Core Biopsy Specimens Research Articles

Abstract OT3-20-03: Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796

Abstract Introduction The aim of the study was to prove efficacy and safety of de-escalation of traditional breast surgery in BC patients who develop cCR after neoadjuvant systemic therapy. Refusal of surgery was offered to exceptional responders after vacuum-assisted tumor bed biopsy and sentinel lymph node biopsy confirmed absence of residual disease (pCR). Materials and methods A single-center prospective study was run in the NMRC n.a. N.N. Petrov. Starting from August of 2020, 35 patients with early сT1-2N0-1M0 (stage Ia-IIb) triple-negative and HER2-positive (both ER+ and ER-) unifocal tumours without DCIS in core-biopsy specimen enrolled in the study. Primary lesions were marked with a single clip in the centre. In cases with nodal involvement (cN1) the affected lymph nodes were also clipped. Patients with triple-negative breast cancer received 4 cycles of AC q21d followed by 12 cycles of weekly paclitaxel and carboplatin AUC 2.0. HER2-positive patients received 4 cycles of AC followed by 4 cycles of docetaxel combined with trastuzumab and pertuzumab q21d. Breast US, mammography and SPECT were used at baseline and at response evaluation. Vacuum-assisted biopsy was performed with 7G needle and US-guidance in the OR simultaneously with the SLNB. VAB protocol included retrieval of the tumor clip as first stage. Subsequently surrounding tissues were sampled, and markers were placed to guide radiotherapy. In case residual tumor was found patients received standard breast-conserving surgery. In case the sentinel lymph nodes were found to be positive, standard level II axillary clearance was performed. HER2-positive patients with pCR confirmed by VAB and SLNB received adjuvant trastuzumab up to one year. HER2-positive patients with residual breast or nodal involvement received trastuzumab emtansine up to one year. In case ER+, all patients received appropriate endocrine-therapy. In case of residual in-breast or nodal involvement patients with triple-negative breast cancer received standart capecitabine. Results The interim analysis included 25 patients in both groups. The median follow-up of disease-free survival for patients is 12 months. In the triple-negative group 12 patients achieved cCR. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 11 patients (91.7%). 1 patient had invasive residual tumor with less than 5% cellularity. FNR in this group was 8.3% (1/12). Patient with invasive residual tumor received standard breast-conserving surgery. All the patients in the TNBC group were also found to be (sn)ypN0. In the HER2-positive group cCR was achieved 13 patients. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 10 patients (77%). 3 patients had invasive residual tumor with less than 5% cellularity. FNR in this group was 23% (3/13). Patients with invasive residual tumor received standard breast-conserving surgery. All HER2-positive patients were found to be (sn)ypN0. One patient with HER2-positive subtype experienced a local reccurence in the postoperative zone 16 months after surgery. Initially, this patient achieved cCR and undergone VAB with SLNB. On final pathomorphologic examination isolated focuses of DCIS were found (ypTisN0). Standard breast-conserving surgery was performed and histologically only DCIS was found. This patient recieved 1-year of Trastuzumab and standard radiotherapy with boost. After the histologic confirmation of local reccurence patient underwent nipple-sparring mastectomy with reconstruction and nowadays she is recieveing therapy with trastuzumab emtansine (T-DM1). Conclusion All visualization modalities fail to provide reliable information on the true rate of pCR. Contemporary systemic therapy regimens after accurate selection of patients, following the inclusion criteria, allows to achieve pCR in 75-90%, thereby reducing the risk of FNR after VAB. The trial continues to enroll patients and further follow-up is needed. Citation Format: Petr Krivorotko, Sergey Yerechshenko, Alexander Emelyanov, Ekaterina Busko, Tengiz Tabagua, Viktoria Mortada, Konstantin Zernov, Alexander Komyakhov, Kirill Nikolaev, Elena Zhiltsova, Larisa Gigolaeva, Roman Pesotsky, Diana Enaldieva, Yana Bondarchuk, Nikolay Amirov, Valentin Channov, Sergey Novikov, Zhanna Bryantseva, Anna Artemyeva, Viktoriya Smirnova, Tatiana Semiglazova, Alexey Belyaev, Vladimir Semiglazov. Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-03.

