18F-FLT PET/CT在弥漫大B细胞淋巴瘤诊断及分期中的价值

本研究旨在比较18F-FLT PET/CT与CT对弥漫大B细胞淋巴瘤(DLBCL)的诊断及分期的评估价值,分析DLBCL病灶的18F-FLT PET/CT显像及分布特点。收集2008年9月至2009年12月在本院经病理确诊的36例DLBCL患者,以18F-FLT PET/CT及CT扫描全身及头颅,用18F-FLT PET/CT及CT测量原发肿瘤的部位、大小及SUVmax,计算与主动脉弓血池SUVmax比值(T/MB)。结果表明,18F-FLT PET/CT及CT检测DLBCL病灶的一致率为79.10%,其敏感性分别为96.65%、85.44%,特异性分别为100%、57.14%,阳性预测值分别为100%、96.70%,阴性预测值分别为61.11%、21.05%,假阳性率分别为0%、42.86%,假阴性率分别为3.35%、14.56%,准确率分别为96.82%、83.64%。以上指标组间比较均有统计学差异(P<0.01)。结论:18F-FLT PET/CT对DLBCL检测的敏感性、特异性均明显好于CT,能够协助DLBCL准确分期,18F-FLT与18F-FDG PET/CT显像比较尚待进一步研究证实。     

Imaging Uterine Cervical Cancer with FDG-PET/CT: Direct Comparison with PET

Purpose  To compare 2-deoxy-2-[F-18]fluoro-d-glucose–positron emission tomography (FDG-PET) and PET/computed tomography (CT) for certainty of image interpretation and for diagnostic accuracy in patients with primary and metastatic uterine cervical cancer. Materials and Methods  Images of 13 patients with cervical cancer having PET/CT examinations were reviewed retrospectively. PET and PET/CT images of all cases were read blindly and randomly by two readers. Foci of increased FDG uptake on PET or PET/CT were classified using a scoring system regarding lesion localization and characterization. PET and PET/CT findings were assessed with all clinical information available, and diagnostic accuracy was determined on a per-lesion and on a per-patient basis. Results  For both readers, PET/CT provided significantly higher frequencies of definite lesion localization (>30% higher) and definite lesion characterization (>20% higher) compared to the findings on PET alone. The improvement in lesion localization to the definite level by PET/CT provided the definite lesion characterization in at least 50% of cases. PET/CT tended to exhibit higher diagnostic accuracy than PET alone on a lesion-based analysis (92% vs. 78% in reader 1 and 92% vs. 82% in reader 2, respectively). Metastatic disease spread was, however, almost equally evaluated between PET and PET/CT. Conclusion  PET/CT was demonstrated to be useful in the definite localization and characterization of foci of increased FDG uptake, which provided its higher diagnostic accuracy than PET alone. PET/CT appears preferable to PET in the evaluation of cervical cancer, although additional study is needed.     

Prognostic significance of clinical characteristics and 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters in patients with primary mediastinal B-cell lymphoma

ObjectivePrimary mediastinal B-cell lymphoma (PMBCL) lacks standard treatment regimens. This study aimed to identify the disease’s clinical features and prognostic factors.MethodsThis retrospective study included 56 patients with PMBCL. Patient demographic details and clinicopathological characteristics were summarized, and their effects on progression-free survival (PFS) and overall survival (OS) were analyzed.ResultsThe median patient age was 29 years (range, 14–56). Twenty-two patients received DA-EPOCH-R (dose-adjusted etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone, as well as rituximab), and 34 patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Clinical/laboratory parameters, overall response rates, and 5-year PFS and OS rates did not differ between the treatment groups. Kaplan–Meier analysis indicated that late-stage disease and a higher International Prognostic Index (IPI) were associated with shorter PFS and OS. Furthermore, patients with B symptoms and first-line treatment non-responders exhibited worse OS. ¹⁸Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters, such as higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were corrected with shorter PFS.ConclusionsThis study revealed that stage IV disease, higher IPI, and B symptoms were poor prognostic factors in patients with PMBCL. Significantly, higher MTV and TLG portended worse PFS.     

