Adaptive radiotherapy in patients receiving neoadjuvant radiation for soft tissue sarcoma

AimThe aim of this study is to evaluate tumor volume changes during preoperative radiotherapy and to assess the role of adaptive radiation.BackgroundContemporary neoadjuvant radiotherapy utilizes image guidance for precise treatment delivery. Moreover, it may depict changes in tumor size and shape.Materials and methodsBetween 2016 and 2018, 23 patients aged ≥18 years with soft tissue sarcoma were treated with neoadjuvant radiation followed by surgical resection. The tumor volumes (cc) were measured using the Pinnacle planning system prior to starting radiotherapy and during treatment, the changes in volume and absolute differences were estimated. Moreover, patient's position on the machine was evaluated to assess setup offsets. The triggers for plan adaptation were >1 cm expansion or unacceptable setup offsets.ResultsThe mean tumors volume at presentation was 810 cc (range, 55–4000). At last cone beam CT the tumor volume had changed in 14 patients (61%); it was stable in nine patients (39%). Disease regression was documented in eight patients (35%), with median shrinkage of −20.5% (range, −2 to −29%), while tumor progression was observed in six cases (26%), the median change was 12.5% (range, +10 to +25%).Adaptive radiation was required in four patients (17%). For the remaining 19 cases (83%), the dose distribution was adequate to cover target volumes.ConclusionsChange in soft tissue sarcoma volume during radiation is not uncommon. Image guidance should be used to reduce setup errors and to detect differences in tumor volume. Image guidance and adaptive radiation are paramount to ensure optimal radiation delivery.     

Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

Background and Purpose

In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.

Materials and Method

In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression.

Results

Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.

Conclusions

Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method.     

A Comparison of Radiologic Tumor Volume and Pathologic Tumor Volume in Renal Cell Carcinoma (RCC)

Objective

To investigate the difference between preoperative radiologic tumor volume (RTV) and postoperative pathologic tumor volume (PTV) in patients who received nephrectomy for renal cell carcinoma (RCC).

Materials and Methods

We reviewed 482 patients who underwent preoperative computed tomography (CT) within 4 weeks before radical or partial nephrectomy for renal cell carcinoma. RTV measured by a three dimensional rendering program was compared with PTV (π/6ⅹheightⅹlengthⅹwidth) measured in surgical specimen according to pathologic tumor size and histologic subtype. Correlation of the inter-quartile range (IQR) of the RTV and Fuhrman nuclear grade was also investigated.

Results

There was a significant positive linear correlation between RTV and PTV (p<0.001, r = 0.911), and the mean RTV and mean PTV were not significantly different (79.0 vs 76.9cm³, p = 0.393). For pathologic tumor size (PTS) <4cm, the mean RTV was larger than the mean PTV (10.9 vs 7.1cm³, p<0.001). For a PTS of 4-7cm, the mean RTV was larger than the mean PTV (56.0 vs 44.7cm³, p<0.001). However, for a PTS ≥7cm, there was no statistical difference between RTV and PTV (p>0.05). Among patients with clear cell RCC, the mean RTV was significantly larger than the mean PTV (p = 0.042), not for non-clear cell group (p = 0.055). As the quartile of the RTV increased, the Fuhrman grade also increased (p<0.001).

Conclusions

RTV was correlated with PTV and pathologic grade. RTV was larger than the PTV for a tumor size 7 cm or less or in clear cell RCC. RTV may be useful to measure tumor burden preoperatively.     

Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study

Objective

To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC).

Methods

A total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed.

Results

Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ≥grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ≥grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2–8.9), and 32.6 months (95% CI, 27.3–63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5–10.5), and not reached yet (95% CI, 1.0–31.1) for the first-line sorafenib group, respectively.

Conclusions

Sorafenib produced tolerable safety, with a ≥grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.     

