Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer—Updated Diagnostic Utility,Sensitivity, Specificity,and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis

ContextAccurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of ⁶⁸Ga-PSMA PET in this setting.ObjectiveTo perform a systematic review and meta-analysis to update reported predictors of positive ⁶⁸Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles.Evidence acquisitionWe performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.Evidence synthesisA total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive ⁶⁸Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0–0.19, 0.2–0.49, 0.5–0.99, 1–1.99, and ≥2 ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed.ConclusionsGa-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2 ng/ml (33%) and 0.2–0.5 ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings.Patient summaryGallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.     

Immunohistochemical expression of p27kip1 in metastatic laryngeal squamous cell carcinoma

PurposeLaryngeal squamous cell carcinoma (LSCC) is an interesting diagnostic and therapeutic issue. The diagnostic delay is mainly a consequence of the lack of evident symptoms in the early stage of the disease. The purpose of current studies was the evaluation of the expression of p27^kip1 in primary and metastatic LSCC in correlation with patients’ clinicopathological data.Material/methodsThe indirect immunohistochemical studies were performed on the series of 60 sections (primary tumor: 20 cases of N(0) and 20 cases of N(+), and nodal meta: 20 cases), using primary antibody against p27^kip1 [clone 1B4]. The expression of analyzed protein was performed using automated morphometric methods.ResultsThe p27^kip1 nuclear expression was found in 100% (40/40) cases of primary tumor, and in 85% (17/20) cases of SCC meta at lymph nodes. In primary LSCC N(0) the expression of p27^kip1 was significantly higher compared to N(+) cases (p = 0.036672). However, the p27^kip1 expression in SCC metastases was higher compared to the primary SCC.Moreover, the analyses based on the classification trees revealed the cutoff p27^kip1 expression in primary LSCC (IRS ≤ 76) which was characteristic for N(+) patients. Consequently, our analysis revealed that high expression of p27^kip1 (IRS > 76) was characteristic for N(0) patients.ConclusionsOur results suggest that p27^kip1 might be useful prognostic factor of metastatic potential in laryngeal squamous cell carcinoma.     

Metastatic incidence of (PET)CT positive lung hilar and retroperitoneal lymph nodes in esophageal cancer patients

BackgroundExtra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions.MethodsAll patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012–December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates.ResultsFrom 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up.ConclusionsThe majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.     

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H₀: 55% and H₁= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.     

Androgen Receptor Splice Variant,AR-V7, as a Biomarker of Resistance to Androgen Axis-Targeted Therapies in Advanced Prostate Cancer

Many therapeutic options are now available for men with metastatic castration-resistant prostate cancer (mCRPC), including next-generation androgen receptor axis-targeted therapies (AATTs), immunotherapy, chemotherapy, and radioisotope therapies. No clear consensus has been reached for the optimal sequencing of treatments for patients with mCRPC, and few well-validated molecular markers exist to guide the treatment decisions for individual patients. The androgen receptor splice variant 7 (AR-V7), a splice variant of the androgen receptor mRNA resulting in the truncation of the ligand-binding domain, has emerged as a biomarker for resistance to AATT. AR-V7 expression in circulating tumor cells has been associated with poor outcomes in patients treated with second- and third-line AATTs. Clinically validated assays are now commercially available for the AR-V7 biomarker. In the present review of the current literature, we have summarized the biology of resistance to AATT, with a focus on the AR-V7; and the clinical studies that have validated AR-V7 expression as a strong independent predictor of a lack of clinical benefit from AATTs. Existing evidence has indicated that patients with AR-V7–positive mCRPC will have better outcomes if treated with taxane chemotherapy regimens rather than additional AATTs.     

Effectiveness of craniotomy and long-term survival in 35 patients with gestational trophoblastic neoplasia with brain metastases: a clinical retrospective analysis