2-Deoxy-2-[18F]fluoro-d-glucose-Positron Emission Tomography and Positron Emission Tomography/Computed Tomography Diagnosis of Patients with Recurrent Papillary Thyroid Cancer

Objective 2-Deoxy-2-[F-18]fluoro-d-glucose positron emission tomography (FDG-PET) has an established role in restaging of various cancers, including papillary and undifferentiated thyroid carcinoma, but detection rates are variable in the published literature. We were therefore prompted to review our experience with FDG-PET in detection of recurrent papillary thyroid cancer (PTC).Methods This is a retrospective study (April 1, 1995–March 31, 2005) of 21 patients with histologic diagnosis of PTC who had PET examinations. The group included seven men and 14 women, with age range of 26–75 years (average 50 ± 16). The PET scan request was triggered by rising levels of thyroglobulin (Tg) in the presence of a negative iodine-131 scan.Results Recurrent/metastatic disease was identified by PET in 16 (76%) of the 21 patients with PTC. The sensitivity and specificity of FDG-PET for disease detection in this cohort were 88.2% [95% confidence interval (CI), 65.7–96.7] and 75% (95% CI, 30.1–95.4), respectively. The Tg levels were 1.0–10.4 ng/ml (average, 4.52 ng/ml) in the patients with negative PET scans and 1.0–38 ng/ml (average, 16.8 ng/ml) in patients with positive scans. The lesions were located in the cervical lymph nodes (8), thyroid bed (4), lungs (4), and mediastinal lymph nodes (2).Conclusion Our study confirms the feasibility of PET in detection of residual/recurrence of PTC, with sensitivity of 88.2% (95% CI, 65.7–96.7) and specificity of 75% (95% CI, 30.1–95.4). Detectable levels of Tg, even in the presence of negative I-131 scan or anatomic imaging, should prompt restaging with FDG-PET.     

2-Deoxy-2-[F-18]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose Positron Emission Tomography/Computed Tomography in the Management of Melanoma

Objectives 2-Deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single exam. The role of FDG-PET is proven in a variety of cancers, including melanoma, but the estimates of sensitivity and specificity are based in the majority of the published studies on dedicated PET, not PET/CT. Therefore, we were prompted to review our experience with FDG-PET/CT in the management of melanoma. Methods This is a retrospective study on 106 patients with melanoma (20–87 years old; average: 56.8 ± 15.9), who had whole-body FDG-PET/CT at our institution from January 2003 to June 2005. Thirty-eight patients (35.9%) were women and 68 patients (64.1%) were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. Results All patients had the study for disease restaging. The primary tumor depth (Breslow’s thickness) at initial diagnosis was available for 76 patients (71.7%) and ranged from 0.4 to 25 mm (average: 3.56 mm). The anatomic level of invasion in the skin (Clark’s level) was determined for 70 patients (66%): 3, level II; 13, level III; 43, level IV; 11, level V. The administered dose of ¹⁸F FDG ranged from 9.8 to 21.6 mCi (average: 15.4 ± 1.8 mCi). FDG-PET/CT had a sensitivity of 89.3% [95% confidence interval (CI): 78.5–95] and a specificity of 88% (95% CI: 76.2–94.4) for melanoma detection. Conclusion This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk melanoma, prior to selection of the most appropriate therapy.     

F-18 FDG PET/CT在继发性噬血细胞综合征中的临床价值研究

本研究旨在探讨F-18 FDG PET/CT在噬血细胞综合征（HPS）的诊断和预后判断中的作用。回顾性分析了11例行F-18 FDG PET/CT检查的HPS患者,评估了F-18 FDG PET/CT对HPS相关的恶性肿瘤的诊断价值,计算了骨髓和脾脏的最大标准摄取值（SUVmax）,对骨髓和脾脏的SUVmax与HPS的多个实验室参数以及临床转归的关系进行了分析。结果表明：11患者中4例伴恶性肿瘤;通过F-18 FDG PET/CT检测判断HLH患者是否伴有恶性肿瘤的敏感性、特异性和准确性分别为100.0%、66.7%和75.0%;骨髓和脾脏的SUVmax与实验室参数无显著的相关性;预测患者预后的脾脏SUVmax值和骨髓SUVmax值的最佳截断点分别为3.10和3.47;单因素分析提示,骨髓和脾脏中F-18 FDG高摄取患者的存活时间较短。结论：F-18 FDG PET/CT在继发性HPS的病因诊断和预后判断中具有重要作用。     

