Prognostic Significance of Absolute Lymphocyte Count,Absolute Monocyte Count,and Absolute Lymphocyte Count to Absolute Monocyte Count Ratio in Follicular Non-Hodgkin Lymphoma

IntroductionRecently, the lymphocyte to monocyte ratio (LMR) has been proposed as an easily determinable prognostic factor in patients with cancer, including lymphomas. The objective of this study was the evaluation of the impact of baseline absolute lymphocyte count (ALC), absolute monocyte count (AMC), and the LMR on the treatment response and prognosis in follicular lymphoma (FL).Patients and MethodsThe data of 100 patients with a FL variant, admitted and treated between January 2009 and June 2018, were analyzed.ResultsThe area under the receiver operator characteristic curve and cutoff values of ALC, AMC, and LMR for discrimination between survival times using receiver operating characteristic curves showed 0.57 × 10⁹/L as the most discriminative ALC cutoff value, 1.235 ×10⁹/L as the most discriminative AMC cutoff value, and 1.63 as the most discriminative LMR cutoff value. Progressive disease and stable disease after first-line therapy and mortality rate were significantly associated with lower ALC, higher AMC, and higher LMR. Shorter overall survival (OS) was significantly associated with patients with lower ALC when compared with those having higher ALC. Shorter OS and progression-free survival (PFS) were significantly associated with higher AMC when compared with those having lower AMC. Shorter OS and PFS were significantly associated with lower LMR when compared with those having higher LMR. High-risk Follicular Lymphoma International Prognostic Index as well as low LMR were considered as risk factors for prediction of OS in all the studied patients with FL in univariate analysis and multivariate analysis.ConclusionALC, AMC, and LMR at diagnosis are simple indices, which reflect the host systemic immunity and can predict the clinical outcomes in FL.     

Study of Pemetrexed-based Chemotherapy for Patients with Locally Advanced or Metastatic Cancers

Purpose: This study was conducted to observe the efficacy and safety of pemetrexed based chemotherapyin treating patients with locally advanced or metastatic cancers as first-line, second-line or third-line therapy.Materials and Methods: From May 2011 to January 2015, we recruited 29 patients with advanced breast cancer,19 patients with advanced ovary cancer, 17 patients with advanced esophageal cancer,5 patients with advancedgallbladder cancer,5 patients with advanced cervical cancer and 1 patient with advanced tongue cancer inJiangsu Cancer Hospital and Research Institute.All of them were pathologically confirmed and treated withpemetrexed based chemotherapy. After two cycles of treatment,efficacy and safety can be evaluated. Results:For pemetrexed based regimens,including 76 patients with 6 kinds of advanced cancer were considered eligiblefor inclusion. Complete remission represents CR, partial remission represents PR, stable disease represents SD,progressive disease represents PD. Among 29 patients with advanced breast cancer, 4 patients chose pemetrexedbased regimens as second-line treatment,1 of them was PR,the other 3 got SD. The last 25 patients made useof this chemotherapy as third-line treatment, except one patient could not be assessed, 2 of them got PR,6 ofthem got SD,the remaining 16 of them finally were PD.19 patients with advanced ovary cancer,5 patients usedthis regimens as second-line treatment, 3 of them got PD,the remaining patients got SD, respectively. The last14 patients made use of pemetrexed based regimens as third-line treatment,. RR (CR+PR) was 28.5%. Among17 patients with advanced esophageal cancer, 2 patients made use of pemetrexed based regimens as first-linetreatment,both of them got PR.4 of them used this chemotherapy as second-line regimen, except 2 patients couldnot be assessed,the remaining 2 was PD at last. The last 11 patients was third-line users, RR (CR+PR) was 18.2%.Among 5 patients with advanced gallbladder cancer, pemetrexed based regimens was used in 1 patient as firstlinetreatment and 1 patient as second-line treatment. The curative effect was SD and PD, respectively. 3 patientsaccepted pemetrexed based regimens as third-line treatment, 2 of them got PD as results and another was SD.Among 5 patients with advanced cervical cancer, just 1 patient adopted pemetrexed based regimens as first-linetreatment, whose curative effect was PR.2 patients chose this chemotherapy regimens as second-line treatment.Both of them got PD as their consequence. The last 2 patients made use of the regimens as third-line treatment,the effect of them was PD and SD, respectively. The one who with advanced tongue cancer, pemetrexed basedregimens was used as second-line treatment, and the consequence was PD. About 71.1% patients experienced bonemarrow suppression. Among them, 5 patients reached 4 grade. Other toxicity of pemetrexed were neurotoxicity,fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment.Conclusions: Pemetrexed based chemotherapy has considerable effect in patients with advanced cancers suchas breast cancer,esophageal cancer and ovary cancer. More randomly clinical trials are needed to verify theresults.     