ObjectiveTo investigate the clinical characteristics, treatments, and prognostic factors among patients with gestational trophoblastic neoplasia (GTN) exhibiting brain metastases who underwent craniotomy.MethodsThirty-five patients with GTN who had brain metastases and subsequently underwent craniotomies between January 1990 and December 2018 at Peking Union Medical College Hospital were identified using the GTN database. Their clinical manifestations, treatments, outcomes, and prognostic factors were retrospectively analyzed.ResultsAll 35 patients underwent decompressive craniotomy, hematoma removal, and metastatic tumor resection combined with multiagent chemotherapy. Eighty percent (28/35) achieved complete remission, 11.4% (4/35) achieved partial remission, and 8.6% (3/35) had progressive disease. Not counting 2 patients who were lost to follow-up, 81.8% of the patients (27/33) were alive after a median follow-up of 72 months. The 5-year overall survival rate was 80.4%. Univariate analysis revealed that a history of chemotherapy failure (p=0.020) and a >1-week interval between craniotomy and chemotherapy commencement (p=0.027) were adverse risk factors for survival. Multivariate analysis showed that previous chemotherapy failure remained an independent risk factor for poor survival (odds ratio=11.50; 95% confidence interval=1.55–85.15; p=0.017).ConclusionDecompressive craniotomy is a life-saving option if metastatic hemorrhage and intracranial hypertension produce a risk of cerebral hernia in patients with GTN who have brain metastases. Higher survival rates and improved prognoses can be achieved through perioperative multidisciplinary cooperation and timely standard postoperative chemotherapy.     

胃癌淋巴结大小与转移的探讨

目的　本文通过胃癌淋巴结病理与CT对照 ,讨论根据淋巴结大小 (以 >10mm为标准 )判断淋巴结转移的可靠性。方法　 2 4例胃癌切除和D1或D2 淋巴结清除以及术前CT检查 ,分别记录淋巴结直径大小、数量和转移阳性率。结果　 2 4例胃癌手术摘取淋巴结 3 95个 ,病理证实 12 3个 (3 1% )淋巴结转移阳性。10mm以下的淋巴结占 76% ,其中 5 6%的淋巴结转移阳性 ,1～ 5mm和 6～ 9mm淋巴结转移率分别为 8%和 46% ;10mm或以上淋巴结转移阳性率分别为 5 4%和 68%。CT检出淋巴结 174个 ,病理证实 71个 (4 1% )淋巴结转移阳性。小于 10mm淋巴结占 3 8% ,1～ 5mm和 6～ 9mm淋巴结转移率分别为 17%和 3 1% ;10mm以上淋巴结转移阳性 5 0 %～ 76%。结论　胃癌小淋巴结转移率也较高 ,CT影像单纯依据淋巴结大小判断淋巴结转移是不可靠的。     

肝转移癌的DSA表现及介入性治疗

目的　研究肝转移癌ＤＳＡ表现及血管内介入治疗效果。材料和方法　５１例肝转移癌均行肝动脉造影,再行抗癌药物灌注或栓塞。结果　富血供型 ２０例（３９．２％）,等血供型 ９例（１７．７％）,乏协供型 ２２例（４３．１％）。肿瘤形态：结节状 ３３例;囊状４例;斑片状１４例。治疗后９２．２％病人症状减轻,５６．８％的肿瘤较前缩小,半年、１年、２年、３年存活率分别为９０．２％、５２．９％、２２．６％及１２．５％。结论　ＤＳＡ及其介入性治疗为肝转移瘤的一种有效的诊断和非手术治疗方法。     

Sentinel Node Biopsy and Concomitant Probe-Guided Tumor Excision of Nonpalpable Breast Cancer

Background Preliminary data have shown encouraging results of a single intratumoral radiopharmaceutical injection that enables both sentinel node biopsy and probe-guided excision of the primary tumor in patients with nonpalpable breast cancer. The aim of the study was to evaluate this approach in a large group of patients. Methods Lymphoscintigraphy was performed in 368 patients with nonpalpable breast cancer after intratumoral injection of ^99mTc-nanocolloid (.2 mL, 123 MBq, 3.3 mCi) guided by ultrasound or stereotaxis. The sentinel node was pursued with the aid of vital blue dye (1.0 mL, intratumoral) and a gamma ray detection probe. In case of breast-conserving surgery, the probe was used to guide the excision. Results At least one sentinel node could be identified intraoperatively in 357 patients (97%), of whom 69 had involved nodes (19%). Age over 60 years was associated with less frequent nonaxillary lymphatic drainage and absence of internal mammary chain dissemination. Tumor-free margins were obtained in 262 (89%) of the 293 patients who underwent segmental excision. Re-excision of the primary tumor bed was performed in six patients (2%). During a median follow-up of 22 months, one breast recurrence and one axillary recurrence were observed. Conclusions Lymphatic mapping and probe-guided tumor excision of nonpalpable breast cancer by intralesional administration of a single dose of ^99mTc-nanocolloid and blue dye resulted in 97% identification of the sentinel node and in tumor-free margins in 89% of the patients who underwent breast-conserving surgery. Longer follow-up is needed to substantiate the accuracy and safety of this technique.