18F-FDG PET/CT显像在不明原发癌中的诊断价值

目的探讨18F-FDG PET/CT在不明原发癌(CUP)患者中的临床作用。方法选择2018年3月~2019年8月经临床诊断为CUP的121例患者,其中男性79例、女性42例,年龄30~86岁(63±12岁),回顾性分析其全身18F-FDG PET/CT显像结果。本研究的最终诊断均通过病理证实或临床随访证实。结果18F-FDG PET/CT显像成功在121例患者中检出原发性肿瘤59例(49%)。18F-FDG PET/CT显像检测出最常见的原发肿瘤是肺癌(n=31)。1例患者在18F-FDG PET/CT显像中发现两种原发性肿瘤(前列腺癌和结肠癌),肺活检显示此患者为前列腺癌,结肠癌被认为是同步的第二原发肿瘤。11例18F-FDG PET/CT显像结果为假阳性。51例患者在18F-FDG PET/CT显像中未能检测到任何原发肿瘤病灶,其中有11例患者在临床随访中检测到原发肿瘤病灶,因此认为假阴性。18F-FDG PET/CT检测原发性肿瘤的敏感性、特异性和准确性分别为84%、78%和82%。结论全身18F-FDG PET/CT显像是检测CUP病灶原发肿瘤的可靠方法。除了发现原发性肿瘤外,还可帮助确定疾病的程度,并有助于患者的临床管理。      

Detection of Occult Medullary Thyroid Cancer Recurrence with 2-Deoxy-2-[F-18]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose-PET and PET/CT

Purpose 2-Deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET) has an established role in restaging of various cancers, including papillary and undifferentiated thyroid carcinoma. However, controversies exist regarding its ability to reliably assess recurrent medullary thyroid cancer (MTC). We were therefore prompted to review our experience with FDG-PET for detection of occult MTC. Methods This is a retrospective study (Apr 1, 1997–Mar 31, 2004) of 13 patients with histologic diagnosis of MTC, who had PET examinations. The group included six men and seven women, 15–62 years old (average: 48 ± 13). The PET scan request was triggered by rising levels of calcitonin and negative anatomical imaging studies. Results Recurrent/metastatic disease was identified by PET in seven (54%) of the 13 patients. The lesions were located in superior mediastinum (4), cervical lymph nodes (3), thyroid bed (2), lung (1) and liver (1). The calcitonin levels ranged from 52 to 5,090 pg/ml (average: 1,996 pg/ml) in patients with negative PET scans and from 132 to 9,500 pg/ml (average: 3,757 pg/ml) in patients with positive studies. The sensitivity and specificity of FDG-PET for disease detection in this cohort were 85.7% (95% CI: 48.7–97.4) and 83.3 % (95 % CI: 43.6–96.9), respectively. Conclusion Our findings suggest a significant role for FDG-PET in patients with suspected MTC recurrence, with sensitivity of 85.7% and specificity of 83.3% for disease detection. FDG-PET provides additional information in a significant fraction of cases (54%) and could be used for restaging of patients with MTC and elevated levels of biomarkers (calcitonin). Additional studies are necessary to further evaluate the role of FDG-PET in MTC.     

Merkel Cell Carcinoma: Is there a Role for 2-Deoxy-2-[F-18]fluoro-d-glucose-Positron Emission Tomography/Computed Tomography?