The Blood Neutrophil-to-lymphocyte Ratio Predicts Survival in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib

Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poorsurvival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate theprognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC whoreceived sorafenib monotherapy. Methods: A total of sixty-five patients with advanced HCC, not eligible forlocoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender,tumoral characteristics, performance status and NLR were analyzed. Results: Median OS and TTP for the entirecohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLRat baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months)compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (≤4) (P=0.01). Age ≤65, NLR>4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariateanalysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors ofpoorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months)compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). Conclusions: Highbaseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.     

Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors andthe extent these markers improve prognostic classification for patients with inoperable advanced or metastaticgastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemicinflammatory factors such as circulating white blood cell count and its components as well as that combined toform inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio(NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariateand multivariate analyses were performed to examine the impact of inflammatory markers on overall survival(OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count,a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well aselevated NLR/PLR , GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstratedthat only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independentpredictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and highGPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated withfirst-line chemotherapy. Upon validation of these data in independent studies, stratification of patients usingthese markers in future clinical trials is recommended.     

局部进展期食管鳞癌全身化疗联合瘤体注射治疗临床研究

[目的]探讨提高食管鳞癌化疗的局部病灶反应率的方法。[方法]使用顺铂(DDP)+氟尿嘧啶(5-Fu)全身化疗联合内镜下瘤体注射丝裂霉素C+5-Fu治疗非广泛期非手术适应证食管鳞癌。全身化疗DDP20mg/m2,静滴,d1～4,5-Fu300mg/(m2·d),静滴,d1～5。5-Fu同步应用叶酸片20mg/次,3次/d,21d一个周期,两周期评价疗效。常规胃镜操作,镜下在肿瘤四周及顶部3～5注射点瘤体注射药物:5-Fu250mg、丝裂霉素(MMC)2mg。每周一次,两周休一周,一个疗程3～5次。[结果]全组共计69例可评价病例共完成132个周期。CR20例(28.98%)、PR34例(49.27%)、SD15例(21.73%),总获益率100%,总反应率(CR+PR)78.26%(54/69)。55例患者治疗结束不久进食困难症状得到改善。中位疾病进展时间10.0个月,1年生存率84.09%(37/44)。瘤体注射术后无食管穿孔发生,食管疼痛者6例,病灶渗血7例,对症处理后可缓解。药物相关不良反应发生状况总体轻微。主要副反应包括恶心呕吐Ⅰ度55.07%(38/69),Ⅱ度33.33%(23/69)。白细胞下降发生率34.78%(24/69),Ⅲ～Ⅳ度下降为10.14%(7/69)。[结论]全身化疗联合瘤体注射是一种单纯利用化疗方法来提高食管鳞癌局控率的良好途径。     

局部晚期宫颈鳞癌流式细胞术分析与放射治疗预后的关系

 目的 研究局部晚期宫颈鳞癌流式细胞术分析结果（DNA倍体、SPF和PI）与放疗预后的关系，探讨它们在预测宫颈癌放疗效果中的价值。方法 68例ⅢB期宫颈鳞癌病人在放疗前钳取宫颈癌组织，制备成单细胞悬液，采用流式细胞术检测癌细胞DNA倍体、S期比例（SPF）及增殖指数（PI），分析他们及其他临床参数与患者根治性放疗后疾病复发和生存的关系。结果 在68例标本中，异倍体检出率为47．1％（32／68），SPF和PI值为分别为（7．49±2．91）和（12．89±3．75）；在随访期间，全组宫颈癌患者复发率为44．1％（30／68）；二倍体组和异倍体组的5年无复发生存率分别为52．7％和35．2％（P〈0．（15），高SPF组和低SPF组5年无复发生存率分别为25．3％和56．6％（P〈0．05），高PI组和低PI组5年无复发生存率分别为37．5％和49．3％（P〈0．05）；经多因素分析显示，肿瘤大小和SPF是影响宫颈癌患者无复发生存的独立预后因素。结论 通过流式细胞术检测宫颈癌组织SPF可以预测局部晚期宫颈鳞癌放射治疗后的预后。     