Mean nuclear area of fine needle aspirates of primary preoperative palpable breast carcinoma using image cytometry

OBJECTIVE: Early, operable breast cancers in appropriate patients are increasingly being treated preoperatively using neoadjuvant chemotherapy. A good response rate is seen with high grade tumors. Nuclear size, which may reflect the grade of the tumor, is also of possible prognostic value in breast cancer. STUDY DESIGN: We measured the mean nuclear area (MNA) of 114 consecutive preoperative fine needle aspirates of palpable, operable breast cancers. We used computerized image cytometry to measure nuclear area to determine tumor biology and possible grade prior to treatment. RESULTS: Histologic grade distribution was as follows: low grade, 15%; moderate grade, 40%; and high grade, 45%. Mann-Whitney test for trend on tumor size and histologic grade between MNA showed a significant relationship between MNA and tumor size (P=.016) but no significance between MNA and histologic grade (P =.22). The chi2 and Fisher Exact Test between MNA and node-positive or -negative patients showed no significance. CONCLUSION: When correlating MNA with tumor size and histologic grade, high MNA is present at a higher frequency as tumor size and histologic grade increase.     

术前CA125、OPN、CXCL8、NLR联合检测对乳腺癌改良根治术患者术后复发转移风险的评估价值

摘要 目的：探讨术前糖类抗原125（CA125）、骨桥蛋白（OPN）、趋化因子配体8（CXCL8）、中性粒细胞与淋巴细胞比值（NLR）联合检测对乳腺癌改良根治术患者术后复发转移风险的评估价值。方法：选取2015年4月-2016年4月期间我院收治的乳腺癌改良根治术患者384例按照术后有无复发转移分为未复发转移组（n=345）和复发转移组（n=39）,对比复发转移组、未复发转移组CA125、OPN、CXCL8、NLR,乳腺癌改良根治术患者术后复发转移的影响因素采用多因素Logistic回归分析。采用受试者工作特征（ROC）曲线来判断CA125、OPN、CXCL8、NLR检测对乳腺癌改良根治术患者术后复发转移风险的评估价值。结果：复发转移组的CA125、OPN、CXCL8、NLR高于未复发转移组,组间对比差异有统计学意义（P<0.05）。乳腺癌改良根治术患者术后复发转移与肿瘤最大直径、临床分期、术前新辅助化疗、人表皮生长因子受体2（HER2）、淋巴结转移、组织学类型、细胞增殖标志抗原（ki-67）、雌激素受体（ER）/孕激素受体（PR）、P53、术后放疗、术后内分泌治疗有关（P<0.05）。多因素Logistic回归分析结果显示：OPN偏高、CXCL8偏高、NLR偏高、肿瘤最大直径≥2 cm、淋巴结转移阳性、ER/PR双阴性、临床分期为III期、术前未接受新辅助化疗是乳腺癌改良根治术患者术后复发转移的危险因素（P<0.05）。术前CA125、OPN、CXCL8、NLR联合检测评估复发转移的曲线下面积（AUC）为0.855均高于各指标单独检测。结论：乳腺癌改良根治术后复发转移与OPN、CXCL8、NLR、肿瘤最大直径、淋巴结转移、ER/PR、临床分期、术前接受新辅助化疗均存在一定联系,临床需据此采取针对性干预措施加以防范。且术前CA125、OPN、CXCL8、NLR联合检测辅助评估术后复发转移的价值较高。     

Preoperative neoadjuvant chemoradiation for locally advanced gastric adenocarcinoma

Aims and BackgroundTo evaluate toxicity and the radical resection rate in gastric adenocarcinoma treated with preoperative neoadjuvant chemoradiation.Materials & Methods32 patients, 22 males and 10 females with gastric adenocarcinoma, were treated with chemoradiation and hyperthermia.ResultsThe neoadjuvant regimen was completed as planned in 19/32 (59 %) patients; in the remaining patients the intensity of chemotherapy had to be reduced because of haematological and gastrointestinal toxicity. Surgical stage was as follows: 2 patients pathologically complete response, 3 patients AJCC stage I.A, 5 patients stage I.B, 7 patients stage II, 7 patients stage III.A, 1 patient stage III.B, 7 patients stage IV. R0 resection was achieved in 19/32 (59%) patients, R1 in 2/32 (6%) patients and R2 in 11 (34%) patients. Downstaging after neoadjuvant chemoradiotherapy was achieved in 17/32 (53%) patients. At the date of evaluation (31 March 2009), 4 patients were still alive 58, 81, 86 and 98 months from the date of diagnosis. Median survival was 18 months (95% confidence interval: 13–38 months). One-year survival was 69% (95% confidence interval: 53%–85%). Four-year survival was 19% (95% C.I.: 5%–34%).ConclusionsPreoperative neoadjuvant chemoradiotherapy has acceptable toxicity, and can lead to a high rate of R0 resections.     

Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot‘em all!

BackgroundAbout 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients.Materials and methodsPatients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel.ResultsBetween 2015–2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52–84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1–6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3–65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27–56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded.ConclusionsSimultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.     

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

BackgroundThe optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.AimTo compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).MethodsRetrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.Results47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. “not reached” (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.ConclusionsCompared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.     

Clinicopathologica Epidemiological Characteristics and Change Tendencies of Renal Cell Carcinoma in Shanxi Province of China from 2005 to 2014

Objectives

RCC is the most common solid renal malignancy in adults worldwide. To provide the insight of clinicopathologica epidemiological characteristics and change tendencies of renal cell carcinoma (RCC), 2154 cases were collected from Shanxi Province of China, including diagnose time, age, gender, tumor size, Fuhrman grade, tumor stage, tumor location, local advance or distant metastasis and first symptom from 2005 to 2014. This retrospectively investigation, as its general objective, was to analyze the clinicopathologica epidemiological characteristics and the change tendencies of RCC.

Methods

Between 2005 and 2014, 2154 patients who were diagnosed with RCC in three large tertiary hospitals at Shanxi Province were included. The patients’ demographic features, pathological diagnoses and metastatic statuses were analyzed. Statistics methods include the chi-squared test, analysis of variance, Spearman’s correlation analysis, Logistic regression and ARIMA modeling.

Results

Of the 2154 included patients, the constituent ratio of female /male was 63.1% and 36.9%, with the median age of 57 years old. Fuhrman grade distributions differed significantly between males and females (p = 0.024). Also, a significant difference in tumor size was found by different clinical stages (p < 0.001), with a linear correlation (p < 0.001). Moreover, Spearman’s analysis indicated tumor grade has a negative correlation with female (p = 0.009) and a positive correlation with tumor size (p = 0.000). It was found that the tumor diameter is bigger in the left side (p = 0.022). Furthermore, the metastasis rate was higher in the bigger tumor (p < 0.001) and the left-sided tumors (p = 0.027). Logistic regression also showed that tumor size is a risk factor for metastasis (OR = 1.724). The risk of local advance or distant metastasis in the left kidney was 1.6-fold greater than that of the right kidney. From 2005 to 2014 the number of RCC cases gradually increased (mainly for pathological grade II and III, but grade I and IV), while the average tumor size decreased, showing the severity increase mildly. Base on the results of a time series analysis-prediction the average RCC size would continue to decrease from the first quarter of 2015 to the fourth quarter of 2016.

Conclusions

The cases of RCC increased from 2005 to 2014 with clear cell type as the main pathological type in this population. The characteristics in the constituent ratios of the RCC vary depending on gender, pathological grade, tumor size, and location, which may be the important factors impacting treatment and prognosis.     

Long-Term Prognostic Analysis after Endoscopic Endonasal Surgery for Olfactory Neuroblastoma: A Retrospective Study of 13 Cases