Unchartered waters: Significance of fall in Ki67 index after short-term preoperative endocrine therapy in early breast cancers.

Endocrine treatment for breast cancer acts largely by inhibiting tumor cell proliferation. The biomarker Ki67 is linked to the proliferative index of the tumour. To identify the factors affecting the fall in Ki67 value in early-stage hormone receptor (HR) positive breast cancer patients receiving short-term preoperative endocrine therapy in an Indian cohort. Women with hormone receptor positive, invasive, nonmetastatic, and early breast cancer (<T2, <N1) were assigned to short-term preoperative tamoxifen 20 mg daily (pre-menopausal women) or Letrozole 2.5 mg daily (post-menopausal women) for a minimum of 7 days after noting the baseline Ki67 value from the diagnostic core biopsy specimen. The postoperative Ki67 value was estimated from the surgical specimen, and the factors determining the extent of fall were evaluated. The short-term preoperative endocrine therapy resulted in a reduction in the median Ki67 index, which was significantly greater among postmenopausal women who received Letrozole (63.25 (31.94-80.5)) than among premenopausal women who received Tamoxifen (0 (-28.99-62.25)) (p-value 0.001). The fall in Ki67 value was particularly marked for patients with low-grade tumors with high Estrogen and progesterone receptor expression (p-value < 0.05). The duration of treatment (<2 week or 2-4 week or >4 week) did not affect the fall in Ki67. Preoperative therapy with Letrozole resulted in a more significant fall in Ki67, as compared to therapy with Tamoxifen. Determining the fall in Ki67 value in response to preoperative endocrine therapy could provide an insight into the response to endocrine therapy in luminal breast cancer.

Invasive urothelial carcinoma with squamous differentiation and associated high-risk human papilloma virus infection: Clinical, cytologic, and histologic features of a rare entity

We correlate the fine needle aspiration (FNA) cytologic findings with the histologic features of an invasive high-grade urothelial carcinoma showing squamous differentiation in the setting of high-risk Human Papilloma Virus (hrHPV) infection. To our knowledge, only extensive urinary bladder catheterization has been associated with hrHPV-positive urothelial carcinoma with squamous differentiation, and rarely at that. Herein, we present a case arising in a patient with only sparse and intermittent catheterization. A 69-year-old woman presented with voiding difficulties, and after continued symptoms, a Foley catheter was placed, and a cystoscopy procedure revealed two 1–2 cm inflammatory masses. Excisional biopsies were interpreted as papillary urothelial carcinoma. One month follow-up pelvic imaging demonstrated a new mass involving the urinary bladder neck, with irregular wall thickening and perivesical fat stranding, as well as probable vaginal involvement. CT-guided FNA (CT-FNA) to collect smears and core biopsies revealed an invasive urothelial carcinoma with squamous differentiation. HPV-cytopathic changes amid squamous metaplasia and dysplasia were noted on FNA smears with HPV E6/E7 RNA in situ hybridization (ISH) showing on the FNA core biopsy specimen. Immunostains showed that the tumor cells were positive for P16 (strong, diffuse), CK7, p63, ER, and GATA3 (patchy). Subsequent radical cystectomy revealed the extent of the patient's carcinoma, with direct extension to the vaginal wall, and involvement of the radial soft tissue resection margins. Describing the cytomorphologic features of a hrHPV positive urothelial carcinoma with squamous differentiation, without an extensive history of urinary catheterization or prior known history of HPV infection, emphasizes the role of cytopathology as a powerful diagnostic tool for recognizing a unique and unexpected lesion.