肝癌患者外周血AFP mRNA检测的临床追踪观察

采用逆转录及巢式聚合酶链式反应（ＲＴＰＣＲ）和Ｓｏｕｔｈｅｒｎ杂交方法对肝癌患者的早期血行微转移灶进行检测并做临床随访观察。１０例原发性肝癌患者（ＨＣＣ），经手术切除的癌组织，检测ＡＦＰｍＲＮＡ均为阳性。３９例ＨＣＣ患者中有２４例外周血检测为阳性，阳性率６１．５％。１ａ时间随访到２８例患者，９例阴性结果的病人，１例死亡，死亡率为１１．０％。３例临床证实有转移灶。１９例阳性结果的病人，９例死亡，死亡率为４７．３％，４例临床证实有转移灶。ＲＴＰＣＲ结果不同的两组经卡方检验，Ｐ＜０．０１，患者预后也有明显的差异。检测ＨＣＣ患者外周血中癌细胞是阳性结果，可以说明癌细胞已进入血循环。随访结果显示ＨＣＣ患者外周血中ＡＦＰｍＲＮＡ检测呈阳性则同患者出现血行微转移灶及预后有一定的相关性，可以给临床提供一个肿瘤有远处转移的参考指标。     

肝癌患者外周血中白蛋白mRNA检测及其临床意义

目的 以白蛋白（Ａｌｂ）ｍＲＮＡ作为肝细胞在外周血中的标志物,从而早期出血中的微量肝癌细胞。方法 用ＲＴＰＣＲ方法检测２０例正常人,１０例急、慢性肝炎,１０例肝硬化患者及３９例原发性肝癌（ＨＣＣ）患者外周血中的白蛋白ｍＲＮＡ。结果 ３９例原发性肝癌（ＨＣＣ）患者中有１２例呈阳性,其中８例经临床证实为有转移的患者中,６例Ａｌｂ ｍＲＮＡ为阳性,阳性率为７５．０％,其它３１例临床上没有明显转移的患者中     

晚期胃癌患者外周血CEA mRNA的表达及临床意义

目的 探讨晚期胃癌患者外周血中CEA mRNA的表达及其临床意义.方法 将临床确诊的32例晚期胃癌根据影像学检查分为血行转移组13例,局部浸润组19例,对照组为胃良性病变10例.以外周血为检测标本,用反转录巢式聚合酶链反应技术(RT-NP-PCR)检测CEA mRNA.结果 初诊时对照组阳件率0%,局部浸润组阳性率63.16%,血行转移组阳性率92.31%,两胃癌组与对照组比较差异有统计学意义(P<0.01),两胃癌组比较差异无统计学意义(P>0.05);6个月后无血行转移病例阳性率50.00%,有血行转移病例阳性率90.00%,两者比较差异有统计学意义(P<0.05).结论 应用RT-NP-PCR技术检测晚期胃癌患者外周血CEA mRNA可作为晚期胃癌血源性播散的指标,对指导选择治疗方案和判断预后有重要意义.     

Skeletal Muscle Mass Reduction Velocity as a Simple Prognostic Indicator for Patients with Metastatic Urothelial Carcinoma Receiving Second-Line Chemotherapy

Background: Patients with metastatic urothelial carcinoma (mUC) have an uncertain prognosis. The aim of the current study was to evaluate the prognostic potential of a skeletal muscle mass reduction index measured by computed tomography (CT) for mUC patients undergoing second-line gemcitabine and docetaxel (GD) chemotherapy. Methods: We retrospectively reviewed 44 patients with mUC who received second-line GD chemotherapy between 2006 and 2015 in our hospital. Skeletal muscle area (SMA) at the third lumbar vertebra was measured using CT images obtained from medical records, and a skeletal muscle index (SMI) was calculated for each patient as: SMI = SMA / height2. Changes in SMI across timepoints (SMI inclination) were calculated as: SMI inclination = [( SMI/SMI)/duration of the interval between imaging visits]. Patients were then divided into two groups: a “steep” group (SMI inclination < -0.01) and a “gentle” group (SMI inclination ≥ -0.01). Kaplan-Meier curves and multivariate Cox proportional hazards regression models were used to evaluate the relationship between SMI inclination and overall survival (OS). Results: There were no differences in patient characteristics between the two groups with respect to median age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), disease control rate or first-line treatment regimen. OS from the start of second-line GD therapy group was significantly shorter in the “steep” group relative to the “gentle” group. The multivariate analysis revealed that “steep” SMI inclination and presence of anemia were strong predictors of poor prognosis. Conclusion: Higher values of SMI inclination, indicating a faster rate of skeletal muscle mass reduction, may serve as a useful predictive marker for OS in mUC patients undergoing second-line GD chemotherapy.     