Purpose 2-Deoxy-2-[F-18]fluoro-d-glucose (FDG)–positron emission tomography (PET)/computed tomography (CT) is becoming widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single study. The role of FDG-PET/CT is proven in lymphoma, melanoma, colorectal carcinoma, and other cancers. However, there are rare malignancies such as Merkel cell carcinoma that can potentially be evaluated with PET/CT. We were therefore prompted to review our experience with FDG-PET/CT in the management of patients with Merkel cell carcinoma.Procedures This is a retrospective case series of six patients with Merkel cell carcinoma, 58–81 years old (average 69 ± 8.3), who had whole-body PET/CT at our institution from January 1st, 2003 to August 31st, 2005. Two patients were women and four were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.Results Twelve examinations were acquired for the six patients (one patient had six PET/CT, one patient had two PET/CT, and four patients had one PET/CT). The injected FDG doses ranged 381.1–669.7 MBq (average 573.5 ± 70.3). Four patients had the PET/CT as part of initial staging, and two patients had the exam for restaging (after surgery and XRT). A total of six Merkel lesions (pancreas, adrenal, lip, submandibular lymph nodes, cervical lymph nodes, and parapharyngeal soft tissue) were identified in three patients and confirmed on histopathological examination. The FDG uptake in these areas was intense, with maximum standardized uptake value (SUVmax) values of 5–14 (average 10.4 ± 3.8). In one patient, the PET/CT scan identified abnormal focal distal sigmoid uptake that was biopsied and diagnosed as adenocarcinoma. Two patients had negative scans and had no clinical evidence of disease on follow-up office visits (up to one year after PET/CT).Conclusions This case series suggests that FDG-PET/CT may have a promising role in the management of patients with Merkel cell carcinoma.     

PET/CT-Guided Interventions in Oncology Patients: A Nursing Perspective

In the past 5 years, the utilization of positron emission tomography/computerized tomography (PET/CT) guidance is more commonly used for cancer patients undergoing biopsy and ablations at this National Cancer Institute-designated cancer center. The interventional use of PET/CT imaging requires nurses to have a thorough understanding of the mechanisms involved to provide the best care in an environment that is safe for patients and staff. Evidence suggests cohesive care, and safe practice measures are achieved when patients actively participate and understand their care. This article will discuss how a collaborative patient-centered approach in caring for oncologic patients undergoing PET/CT interventions is necessary for achieving quality patient outcomes.     

Intrapatient Comparison of 2-Deoxy-2-[F-18]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose with Positron EmissionTomography/Computed Tomography to Tc-99m Fanolesomab (NeutroSpec) for Localization of Infection

Purpose This study evaluated the efficacy of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) in comparison with Tc-99m fanolesomab (NeutroSpec) for imaging infection. Procedures Twelve patients with possible infection were studied with both FDG-PET/CT and Tc-99m fanolesomab. One patient was studied twice for a total of 13 paired studies. The final determination of the presence or absence of infection and the site(s) of infection at the time of imaging was made by an infectious disease physician using culture results and other relevant information. The sensitivity, specificity, and accuracy were calculated for each imaging study on a per paired study basis and a per lesion basis. In addition, the quality of lesion depicted was compared between the two studies. Results Three patients were determined not to have infection. Ten paired studies, in nine patients, were determined to have one or more sites of infection: seven had one site and three had two sites. On a per paired study basis the sensitivity, specificity, and accuracy of FDG-PET/CT were all 100%; for Tc-99m fanolesomab these parameters were 30, 100, and 46%, respectively (P < 0.01 for sensitivity and accuracy). On a per site basis the results for FDG-PET/CT were all 100% and for Tc-99m fanolesomab they were 23, 100, and 38% (P < 0.01 for sensitivity and accuracy). In the three sites of infection shown by both studies, FDG-PET/CT was judged to be superior in spatial resolution and anatomic localization compared to Tc-99m fanolesomab in all three sites. Conclusion FDG-PET/CT is superior to Tc-99m fanolesomab for detecting and localizing sites of infection.     