ObjectivesTo summarize the characteristics and long–term outcomes of olfactory neuroblastoma through the analysis of 13 cases in single institution, with the assessment of treatment modality, prognostic factors.MethodA retrospective study of thirteen cases diagnosed as olfactory neuroblastoma and underwent combined treatments during the period 2000–2010. Statistical analysis was performed to search for prognostic factors and compared different treatment modalities.Results13 patients were enrolled in this study, including 8 male and 5 female, ranging from 15 to 69 (median 43) years old. One patient at stage A was only treated with endoscopic endonasal surgery (EES). Seven patients were treated with preoperative radiotherapy and EES, two with EES and postoperative radiotherapy, and the other three with combined radiotherapy and chemotherapy. The range of follow-up time varied from 23 to 116 months (median 65 months). The 5-year overall survival rate was 46.2% (6/13). To date, these thirteen patients have not suffered local recurrences while two patients had lymph node recurrences and one had distant metastasis in the bone marrow. In 13 patients, 61.5% were diagnosed as late T stage (T3/4), 69.2% late Kadish stage (C/D) and 53.8% were high Hyams grade (I/ II), which indicated poor prognosis. Related prognostic factors were the TNM stage (T stage P = 0.028, N stage P = 0.000, M stage P = 0.007), Kadish stage (P = 0.025) and treatment modality (P = 0.015).ConclusionLate stage of TNM and Kadish staging system indicated a poor prognosis. Combined treatment modality, including endoscopic endonasal surgery, achieved a better outcome than non-surgical approach.     

Partial nephrectomy vs cryoablation for T1a renal cell carcinoma: A comparison of survival benefit stratified by tumour size

ObjectiveWe compared the impact on survival outcomes of partial nephrectomy (PN) and cryoablation (CA) for patients diagnosed with T1a renal cell carcinoma (RCC).Patients and MethodsAmong patients diagnosed between 2004 and 2014 in the Surveillance, Epidemiology and End Results program, we identified histologically confirmed T1aN0M0 RCC treated with PN (n = 17644) or CA (n = 868). Propensity score matching (PSM) was performed. Kaplan-Meier method, Cox proportional hazards model were used to calculate cancer specific mortality (CSM) and overall mortality (OM) in the unmatched and matched cohort, and in subgroups based on tumour size (< 2 cm, 2-3 cm, 3-4 cm). Sensitivity analyses were performed.ResultsA total of 18512 patients were identified: PN (93.88%) and CA (6.12%). In the propensity-score matched cohort, for tumours ≤ 2 cm, the CA and PN groups had similar CSM (HR: 1.41, 95% CI: 0.32–6.31, p = 0.65) and OM (HR 0.97, 95%CI: 0.47–2.01, p = 0.93). For tumours 2-3 cm, CA was associated with similar CSM (HR 1.64, 95%CI: 0.67–4.03, p = 0.28) but higher OM (HR 2.05, 95%CI: 1.35–3.11, p < 0.001), compared with PN. For tumours 3-4 cm, CA was associated with increased CSM (HR: 3.76, 95% CI: 1.62–8.69, p = 0.002) and OM (HR 2.17, 95%CI: 1.48–3.18, p < 0.001).ConclusionFor RCC ≤ 2 cm, PN and CA are equal in survival outcomes. For RCC 2-4 cm, PN may have a possible advantage over CA.     

Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway

Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib treatment. Therefore, it is critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified that a long noncoding RNA GAS5 was downregulated in sorafenib nonresponsive RCCs. GAS5 overexpression conferred sorafenib sensitive to nonresponsive RCC cells, whereas knockdown of GAS5 promoted responsive RCC cells resistant to sorafenib treatment in vitro and in vivo. Mechanistically, GAS5 functioned as competing endogenous RNA to repress miR-21, which controlled its down-stream target SOX5. We proposed that GAS5 was responsible for sorafenib resistance in RCC cells and GAS5 exerted its function through the miR-21/ SOX5 axis. Our findings suggested that GAS5 downregulation may be a new marker of poor response to sorafenib and GAS5 could be a potential therapeutic target for sorafenib treatment in RCC.     