放化疗对局部晚期非小细胞肺癌患者外周血VEGF的影响

目的 探讨Ⅲ期非小细胞肺癌患者采用同步放化疗治疗的临床疗效及对患者外周血VEGF、生存期的影响.方法 按照随机抛硬币法将74例Ⅲ期非小细胞肺癌患者分组为对照组(序贯放化疗)与观察组(同步放化疗),分别为37例.随访6 ～ 60个月,平均为(42.6±9.4)个月.统计两组患者临床疗效、生存时间及治疗期间所产生的不良反应,采用酶联免疫法检测两组患者治疗前、后外周血VEGF水平.结果 观察组临床治疗有效率为67.57％,明显高于对照组(48.65％),P＜0.05;观察组平均生存时间为(19.9±4.1)个月,明显长于对照组[(12.5±3.4)个月],P＜0.05.两组主要不良反应为消化道反应和骨髓抑制剂放射性食管炎,但两组不良反应发生率比较,P＞0.05.治疗后,观察组外周血VEGF水平较治疗前显著下降,对照组较治疗前显著升高,两组患者改善程度与治疗前比较,P＜0.05;然而观察组优于对照组,P＜0.05.结论 应用同步放化疗治疗Ⅲ期非小细胞肺癌疗效显著且安全;此外,同步放化疗可降低患者因化疗所诱导的外周血VEGF表达,从而降低患者外周血VEGF水平,抑制肿瘤增殖及转移.     

Prognostic Significance of Pancreatic Metastases in Patients With Advanced Renal Cell Carcinoma Treated With Systemic Therapy

BackgroundPancreatic metastases (PM) are rare in renal cell carcinoma. It has been suggested that patients with metastases to the pancreas have a more favorable prognosis, but little is known about the long-term outcomes with systemic therapy. We sought to understand the outcomes of patients with metastatic renal cell carcinoma with PM treated with systemic therapy.Patients and MethodsWe conducted a pooled analysis of 4736 patients with metastatic renal cell carcinoma treated on phase II/III clinical trials. Systemic therapies included anti-vascular endothelial growth factor targeted therapy, mammalian target of rapamycin-targeted therapy, and cytokine therapy.ResultsThe primary end point was overall survival (OS) in patients with versus without PM. Statistical analyses were performed using Kaplan-Meier analysis and Cox regression. Among 4736 patients, 235 (5.0%) were identified to have baseline PM at therapy initiation. The median OS in patients with PM was significantly prolonged with OS of 41.7 months versus 19.0 months (adjusted hazard ratio, 0.52; P < .0001). Similarly, progression-free survival was significantly prolonged in patients with PM (10.9 vs. 6.9 months; adjusted hazard ratio, 0.72; P = .004). The effect of PM on OS and progression-free survival was independent of other sites of metastasis or International mRCC Database Consortium risk group.ConclusionThe presence of PM in RCC is an independent positive predictor for survival and improved response to systemic therapy. These findings suggest RCC with PM is associated with favorable outcomes and further work to understand the underlying disease biology of these patients is warranted.     

Prognostic Significance of HER2 Expression Changes Following Neoadjuvant Chemotherapy in Saudi Patients With Locally Advanced Breast Cancer

BackgroundProgesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) significantly influence disease prognosis and therapeutic response in patients with breast cancer. Neoadjuvant chemotherapy (NACT) can change the receptor status, affecting the disease characteristics.Patients and MethodsA retrospective chart review was carried out at a single tertiary care hospital in Riyadh, Kingdom of Saudi Arabia, from December 2008 to December 2014, where 91 adult female patients diagnosed with locally advanced breast cancer planning to receive NACT were included. Original pathology and surgical histopathology reports were assessed, and patients were followed up to recurrence, death, or until December 2019. An expression for the ER, PR, and HER2 was carried out in pre and post NACT specimens by an experienced pathologist, and all HER2 with 2+ immunohistochemistry was sent for fluorescence in situ hybridization as per American Society of Clinical Oncology guidelines.ResultsER pre- and postoperatively changed from positive to negative in 17.6% of patients and from negative to positive in 1.1% of patients (P < .001). ER status remained stable in 81.3% of patients. PR changed from positive to negative in 13.2% of patients, and from negative to positive in 3.3% of patients (P < .001), whereas it remained stable in 83.5% of patients. HER2 changed from positive to negative in 11% of patients, and from negative to positive in 5.5% of patients (P < .001), and it remained stable in 83.5% of patients. No significant association was found between overall survival and disease-free-survival with HER2 expression change.ConclusionNACT can induce changes in the ER, PR, and HER2 status, which should be evaluated post-NACT to choose the optimal treatment regimens.     