X线平片、CT、ECT诊断骨转移瘤的比较分析

目的：比较分析X线平片、CT、发射计算体层摄影（ECT）诊断骨转移瘤。材料与方法：50例骨转移瘤均经手术病理证实,所有病例均先后作了X线摄影,CT及ECT全身骨扫描。所用仪器为东芝500mAX线机,东芝L3000CT扫描机及法国Sopha公司SDX型发射计算体层摄影仪。结果：诊断转移性骨肿瘤灵敏度：ECT（97．2％）高于CT（69．7％）、X线平片（59．3％）;精确度：ECT（88．0％）亦高于CT（78．0％）、X丝平片（68．0％）;假阴性率：ECT比X线平片、CT均低的多;特异性;ECT（64．3％）明显低于CT（94．1％）及X线平片（92．9％）;假阳性率：ECT均比CT及X线平片高。ECT的阴性预测值较高,而X线平片及CT扫描的阳性预测值较高。结论：ECT能更早显示出病灶、是骨转移瘤较好的筛选方法。X线平片、CT检查特异性较强是骨转移瘤最基本的检查方法,三种方法具有互补作用。     

Fluorine-18 fluorodeoxyglucose positron emission tomography in the management of solitary pulmonary nodule: a review

Solitary pulmonary nodules are common radiologic findings and their detection has increased due to the introduction and improvement of diagnostics. Since a nodule can be an expression of early lung cancers, a proper classification and management are required because its treatment might lead to decreased morbidity and mortality. In this regard, prominent guidelines are available although they are characterized sometimes by discordant and misleading evidences. Furthermore, the same results of studies in the literature appear conflicting. Aim of this work is to evaluate the role of imaging through an extensive literature review but focusing on 18-fluorine fluorodeoxyglucose positron emission tomography combined with computed tomography (¹⁸F-FDG-PET/CT) in order to assess the limits and future perspectives of solitary pulmonary nodule characterization in early detection of lung cancer.

• Key messages

• Detection of solitary pulmonary nodules has increased.

• Management of solitary pulmonary nodules is still debated.

• Future perspectives of early solitary pulmonary nodule characterization.

     

~(18)F-NaF PET/CT对前列腺癌骨转移的诊断价值

目的探讨18F-Na F PET/CT在前列腺癌骨转移中的诊断价值及影像学特征。方法回顾性分析42例经病理证实为前列腺癌的患者的临床资料,均行18F-Na F PET/CT骨显像。比较18F-Na F PET/CT、18F-Na F PET和单独CT诊断前列腺癌骨转移灶的灵敏性、准确性。结果18F-Na F PET/CT、18F-Na F PET、单独CT诊断前列腺癌骨转移瘤的灵敏度分别为100%、94.4%、77.8%,准确性分别为95.2%、87.0%、71.4%。18F-Na F PET/CT骨显像的准确性显著高于18F-Na F PET和单独CT(P0.05)。结论18F-Na F PET/CT对前列腺癌骨转移诊断的灵敏度、特异性、准确性较高。     

Prospective Comparison of FDG and FET PET/CT in Patients with Head and Neck Squamous Cell Carcinoma