Sequential administration of interferon γ and interleukin-2 in metastatic renal cell carcinoma: results of a phase II trial

Background: Because of the known efficacy of several cytokines in the treatment of advanced renal cell cancer (RCC), we have conducted a phase II trial of the efficacy and toxicity of subcutaneous interferon γ (IFNγ) and interleukin-2 (IL-2). Methods: 63 patients with progressive metastatic RCC were treated with 100 μg recombinant IFNγ1b administered three times weekly during weeks 1 and 2 and with 4.5 MU recombinant IL-2 administered on 4 consecutive days during weeks 3 and 4, every 6 weeks. Results: 11% of patients had an objective response (CR: 3%, PR: 8%), 33% had SD. Toxicity was generally mild. The median duration of remissions (CR + PR) was 9.6 months; the median duration of SD 8 months. A significant survival benefit was evident at a median observation time of 51 months for patients (44%) responding to therapy (P < 0.0001). Conclusions: we conclude that sequential treatment with IFNγ and IL-2 may prolong survival in patients with metastatic RCC responding to therapy. Received: 2 April 2000 / Accepted: 21 April 2000     

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer

ObjectiveTo determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC).MethodsThis retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models.ResultsPostoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines.ConclusionMore than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.     

乳腺癌患者新辅助化疗后ER、PR、HER2、Ki67表达变化及临床意义

目的:研究乳腺癌患者在新辅助化疗后ER、PR、HER2、Ki67的变化及临床意义。方法:选择2012年1月-2017年12月至我院进行乳腺癌新辅助化疗的患者176例进行临床研究。所有患者化疗前及术后行经B超引导下核芯针穿刺取病理活检,检测ER、PR、Ki67、HER2的表达,分析其变化情况。结果:176例乳腺癌患者新辅助化疗前ER阳性为57例,新辅助化疗后ER阳性为69例,新辅助化疗前ER阴性为119例,新辅助化疗后ER阴性107例;新辅助化疗前后状态改变了34例(19.32%),其中12例新辅助化疗前ER阴性转变为ER阳性,22例新辅助化疗前ER阳性转变为新辅助化疗后ER阴性,化疗前后患者ER表达变化有统计学差异(x~2=8.044,P=0.037);176例乳腺癌患者新辅助化疗前PR阳性为83例,新辅助化疗后PR阳性为89例,新辅助化疗前PR阴性为93例,新辅助化疗后PR阴性87例;新辅助化疗前后状态改变了82例(46.59%),其中45例新辅助化疗前PR阴性转变为PR阳性,37例新辅助化疗前PR阳性转变为新辅助化疗后PR阴性,化疗前后患者PR表达变化有统计学差异(x~2=6.311,P=0.049);176例乳腺癌患者新辅助化疗前HER2阳性为31例,新辅助化疗后HER2阳性为30例,新辅助化疗前HER2阴性为145例,新辅助化疗后HER2阴性146例;新辅助化疗前后状态改变了3例(1.70%),其中1例新辅助化疗前HER2阴性转变为HER2阳性,2例新辅助化疗前HER2阳性转变为新辅助化疗后HER2阴性,化疗前后患者HER2表达变化无统计学差异(x~2=0.522,P=0.945);176例乳腺癌患者新辅助化疗前Ki67阳性为104例,新辅助化疗后Ki67阳性为95例,新辅助化疗前Ki67阴性为72例,新辅助化疗后Ki67阴性81例;新辅助化疗前后状态改变了109例(61.93%),其中54例新辅助化疗前Ki67阴性转变为Ki67阳性,55例新辅助化疗前Ki67阳性转变为新辅助化疗后Ki67阴性,化疗前后患者Ki67表达变化有统计学差异(x~2=2.936,P=0.048),经过新辅助化疗后,Ki67出现上调表达最高,为23.86%,同时也是下调表达最高,为38.07%。HER2表达保持不变最高,为98.30%。结论:新辅助化疗会对乳腺癌患者ER、PR、Ki67的表达造成影响,其中对Ki67的影响最为显著。     

A Systematic Review of the Efficacy and Safety Experience Reported for Sorafenib in Advanced Renal Cell Carcinoma (RCC) in the Post-Approval Setting

Background

Sorafenib was FDA approved in 2005 for treatment of renal cell carcinoma (RCC) based on the results of the pivotal phase 3 clinical trial, TARGET (Treatment Approaches in Renal Cancer Global Evaluation Trial). Since that time, numerous clinical studies have been undertaken that substantially broaden our knowledge of the use of sorafenib for this indication.