Association of CD10 and VEGF Expression with Tumour Characteristics and Treatment Response in Patients of Carcinoma BreastA Prospective Cohort Study

Introduction: Majority of breast cancer patients receive systemic therapy. This has led to an extensive search for effective factors to predict the outcome. Two such markers for breast cancer are Cluster of Differentiation 10 (CD10) and Vascular Endothelial Growth Factor (VEGF). There is limited data available in the literature to support these parameters in breast cancer patients, especially from the Indian subcontinent. Aim: To ascertain the association of pre-chemotherapy levels of CD10 and VEGF with tumour load in breast cancer and treatment response. Materials and Methods: A prospective cohort study was conducted in the Department of Surgery in collaboration with the Department of Pathology at Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, India, from November 2015 to February 2017. A total of 39 patients with Locally Advanced Breast Cancer (LABC) were included in the study. Preoperative levels of CD10 and VEGF were estimated in large needle core biopsy specimens. Standard anthracycline based chemotherapy was given to all patients as a 21 days cycle for three cycles. All patients underwent modified radical mastectomy after Neoadjuvant Chemotherapy (NACT). Levels of CD10 and VEGF were estimated again in the mastectomy specimen. Increase/decrease or no change in VEGF and CD10 expression percentage was ascertained for each patient after systemic therapy. Variables that were studied in the present study were Tumour, Nodes, and Metastasis (TNM) staging of patient, expression of VEGF and CD10 in large needle core biopsy specimens and its association with tumour load, response to NACT and its association with CD10 and VEGF and histopathological characteristics like presence or absence of lymphovascular invasion oestrogen, progesterone and Human Epidermal Growth factor Receptor 2 (HER2)/neu receptor status. Statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 22.0. Association between two ordinal variables was established using Kruskal-Wallis test. A comparison of ordinal paired data was done using Wilcoxon signed-rank sum test. The p-value &lt;0.05 was taken as significant. Results: The mean age of study participants was 42.0±11.4 years. Increase in TNM staging lead to higher CD10 and VEGF expression (p-value&lt;0.05 and &lt;0.029, respectively). There was a significant reduction in CD10 and VEGF expression postchemotherapy (p-value&lt;0.05). CD10 expression was found higher in subjects with ER-negative status (22 patients) with p-value=0.014 and HER2/neu positive status (19 patients) with p-value=0.028. Subjects with HER2/neu positive status had higher VEGF expression (20 patients) with p-value=0.032. Conclusion: CD10 and VEGF can be used as independent markers for indicating poor prognosis and can be used as target for development of novel therapies in carcinoma breast.

Upgrade Rate and Predictive Factors Associated With Breast Papillary Lesions on Core Biopsy: A Canadian Experience.

Background: Papillary lesions of the breast are a heterogeneous group, encompassing a wide range of lesions. The histologic distinction between papillary breast lesions remains challenging, especially on core biopsy specimens. Aim: This study aimed to determine the rate of upgrade to atypia or malignancy of biopsy-proven papillary lesions on surgical follow-up and to assess for factors associated with an upgrade in Greater Vancouver, BC, Canada. Materials and Methods: This is a retrospective population-based study of all breast papillary lesions diagnosed on core biopsy between 2017 and 2019 in the Fraser Health Authority in Greater Vancouver, Canada. Patients were retrieved from the laboratory information system. Patient demographics, histopathologic, and radiologic findings were analyzed. Results: A total of 269 specimens from 269 patients (mean 61.1 years), including 265 female and 4 male patients, were included in the study. Of the 269 specimens, 129 (48%) were intraductal papillomas and 140 (52%) were atypical papillary lesions. The overall upgrade rate among papillomas was 11.6% (15 of 129) on final excision. The mean age of patients diagnosed with papilloma on core biopsy was significantly younger than those with atypical papillary lesions (55.6 vs 66.1 years, P < .0001). Lesion size in patients with papillomas on core biopsy was significantly smaller than those with atypical papillary lesions (11.1 vs 15.1 mm, P = .001). The upgrade rates in patients <55 and ≥55 years were 4.9% and 13.2%. Size (P = .004) and atypia on core biopsy (P = .009) were significantly associated with upgrade. Older age (>55 years) (OR = 5.3, 95% CI: 1.04-27.08) was an independent predictor of upgrade among papillomas. Size, location, and Breast Imaging-Reporting and Data System (BI-RADS) radiologic categories in our study were not associated with predicting the upgrade of papillomas. Conclusion: Our data suggest that the risk of upgrade to atypia or malignancy is sufficient to warrant the excision of benign papillomas of any size in patients aged ≥55 years. In patients younger than 55 years, observation with close clinical and radiological follow-up without surgery may be sufficient. Our findings also support surgical excision of papillomas diagnosed on core biopsy when associated with atypia.