Aim  The clinical usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) in head and neck squamous cell carcinoma (HNSCC) is now well-documented. However, its sensitivity is greater than its specificity due to false-positive results in inflammatory or infectious lesions, which are frequent in this area, in particular after treatment by surgery and/or radiotherapy. O-2-fluoro-(18F)-ethyl-L-thyrosine (FET) has been reported not to be taken up by such lesions, and a preliminary study indicated that this may be clinically useful in HNSCC. We performed a prospective study to compare the diagnostic performances of FDG and FET PET/CT in the different settings of HNSCC. Materials and Methods  Twenty-seven patients (20 men and seven women, aged 48–76, among 30 patients included) and 69 suspected cancer sites are now evaluable on basis of postsurgical histology and/or follow-up greater than 6 months; 15 patients were referred for initial staging and 12 during posttherapy follow-up, a recurrence being suspected in eight of them. FDG and FET PET/CT were performed on two different days, the patient fasting for 6 h, 1 h after injection of 5 MBq/kg of body mass of each radiopharmaceutical. Both PET/CT examinations were blind read more than 6 months after the end of inclusions in a random order for each tracer and with a time interval greater than 1 month between FDG and FET PET/CT blind readings. Results  Overall diagnostic performances, derived from blind reading: FDG PET/CT on a per patient basis: sensitivity 100%, specificity 71%, accuracy 93%; FDG PET/CT on a per site basis: sensitivity 95%, specificity 63%, accuracy 83%; FET PET/CT on a per patient basis: sensitivity 70%, specificity 100%, accuracy 78%; FET PET/CT on a per site basis: sensitivity 64%, specificity 100%, accuracy 78%. At site level, sensitivity was significantly greater with FDG (p < 0.02) and specificity with FET (p < 0.01). The statistical level of significance was not reached at patient level. Conclusion  Although its good specificity was confirmed, FET did not appear to be suited as a first-line PET tracer in HNSCC imaging and cannot replace FDG for staging due to insufficient sensitivity. However, it was useful in a few selected cases to favor a wait and see attitude when a FDG+ FET− focus was discovered in patients referred for systematic FDG PET during follow-up. In contrast, second primary cancers should not be ruled out if FDG was clearly positive in the lungs or the digestive tract.     

Standardized Uptake Value Atlas: Characterization of Physiological 2-Deoxy-2-[<Superscript>18</Superscript>F]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose Uptake in Normal Tissues

Purpose The purpose of this study was to map the distribution of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) uptake in organs of patients with no known abnormalities in those tissues. Procedures We measured maximum and mean standardized uptake values (SUV) from FDG-positron emission tomography (PET)/computed tomography (CT) obtained from 98 patients (48 males and 50 females). Results Significant uptake (mean SUV_mean > 2.5) was visualized in the cerebellum (8.0 ± 2.2), soft palate (2.92 ± 0.86), palatine tonsils (3.45 ± 1.4), lingual tonsils (3.08 ± 1.05), sublingual glands (3.3 ± 1.5), and testes (2.57 ± 0.56). Negative correlation for FDG uptake versus age was observed for the palatine tonsils, sublingual glands, and lungs (P < 0.001). Conclusion Better understanding of physiological uptake throughout the body is valuable for improved interpretive accuracy and should be useful for future semi-automated comparisons to a normal SUV database.     

Performance of FDG PET/ceCT in the evaluation of patients with lung cancer

Aim

The aim of this study was to assess the performance of FDG PET/ceCT simultaneously acquired, contemporary read and finally discussed by the radiologist and the nuclear medicine physician for staging and restaging lung cancer patients.

Methods

We analysed 17 consecutive patients (7F; 10M; mean age 68). Six patients were in staging, 8 patients were in restaging (1 during therapy, 2 after therapy and 5 during the follow-up) and 2 patients needed to characterise a suspect pulmonary mass. All the patients underwent combined FDG PET/CT and ceCT acquired simultaneously on the same tomograph. The images were read and reported together by the nuclear medicine physician and the radiologist.

Results

None of the patients had adverse reactions nor complained about the procedure. Thirteen FDG PET/ceCT turned out positive, while 4 were completely negative. Among positive patients, a significant SUV max was detected in all the cases (range 1.8–17.5). In the end, 9 patients had a true positive result, 4 true negative, 3 false positive and 1 false negative. Sensitivity, specificity and accuracy of the combined procedure were 90%, 57% and 76% respectively. In 7/17 patients FDG PET/CT and ceCT were completely concordant. FDG PET/CT provided a significant impact on the final interpretation in 7/17 patients while ceCT had a major impact in 3/17 patients.

Discussion

This preliminary study shows that FDG PET/ceCT is a feasible technique for lung cancer patients, providing an optimal sensitivity (90%). From our results it is advisable not to include patients without an histological diagnosis of cancer due to possible false positivity of the two methods, significantly reducing specificity. However, a proper patient selection is not easy and the future of this combined test relies essentially on the capacity to early identify only the subjects who would really benefit from both the procedures.