Methods

We systematically reviewed PubMed, Web of Science, Embase, Cochrane Library, and www.clinicaltrials.gov for prospective clinical studies using single agent sorafenib in RCC and published since 2005. Primary endpoints of interest were progression-free survival (PFS) and safety. PROSPERO International prospective register of systematic reviews #CRD42014010765.

Results

We identified 30 studies in which 2182 patients were treated with sorafenib, including 1575 patients who participated in randomized controlled phase 3 trials. In these trials, sorafenib was administered as first-, second- or third-line treatment. Heterogeneity among trial designs and reporting of data precluded statistical comparisons among trials or with TARGET. The PFS appeared shorter in second- vs. first-line treatment, consistent with the more advanced tumor status in the second-line setting. In some trials, incidences of grade 3/4 hypertension or hand-foot skin reaction (HFSR) were more than double that seen in TARGET (4% and 6%, respectively). These variances may be attributable to increased recognition of HFSR, or potentially differences in dose adjustments, that could be consequences of increased familiarity with sorafenib usage. Several small studies enrolled exclusively Asian patients. These studies reported notably longer PFS than was observed in TARGET. However, no obvious corresponding differences in disease control rate and overall survival were seen.

Conclusions

Collectively, more recent experiences using sorafenib in RCC are consistent with results reported for TARGET with no marked changes of response endpoints or new safety signals observed.     

Cystic Lymph Nodes in the Lateral Neck As Indicators of Metastatic Papillary Thyroid Cancer

ObjectiveTo determine whether radiographic findings portend to metastatic disease in patients with papillary thyroid carcinoma (PTC) and whether cystic lymph node metastasis can be recognized by preoperative, ultrasound-guided fine-needle aspiration (FNA).MethodsWe performed a retrospective review of patients with cystic lymph nodes in the lateral neck identified on preoperative ultrasonography between March 1996 and December 2009. Factors examined included demographic information; stage; cytologic and final pathologic findings; and imaging characteristics including location, size, and presence of vascularity and calcifications. Time of cystic node identification in relationship to initial diagnosis was also recorded.ResultsThirty patients had cystic lymph nodes in the lateral neck on cervical ultrasonography during the study period. Among this group, 28 (93%) had PTC, 1 (3%) had papillary serous carcinoma of the ovary, and 1 (3%) had poorly differentiated thyroid cancer. Median age at initial cancer diagnosis was 41 years (range, 16-64 years). Twenty-one patients (70%) were women, and median lymph node size was 1.8 cm (range, 0.6-4.8 cm). Twenty-three patients (77%) had a solitary cystic lymph node, and the remainder had more than 1 cystic lymph node. Cystic lymph nodes were identified at initial presentation in 11 patients (37%), while cystic lymph nodes were discovered in 19 patients (63%) after the initial operation. FNA was performed on the cystic lymph nodes of 23 patients (77%). Cytologic findings were positive for metastatic disease in 18 of 23 patients (78%). Among the 5 of 23 patients with negative cytologic findings, thyroglobulin aspirate was obtained in 1 patient, confirming metastatic PTC. Final pathologic review after surgical resection of cystic lymph nodes with negative cytologic findings from FNA was consistent with metastatic disease in 4 of 5 patients (80%).ConclusionsIn patients with PTC, the presence of a cystic lymph node by ultrasonographic examination is highly suggestive of locally metastatic disease. Confirmation of metastatic PTC may sometimes be achieved with thyroglobulin aspirate from cystic lymph nodes when cytologic findings are negative. Clinicians should strongly consider surgical lymph node resection of cystic lymph nodes regardless of the preoperative cytologic findings by FNA. (Endocr Pract. 2011;17:240-244)     

Pretreatment CT and PET radiomics predicting rectal cancer patients in response to neoadjuvant chemoradiotherapy

BackgroundThe purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T).Materials and methodsAn exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET.ResultsThe patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1–3; 91% accuracy in predicting TRG 0–1 vs. TRG 2–3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores.ConclusionThe pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation.