Sensitivity Of Core Needle Biopsy Research Articles

Diagnostic accuracy and safety of nonsurgical biopsy for diagnosing pulmonary ground-glass opacities: a systematic review and meta-analysis.

Introduction Previous meta-analyses have explored the diagnostic accuracy and safety of computed tomography-guided percutaneous lung biopsy of ground-glass opacities (GGOs). However, no research has investigated the role of nonsurgical biopsies (including transbronchial approaches). Additionally, studies reporting the diagnostic accuracy of GGOs with different characteristics are scarce, with no quantitative assessment published to date. We performed a systematic review to explore the diagnostic accuracy and safety of nonsurgical biopsy for diagnosing GGOs, especially those with higher ground-glass component and smaller nodule sizes. Methods A thorough literature search of four databases was performed to compile studies evaluating both or either of the diagnostic accuracy and complications of nonsurgical biopsy for GGOs. A bivariate random-effects model and random-effect model were utilized for data synthesis. The methodological quality of the studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Nineteen eligible studies with a total of 1,379 biopsy-sampled lesions were analyzed, of which 1,124 were confirmed to be malignant. Nonsurgical biopsy reported a pooled sensitivity of 0.89, a specificity of 0.99, and negative predictive value (NPV) of 60.3%. The overall sensitivity, specificity, and NPV of nonsurgical biopsy for diagnosing GGOs according to GGO component were 0.90, 0.99, and 77.2% in pure GGOs; 0.87, 0.99, and 67.2% in GG-predominant lesions; and 0.89, 1.00 and 44.1% in solid-predominant lesions, respectively. Additionally, the diagnostic sensitivity was better in lesions ≥ 20 mm than in small lesions (0.95 vs 0.88). Factors that contributed to higher sensitivity were the use of coaxial needle system and CT fluoroscopy, but not the needle gauge. The summary sensitivity of core needle biopsy (CNB) was not significantly higher than fine needle aspiration (FNA) (0.92 vs 0.84; P = 0.42); however, we found an increased incidence of hemorrhage in CNB compared with FNA (60.9% vs 14.2%; P = 0.012). Conclusion Nonsurgical biopsy for diagnosing GGOs shows high sensitivity and specificity with an acceptably low risk of complications. However, negative biopsy results are unreliable in excluding malignancy, necessitating resampling or subsequent follow-up. The applicability of our study is limited due to significant heterogeneity, indirect comparisons, and the paucity of data on bronchoscopic approaches, restricting the generalizability of our findings to patients requiring transbronchial biopsies. Trial Registry: PROSPERO; No.: CRD42023429977; URL: www.crd.york.ac.uk/PROSPERO/).

Multiple core histopathologies for discriminative diagnosis of phyllodes pathology in breast

Background: Historical patient’s records were analyzed. Patients diagnosed with phyllodes tumors of the breast who received preoperative core needle biopsy and undergone breast surgery at a tertiary cancer centre in Patna, Bihar, India from January 2020 to December 2020. The resulting data allowed us to compare the accordance between core needle biopsy and final histopathology of phyllodes tumor of the breast patients and evaluate the accuracy of core needle biopsy in preoperative diagnosis. Methods: This is a retrospective study evaluated the case records of one hundred twenty (n=120) patients for core needle biopsy findings and subsequent histopathology reports post-surgery. Sensitivity and significance of core needle biopsy was determined for phyllodes tumor of the breast. Results: A total of one hundred twenty (n=120) patients’ data were analyzed. There were ninety (n=90) fibroadenoma and thirty (n=30) phyllodes tumor patients. Sensitivity of core needle biopsy for benign tumor was 64.2%, borderline 40% and a malignant phyllodes tumor was 100% respectively. Conclusions: Core needle biopsy provides a pathological basis for pre-operative diagnosis of phyllodes tumor, but it has a low accuracy and offers limited guidance for surgical decisions, if used alone. An integrated assessment using needle biopsies in combination with clinical data and imaging features is suggested as a reliable strategy to aid phyllodes tumor diagnosis and subsequent treatment.

Ultrasound Guided Core Needle Biopsy in The Diagnosis of Suspicious Breast Lesions: Radiologist’s perspectives

Background: Ultrasound guided core needle biopsy is becoming a gold standard in the work up of suspicious breast lesion. In Iraq, radiologists are not taking the lead in core needle biopsy performance. Objectives: To evaluate the radiologist performance of core needle biopsy highlighting the precession and accuracy of the procedure, the concordance of ultrasound and histopathology, and identifying challenges facing the radiologist during the procedure. Subjects and Methods: A prospective study involving a total of 50 patients with ultrasound (US) BIRADS IV or V. Ultrasound guided core needle biopsy was performed for each patient. Surgical pathology diagnosis was available for 40 patients. core needle biopsy results were correlated with Breast Imaging-Reporting and Data System (BI-RADS) categories and validity of the test was evaluated. Results: Malignancy was confirmed by histopathology in 76% of the cores. Concordance between BI-RADS(US) and histopathology for benignity and malignancy was achieved in all cores. Borderline lesions constituted 10% of total cores taken. Surgical resection of these lesions upgraded 3/5 (60%): two atypical ductal hyperplasia and an intraductal papillary lesions diagnosed by core needle biopsy found to be invasive ductal carcinoma after surgical resection. Sensitivity of core needle biopsy in this study was 91.4% with 100% specificity. Positive and negative predictive values were 100% and 62.5% respectively. The underestimation rate in high-risk group was 3/5 (60%). No significant complication was reported. Conclusion: Ultrasound guided core needle biopsy is a safe, efficient and relatively inexpensive method in diagnosing suspicious breast lesions. Radiologists can produce high sensitivity and specificity results. Radio pathological correlation is of paramount in achieving accurate results.

Core Needle Biopsy in the Diagnosis of Thyroid Nodules.

Core needle biopsy (CNB) is a relatively new technique for the diagnosis of thyroid nodules, and there are currently no large clinical series available. CNB results from 3000 cases are presented in this article. A spring-loaded 20-gauge needle was used for CNB under local anesthesia and ultrasonography guidance for 3000 patients with nodular goiter (584 males, 2416 females, mean age: 48.5). One physician performed all biopsy procedures without conducting on-site pathological examinations. There were non-diagnostic 22 (.7%), benign 2620 (87.4%), atypia of undetermined significance and/or, follicular lesion of undetermined significance 90 (3%), follicular neoplasms and/or suspicious for follicular neoplasm 53 (1.7%), suspicious for malignancy 160 (5.4%), and malignant 55 (1.8%) cases. The CNB procedure was repeated in 19 non-diagnostic cases, and 17 of these patients were benign and two had malignancy. Thyroidectomy was performed on patients who had malign CNB results. All final pathology reports, except for one, were malignant for the patients who had malignant CNB results. The specificity and the sensitivity of CNB were found to be 99.9% and 100%, respectively. There were no serious complications. In thyroid nodules, core needle biopsy is a highly sensitive, specific, and reliable method that could be performed by a single physician. It does not require on-site pathological analysis and has a low incidence of complications and non-diagnostic rates.

Supplementary benefits of CT-guided transthoracic lung aspiration biopsy for core needle biopsy.

ObjectiveThis study aimed to investigate the diagnostic efficacy of computed tomography (CT)-guided transthoracic lung core needle biopsy combined with aspiration biopsy and the clinical value of this combined routine microbial detection.Materials and methodsWe retrospectively collected the electronic medical records, CT images, pathology, and other data of 1085 patients with sequential core needle biopsy and aspiration biopsy of the same lung lesion under CT guidance in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to January 2021. GenXpert MTB/RIF detection and BD BACTEC™ Mycobacterium/fungus culture were applied to identifying the microbiological results of these patients. We then compared the positive diagnostic rate, false negative rate, and diagnostic sensitivity rate of three methods including core needle biopsy alone, aspiration biopsy alone, and both core needle biopsy and aspiration biopsy.ResultsThe pathological results of cutting histopathology and aspiration of cell wax were examined for 1085 patients. The diagnostic rates of cutting and aspiration pathology were 90.1% (978/1085) and 86.3% (937/1085), respectively, with no significant difference (P > 0.05). Considering both cutting and aspiration pathologies, the diagnostic rate was significantly improved, up to 98% (1063/1085) (P < 0.001). A total of 803 malignant lesions were finally diagnosed (803/1085, 74.0%). The false negative rate by cutting pathology was 11.8% (95/803), which was significantly lower than that by aspiration biopsy [31.1% (250/803), P < 0.001]. Compared with core needle biopsy alone, the false negative rate of malignant lesions decreased to 5.6% (45/803) (P < 0.05). Next, the aspirates of the malignant lesions highly suspected of corresponding infection were cultured. The results showed that 16 cases (3.1%, 16/511) were infected with Mycobacterium tuberculosis complex, Aspergillus niger, and Acinetobacter baumannii, which required clinical treatment. 803 malignant tumors were excluded and 282 cases of benign lesions were diagnosed, including 232 cases of infectious lesions (82.3%, 232/282). The diagnostic rate of Mycobacterium/fungus culture for infectious lesions by aspiration biopsy (47.4%) was significantly higher than that by lung core needle biopsy (22.8%; P < 0.001). The diagnostic rate of aspiration biopsy combined with core needle biopsy was 56% (130/232). The parallel diagnostic rate of aspirated biopsy for GenXpert detection and Mycobacterium/fungal culture combined with core needle biopsy was 64.7% (150/232), which was significantly higher than that of lung core needle biopsy alone (P < 0.001). Finally, pulmonary tuberculosis was diagnosed in 90 cases (38.8%) of infectious lesions. Compared with the sensitivity of core needle biopsy to detect tuberculosis (27.8%, 25/90), the sensitivity of aspirating biopsy for GenXpert detection and Mycobacterium/fungal culture was significantly higher, at 70% (63/90) and 56.7% (51/90), respectively. Although there was no significant difference in the sensitivity of aspirated biopsy for GenXpert and Mycobacterium/fungal culture to detect pulmonary tuberculosis, the sensitivity was significantly increased to 83.3% (P < 0.05) when the two tests were combined. Moreover, when aspirated biopsies were combined with GenXpert detection, Mycobacterium/fungus culture, and core needle biopsy, the sensitivity was as high as 90% (81/90).ConclusionCT-guided lung aspiration biopsy has a significant supplementary effect on core needle biopsies, which is indispensable in clinical application. Additionally, the combination of aspiration biopsy and core needle biopsy can significantly improve the diagnostic rate of benign and malignant lesions. Aspiration biopsy showed that pulmonary malignant lesions are complicated with pulmonary tuberculosis, aspergillus, and other infections. Finally, the diagnostic ability of lung puncture core needle biopsy and aspiration biopsy combined with routine microbial detection under CT positioning in the diagnosis of pulmonary infectious diseases was significantly improved.

Comparative Study of Tru-Cut Biopsy and FNAC in A Clinically Palpable Breast Lump

Background &amp; Objective: Fine-needle aspiration cytology (FNAC) is frequently used to evaluate a breast lump, for it is safe, reliable, and time saving outdoor procedure for evaluation of breast lumps. However, in recent times, the diagnosis of breast lesions has mostly become dependent on Tru-cut biopsies with a gradual reduction in the rate of performing fine-needle aspiration cytology (FNAC). The present study was undertaken to compare the diagnostic accuracy of Tru-cut Biopsy and Fine Needle Aspiration Cytology (FNAC) in the evaluation of a clinically palpable breast lump.&#x0D; Methods: This cross-sectional study was conducted in the in Department of Surgery, Rajshahi Medical College &amp; Hospital, Rajshahi, Bangladesh over a period of one year from July 2019 to June 2020. A total of 60 women with clinically palpable breast lumps were consecutively included in the study. All patients underwent FNAC and Tru-cut Biopsy to make a provisional (clinical) diagnosis of breast lump followed by histopathology of the excision biopsy taken during surgery to confirm the diagnosis. The diagnostic accuracies (sensitivity, specificity, positive and negative predictive values) of the two diagnostic modalities (FNAC and Tr-cut Biopsy) were then judged by comparing them with the histopathological diagnosis of the excision biopsy.&#x0D; Result: In the present study majority (86.7%) of the lesions was malignant in terms of histopathology with almost all being infiltrating carcinoma (98%). Only 8(13.3%) cases were benign breast lesions and all of them were fibroadenoma. While Tru-cut or Core-needle biopsy (CNB) diagnosed 85% of the lesions as malignant, FNAC diagnosed 65% of lesions as malignant. The sensitivity of CNB was observed to be 98.1% and its specificity was 100%. In contrast, the sensitivity of FNAC was much lower (65%), although its specificity was comparable to that of CNB (100%). While the overall diagnostic accuracy of CNB was 98.3%, that of FNAC was 78.3%. The test of agreement between Tru-cut biopsy and FNAC using kappa-statistics showed that the two diagnostic modalities had moderate agreement in differentiating malignant breast tumours from the benign ones (k-value = 0.494, p &lt; 0.001).&#x0D; Conclusion: The study concluded that Tru-cut biopsy and FNAC both are hundred percent specific in excluding a benign breast lesion. However, the sensitivity of FNAC is much lower compared to that of CNB with overall diagnostic accuracy of Tru-cut biopsy being much higher than FNAC.&#x0D; Ibrahim Card Med J 2021; 11 (1): 21-27

Core needle biopsy is an inferior tool for diagnosing cervical lymphoma compared to lymph node excision

Background In Denmark, fine needle aspiration is the standardized tool for obtaining tissue samples from lymph nodes (LN) of the neck. However, because of a low specificity toward lymphomas, LNs suspicious for this disease are often surgically removed and examined. International studies have implied that a core needle biopsy (CNB) is sufficient for detecting lymphomas, thereby potentially avoiding surgery. However, all studies have been conducted retrospectively and the goal of this prospective study was to find the true sensitivity of CNB. Material and Methods Fifty-seven patients were enrolled in the study, one was excluded due to lack of CNB material. LNs suspected for lymphoma were surgically removed from the neck, whereafter a CNB was obtained from the removed LN. The CNB and the remaining part of the LN were sent to the Department of Pathology for further processing and the samples were blinded and examined by two pathologists separately. A consensus diagnosis was reached in cases with divergent diagnostic proposals. Sensitivity of the CNB method in comparison to whole tissue sections for lymphoma diagnosis was calculated. Results The CNB method gave the correct diagnosis in 66% of lymphoma cases, was inconclusive in 14% and gave an incorrect lymphoma subtype in 18%. In 2% the CNB wrongly resulted in a benign diagnosis. CNB was correct in all the non-lymphoma cases; thereby retaining a specificity of 100%. Conclusion This prospective study found a sensitivity of 66% for diagnosing lymphoma with a CNB. As the CNB in this study was obtained under optimal conditions, unlike in clinical practice, we conclude that CNB cannot be recommended as a standard tool for diagnosing lymphomas.

Pre-operative Axillary Ultrasound-Guided Needle Sampling in Breast Cancer: Comparing the Sensitivity of Fine Needle Aspiration Cytology and Core Needle Biopsy

Pre-operative ultrasound-guided needle sampling (UNS) of abnormal axillary lymph nodes in breast cancer can identify patients with axillary metastases and therefore rationalize patient care and inform decision-making. To obtain tissue diagnosis, UNS can be performed by either fine needle aspiration (FNA) or core needle biopsy (CNB). However, few studies have compared the sensitivity of these techniques and the majority show no difference. All node-positive patients (those with micro- and macrometastases but not isolated tumor cells) treated at a tertiary referral center between January 2012 and December 2015 were retrospectively identified from pathology records. The result of the first axillary UNS performed on each patient was compared with postoperative histopathology results. The UNS method used was according to individual radiologist preference. A total of 215 patients underwent FNA (1 patient had bilateral breast cancer and underwent bilateral FNA), and 92 underwent CNB. Sensitivity of CNB was significantly higher than FNA (83.7 vs. 69.0%, P=0.008). The false-negative rate in the FNA group was therefore higher than in the CNB group by a factor of 2.5. There was no difference in inadequacy rate between the two techniques. There were no complications in the FNA group, and only one hematoma (which did not require operative intervention) in the CNB group. CNB is safe and should be the preferred technique for UNS to improve sensitivity.

The Role of Core Needle Biopsy for Thyroid Nodules with Initially Indeterminate Results on Previous Fine-Needle Aspiration: A Systematic Review and Meta-Analysis.

Sonography-guided fine-needle aspiration leads to relatively frequent cases of indeterminate cytology for the diagnosis of thyroid nodules. Our aim was to evaluate the efficacy and safety of core needle biopsy for the examination of thyroid nodules with initially indeterminate results on fine-needle aspiration. A computerized search of the MEDLINE and Embase databases was performed to identify relevant original articles. Studies investigating the use of core needle biopsy for thyroid nodules with initially indeterminate results on previous fine-needle aspiration were eligible for inclusion. The pooled proportions for nondiagnostic results, inconclusive results, malignancy on core needle biopsy, the ability of core needle biopsy to diagnose malignancy, and the related complications of the procedure were analyzed. The meta-analytic pooling was based on a random-effects model. Nine eligible studies, involving 2240 patients with 2245 thyroid nodules, were included. The pooled proportion for nondiagnostic results was 1.8% (95% CI, 0.4%-3.2%), and the pooled proportion for inconclusive results was 25.1% (95% CI, 15.4%-34.9%). The pooled proportion for malignancy was 18.9% (95% CI, 8.4%-29.5%). With regard to the diagnostic performance for malignancy, the sensitivity of core needle biopsy varied, ranging from 44.7% to 85.0%, but the specificity was 100% in all cases. No major complications of core needle biopsy were observed. The relatively small number of included studies and retrospective nature were limitations. Core needle biopsy has low nondiagnostic result rates and high specificity for the diagnosis of malignancy. It is a safe diagnostic technique with a higher diagnostic yield, especially when molecular testing is not available or fine-needle aspiration did not yield enough cells for molecular testing.

Diagnostic performance of core needle biopsy in identifying breast phyllodes tumors.

A retrospective analysis of diagnoses was performed in patients with phyllodes tumors of the breast (PTB) who received preoperative core needle biopsy (CNB) and had breast surgery at Fudan University Shanghai Cancer Center from January 1, 2002 to April 1, 2013. The resulting data allowed us to compare the accordance between CNB and excision diagnoses of PTB patients and evaluate the accuracy of CNB in preoperative diagnosis. Data from 128 patients with PTB who had undergone preoperative CNB and breast surgery were retrospectively analyzed. We reviewed the medical history, clinical follow-up data, and CNB diagnostic data. A diagnostic test was used to evaluate the sensitivity and specificity of CNB in diagnosing benign, borderline, and malignant phyllodes tumors. The accuracy of CNB for diagnosing PTB was 13.3% (17/128). Of the remaining patients, 98 (75.5% of the PTB patients) were diagnosed with fibroadenoma or fibroepithelial lesions. The sensitivity of CNB at diagnosing benign, borderline, and malignant phyllodes tumors were 4.9% (2/41), 4.2% (3/71), and 25.0% (4/16), respectively, whereas the corresponding specificity were 92.0%, 98.2%, and 100%, respectively. Some clinical features, such as large tumor size, rapid growth, or surgical history of fibroadenomas, were indicative of an increased possibility of PTB. CNB provides a pathological basis for the preoperative diagnosis of PTB, but it has a poor accuracy and offers limited guidance for surgical decisions. Considering CNB along with multiple histologic features may improve the ability to accurately diagnose PTB. An integrated assessment using CNBs in combination with clinical data and imaging features is suggested as a reliable strategy to assist PTB diagnosis.

Predicting the biologic classification of phyllodes tumors from preoperative core needle biopsy and imaging findings.

86 Background: Phyllodes tumors (PT) are rare breast neoplasms confounding their systematic study and evidence-based management guidelines. There is little data on the sensitivity of preoperative core needle biopsy (CNB) and imaging findings in establishing a correct preoperative diagnosis. We undertook this study to evaluate the sensitivity of CNB histologic findings and imaging findings in preoperatively categorizing tumors as benign or borderline/malignant. Methods: We identified 47 patients who underwent surgical resection of a PT at our institution after a preoperative CNB between 6/2000-3/2012. Statistical analysis utilized Wilcoxon rank-sum, chi-square or Fisher’s exact tests, and 95% confidence intervals (CI) are reported. Results: 30 patients had a final diagnosis of benign and 17 of borderline/malignant PT. The latter were significantly more often palpable (76.5% vs 36.7%, p=0.01). No other clinical or radiologic feature predicted borderline/malignant subtype, although irregular shape on US was suggestive (70.6% vs 44.8%, p= 0.09). CNB diagnosis by tumor type is summarized in the table. No benign PT had ≥10 mitoses, necrosis or marked stromal atypia on CNB. No case with absent mitoses on preoperative CNB was a borderline/malignant PT; however 77% of benign PT did exhibit mitoses on CNB. Sensitivity of CNB for PT overall was 48.9% (95% CI: 35.3-62.8%) while it was 40% (24.6-57.7%) for benign PT and 17.6% (6.2-41.0%) for borderline/malignant PT. Conclusions: Marked stromal atypia, ≥10 mitoses and necrosis were rare on CNB, but suggestive of malignancy. No imaging or histology feature reliably distinguished between tumor types. Over one-third of borderline/malignant PT had a preoperative CNB diagnosis of fibroadenoma or cellular fibroepithelial lesion emphasizing the low sensitivity of CNB and the need for judicious consideration of definitive surgical excision. [Table: see text]

Diagnostic role of core needle biopsy in cervical lymphadenopathy

The purpose of this study was to evaluate the value of core needle biopsy (CNB) compared to fine-needle aspiration cytology (FNAC) in cervical lymphadenopathy. This consecutive case series enrolled 208 patients with cervical lymphadenopathy. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated and the necessity of an additional open biopsy was compared. The sensitivity and NPV for critical disease (lymphoma, carcinoma, and tuberculosis) were significantly higher with CNB (p = .006, p = .001, respectively) than with FNAC. In the analysis based on specific disease, the sensitivity of CNB was statistically significantly higher (p = .009) for the diagnosis of lymphoma. The rate of open biopsy for confirmative diagnosis was significantly lower with CNB (p = .014). CNB is beneficial for initial examination in cervical lymphadenopathy and showed higher sensitivity and NPV than FNAC. It is especially useful for screening for lymphoma.

A Comparison of Different Imaging Techniques for Localisation of Cancers in the Prostate

The diagnostic accuracy of standard transrectal ultrasound-guided (TRUL) biopsy is limited due to the finite number of cores that can be obtained. It has been shown that the technique is not sufficiently reliable in defining the location and extent of prostatic cancer. The main aim of this study was to investigate the effectiveness of magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) imaging techniques in pinpointing potential tumour lesions prior to prostate biopsy.Material and methodsThe study cohort consisted of 45 men with a raised prostate specific-antigen (PSA) level and/or suspected prostate cancer (PCa) at digital rectal examinations (DRE). Of the 45 patients, 23 had PCa detected with core needle biopsy (CNB). All had 11C acetate PET/CT imaging. Ten of those 23 patients underwent radical prostatectomy (RP), of those ten patients, eight patients had MR spectroscopic imaging (MRSI) with 3 T and six had diffusion weighted imaging (DWI) with apparent diffusion coefficient calculation (MRI DWI ADC). CNB, PET/CT, 2D MRSI and ADC map results were compared with postoperative specimen histopathology.Results The sensitivity of CNB, PET/CT, MRSI and DWI ADC were 0.53, 0.55, 0.79 and 0.95, whereas the specificity of was 0.88, 0.87, 0.46 and 0.73, respectively.Conclusion MRI improves the PCa detection by defining the areas of interest for targeted CNB of the prostate and can reduce the number of biopsies required

A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Ultrasound-Guided Core Needle Biopsy for Salivary Gland Lesions

Core needle biopsy (CNB) of salivary gland lesions is a relatively new technique that may offer benefits for diagnosis of the lesions. We conducted a systematic literature review to identify studies published between January 1, 1985, and March 15, 2011. Summary estimates of sensitivity and specificity were obtained by using a summary receiver-operating characteristic (SROC) curve. Study quality was assessed by using the QUADAS survey. We identified 5 studies (277 cases) for inclusion. The area under the SROC for CNB was 1.00 (95% confidence interval [CI], 0.99-1.00). Based on histologically verified cases, the sensitivity of CNB is 0.92 (95% CI, 0.77-0.98) and the specificity is 1.00 (95% CI, 0.76-1.00). We conclude that CNB has high accuracy and a low (1.2%) inadequacy rate. CNB is more accurate than fine-needle aspiration, at least in some settings, but the best selection of which test to use for an individual patient and setting remains to be defined.