TPS1新辅助化疗对局部晚期鼻咽癌的疗效观察

目的 研究局部晚期鼻咽癌使用TPS1新辅助化疗的ORR及不良反应,探讨TPS1替代TPF新辅助化疗的可能性.方法 对29例局部晚期鼻咽癌,使用TPS1新辅助化疗2个周期后行同步放化疗.结果 TPS1新辅助化疗后BMI(体重指数)变化中位数0.34(0~1.1),总体放化疗后BMI(体重指数)变化中位数1.1(0.73~2.11).新辅助化疗后鼻咽部即时疗效评价:CR 4例(13.8%),PR 24例(82.8%),SD 1例(3.4%),ORR 96.6%.总体放化疗后鼻咽部即时疗效评价:CR 22例(75.9%),PR 7例(24.1%),ORR 100.0%.TPS1新辅助化疗后全组无4级不良反应,罕见3级不良反应,大多为0~1级不良反应,2级反应主要为恶心(48.0%),呕吐(21.0%),白细胞减少(24.0%)和中性粒细胞减少(14.0%).整体放化疗结束后全组无4级不良反应,少见3级不良反应(口腔黏膜炎除外).主要急性毒副作用表现为血液毒性,放射性皮炎,口腔黏膜炎,口干,脱发和呕吐.结论 对局部晚期鼻咽癌使用TPS1新辅助化疗有很好的近期疗效及较低的毒副反应,TPS1有替代TPF方案的可能.     

Circulating Biomarkers in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus in the Pre-nephrectomy Setting

Many drugs are available in renal cell carcinoma (RCC), yet clinicians are still looking for predictive biomarkers of disease recurrence or progression supporting more personalised treatments. An assessment of circulating biomarkers over time was carried out in this French, open-label, single-arm, multicentre trial conducted in 25 patients with either locally advanced (n = 14) or metastatic RCC (n = 11) who received everolimus (10 mg daily) for 6 weeks prior to nephrectomy (NEORAD, NCT01715935). Circulating biomarkers, including circulating tumour cells, haematopoietic and endothelial cells, plasma angiogenesis and inflammatory markers were quantified at baseline, upon everolimus and post-nephrectomy. We assessed tumour burden, objective response rate upon RECIST1.1, disease-free survival (DFS) and progression-free survival (PFS). The correlation between circulating biomarkers was evaluated with multiple factor analysis and biomarker association with DFS/PFS by Cox regression. No objective response rate was obtained before nephrectomy. Upon everolimus, neutrophils, platelets and sVEGFR2 significantly decreased. We did not find any association between circulating biomarkers and DFS/PFS, but patients with the highest tumour burden at baseline had significantly higher plasma levels of interleukin-6, an inflammatory circulating biomarker, and lower levels of sVEGFR2, related to angiogenesis. Further understanding of the link between these circulating biomarkers could help to optimise drug combinations in RCC.     

晚期卵巢癌患者外周血sIL－2R的检测及临床意义

应用ＥＬＩＳＡ法对２０例晚期卵巢癌患者外周血可溶性白细胞介素２受体（ＳｏｌｕｂｌｅＩｎｔｅｒｌｅｕｋｉｎ－２Ｒｅｃｅｐｔｏｒ，ｓＩＬ－２Ｒ）进行了测定，并以２５例良性卵巢肿瘤及１５例正常人作对照。结果显示，卵巢癌患者术前ｓＩＬ－２Ｒ明显高于良性肿瘤及正常对照组，且具有显著性差异（Ｐ＜０．０５）；卵巢癌患者经手术后，血ｓＩＬ－２Ｒ含量明显降低（Ｐ＜０．０５），推测卵巢癌患者细胞免疫功能紊乱可能与ｓＩＬ－２Ｒ升高有关。     

大肠癌患者外周血微转移与化疗及预后的关系

[目的]研究大肠癌患者外周血微转移与化疗及预后的关系.[方法]选取大肠癌患者121例,应用RT-PCR技术,以CK20 mRNA为标志物,检测术前、术后第2天、首次化疗后血液微转移情况及与生存期的关系.[结果]术前血液CK20 mRNA微转移阳性率为53.7%,其中Dukes＇A、B、C、D期的阳性率分别为20%、25%、78.5%、75%,4组之间有显著性差异（χ^2=12.03,P＜0.05）.术后第2天血液CK20 mRNA微转移阳性率为59.5%,手术前后阳性率无显著性差异（χ^2=0.82,P＞0.05）.化疗前后血液CK20 mRNA阳性率差异非常显著（χ^2=25.59,P＜0.05）.Cox模型分析提示CK20 mRNA阳性表达者及化疗无效者预后不佳（P＜0.05）.[结论]化疗能降低大肠癌患者血液微转移的发生率;血液微转移提示患者预后不良.