatic NPC independent of clinical stage.

Analysis of prognostic factors in 333 Chinese patients with high‐grade osteosarcoma treated by multidisciplinary combined therapy

To investigate prognostic factors for long-term outcomes in Chinese patients with high-grade osteosarcoma of the extremities or trunk treated by multidisciplinary combined therapy. In total, 333 consecutive patients with non-metastatic or primary metastatic high-grade osteosarcoma of the extremities or trunk were retrospectively reviewed to analyze the correlation between survival and sex, age, site, histological type, clinical stage, alkaline phosphatase (ALP) level, preoperative chemotherapy or not, response to preoperative chemotherapy, postoperative chemotherapy cycles and manner of surgery. The combined therapy included preoperative and postoperative chemotherapy as well as limb salvage surgery or amputation. The median survival time was 52 months for all 333 patients. Univariate analysis revealed that sex, ALP level, preoperative chemotherapy and cycle numbers of postoperative chemotherapy may influence the prognosis of high-grade osteosarcoma of the extremities or trunk. Multivariate analysis revealed that the female, a normal ALP level, preoperative chemotherapy with good response and ≥4 cycles of postoperative chemotherapy correlated with a better outcome. Preoperative chemotherapy is important in high-grade osteosarcoma treatment and a good response to it is an important marker of prognosis. It should be given with ≥ cycles of postoperative chemotherapy after surgery.

Neutrophil gelatinase‐associated lipocalin as an early biomarker of acute kidney injury in liver transplantation

Acute kidney injury (AKI) is a common complication and a significant prognostic factor of long-term outcome in patients undergoing liver transplantation. We evaluated the utility of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) concentrations as biomarkers of AKI during and after liver transplantation. We prospectively enrolled 19 adult patients who underwent living-related liver transplantation (LRLT). Serial blood and urine samples were collected at baseline and at 2, 4, 10, 16, 24, 30, 40, and 48 h after reperfusion, and their concentrations of NGAL were measured, with urinary NGAL corrected by urinary creatinine concentration to compensate for urine output. AKI was defined by Risk-Injury-Failure-Loss-End-stage kidney disease (RIFLE) criteria as a ≥50% increase in serum creatinine from baseline. Eleven of 19 patients were diagnosed with AKI according to RIFLE criteria. Urinary NGAL/urine creatinine ratio increased immediately after reperfusion and peaked four h later and preceded a ≥50% elevation in serum Cr by 19.0 h (p = 0.001). Plasma NGAL also tended to be elevated 13.0 h earlier than serum creatinine (p = 0.075). The urinary NGAL/urine creatinine ratio may be an early biomarker of AKI in adult patients undergoing LRLT.