FNA 2.0: Value of cytopathologist-performed ultrasound-guided core-needle biopsy.

In the late 20th century, pathologist-performed palpation-guided fine-needle aspiration (PG-FNA) of superficial masses was popularized in the United States. It brought pathologists out of the laboratory to see patients and the hope of decreasing the need for surgical biopsy for diagnostic purposes. This first iteration of minimally invasive tissue sampling could be informally called FNA 1.0. FNA 1.0 had shortcomings, such as detection of invasion in breast cancer, precise subtyping of lymphomas, aspiration of fibrous lesions, and diagnosis of sarcomas. The early 21st century brought new hope. Ultrasound-guidance became commonly used to guide FNA of both palpable and non-palpable masses. Ultrasound-guided core-needle biopsy was available to complement FNA in select cases. Flow cytometry, immunohistochemistry, fluorescent in-situ hybridization, and genomic studies could be done on cell block and core biopsy specimens. These advances in minimally invasive tissue diagnosis could be informally called FNA 2.0. In particular, pathologist-performed ultrasound-guided core-needle biopsy can overcome many of the criticisms and shortcomings of FNA. As pathologists were once leaders in palpation-guided fine-needle aspiration, they now have the opportunity to add pathologist-performed ultrasound-guided core-needle biopsy to their skill set and emerge once again as leaders in minimally invasive tissue diagnosis. This will bring pathology to the next level.

Indeterminate (B3) breast lesions: experience with vacuum-assisted biopsy under ultrasound guidance

INTRODUCTION: Introduction of breast cancer screening programs has led to an increase in detection of non-palpable masses requiring core needle biopsy. Masses that fall into B3 category based on the histological results of core biopsy specimens, are of interest precisely because of their uncertain malignant potential and the lack of a final consensus on their management.OBJECTIVE: To analyze the 3-year experience of ultrasound guided vacuum-assisted biopsy (VAB) in patients with B3 breast lesions based on the results of histological examination of core biopsy specimens.MATERIALS AND METHODS: Between June 2019 and June 2022, 163 VABs were performed. The study group included patients with category 2–4 breast lesions according to the BI-RADS scoring system. The decision to perform VAB was made by the oncologist in each specific case on the basis of anamnesis, clinical data and the results of core biopsy histological examination: in cases of B3 or B2 lesions with a discordant radiologic pattern.RESULTS: In 155 (95.0%) cases, the removed lesions were benign, invasive cancer was detected in 2 (1.2%) cases, ductal cancer in situ in 6 cases (3.8%). The сomplications included: in 5 (3.1%) cases, patients had pain after the procedure, and in 37 (22.7%) cases there was a hematoma. In 5 (3.1%) patients, residual tissue was found at the site of removed lesions. CONCLUSIONS: VAB is a safe alternative to exploratory surgery in patients with B3 lesions diagnosed by core biopsy.

Use of Real Time Specimen Radiography to Evaluate the Number of Stereotactic Core Biopsy Specimens Containing Calcifications Required for Diagnosis.

To determine the minimum number of stereotactic biopsy specimens containing calcifications sufficient for pathologic diagnosis and the minimum number of specimens containing calcifications sufficient for immunohistochemistry (IHC) in cases of malignancy. In this IRB-exempt quality assurance initiative, individual specimens from 126 patients with 129 calcified targets retrieved using a stereotactic system with real time specimen imaging were prospectively analyzed. Pathology was reported independently for each specimen containing calcifications. In every case, the pathologist reported which specimen containing calcifications was sufficient for diagnosis and, in cases of malignancy, which calcified specimen was sufficient for diagnosis and IHC. A diagnosis was made from the first calcified specimen in 74% of cases (95/129), from the first two calcified specimens in 92% (119/129) of cases, and from the first three calcified specimens in 100% of cases. Pathology was benign in 66% (85/129) of cases, with the diagnosis made from the first calcified specimen in 78% (66/85) of cases. High-risk lesions were the primary pathology in 8% (11/129) of cases, with 55% (6/11) diagnosed from the first calcified specimen. Pathology was malignant in 26% (33/129) of cases. The first calcified specimen was sufficient for diagnosis and IHC in 73% (24/33) of malignancies and the first three calcified specimens were sufficient for diagnosis and IHC in all cases of malignancy. Three cores verified to contain calcifications on real time specimen imaging were sufficient to make a diagnosis in all cases and to make a diagnosis and obtain IHC in nearly all cases of malignancy.

Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

AbstractKi67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

GRANULOMATOUS REACTION TO A MEDIASTINAL SEMINOMA

GRANULOMATOUS REACTION TO A MEDIASTINAL SEMINOMA

Algorithm-Based Approach to the Histological Routine Diagnosis of Renal Oncocytic Tumors in Core Biopsy Specimens.

A growing number of tumor entities with badly defined limits are enlarging in the last years the family of oncocytic tumors in the kidney. Chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO) are classically well-known tumors, but the borderland between them, and their precise connection, remains a matter of debate. Aside from that, other emerging and provisional entities, like eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumor (EVT), low-grade oncocytic tumor (LOT), and papillary renal neoplasm with reverse polarity (PRRP), have been recently described. This spectrum of tumors remains a diagnostic challenge in renal pathology, especially if the specimen obtained is scarce. This review focuses on practical diagnostic problems when managing core biopsies and proposes a diagnostic algorithm maximizing the information provided by both morphology and immunohistochemistry. So, a combination of morphologic features on hematoxylin-eosin and six antibodies (CK7, CD117, CK20, CD10, GATA-3, and cathepsin K) is advised to be used in a stepwise fashion.

IgG and IgM Immunohistochemistry in Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) Liver Explants.

Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) can be difficult to distinguish in end-stage liver disease. Previous studies have shown that immunoglobulin G (IgG) and immunoglobulin M (IgM) immunostaining can differentiate AIH from PBC in needle core biopsy specimens, and we seek to extend these data to cirrhotic liver explants, in which the histology of AIH or PBC may be indiscernible. Clinical data were reviewed for 20 patients with PBC cirrhosis and 16 with AIH cirrhosis. Immunohistochemistry for IgM and IgG was performed on representative blocks of explanted livers. Three high-power fields with the highest concentration of IgG- and IgM-positive plasma cells were counted and compared. The average number of IgM-positive plasma cells was significantly higher in PBC explants (7.3) than in AIH (1.8) (P = .001). There was no significant difference in the average number of IgG-positive plasma cells in PBC (2.5) and AIH (2.8) (P = .8). The IgG/IgM ratio was more likely to be less than 1.0 in PBC (17/20, 85%) compared with AIH (7/16, 44%) (P = .01). Our study demonstrates that the absolute number of IgM plasma cells is greater in explants of cirrhotic PBC compared with AIH. These findings may be helpful in the evaluation of cryptogenic cirrhosis.

Histopathological Correlation of Breast Carcinoma with Breast Imaging-Reporting and Data System.

BackgroundBreast cancer is one of the commonest malignancy cancer worldwide and the Breast Imaging-Reporting and Data System (BI-RADS) classification has been extensively utilised as an adjunct to histopathological examination for malignant breast diseases. This study aims to analyse the concordance between radiological and histopathological findings, demonstrate the high predictive value in the BI-RADS category and evaluate the impact of these findings on surgical intervention and treatment outcome.MethodsThis is a single-centre retrospective study, analysing patients who underwent radiological examination with BI-RADS categories 3, 4 and 5 followed by histopathological examination confirming the diagnosis based on breast core biopsy or excision specimen over 3 years.ResultsA total of 316 specimens from 310 patients were included in this study; 75 cases were categorised BI-RADS 3, 166 as BI-RADS 4 and 75 as BI-RADS 5. Of these, 66 (20.8%) patients in BI-RADS category 3, 82 (25.9%) in BI-RADS category 4 and 5 (1.6%) in BI-RADS category 5 were reported as benign on histopathological examination. Malignant cases were reported in nine (2.8%) cases in BI-RADS category 3, 84 (26.6%) in BI-RADS category 4 and 70 (22.2%) in BI-RADS category 5. The positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were 63.9%, 88%, 94.48%, and 43.14%, respectively.ConclusionThere is a significant correlation between BI-RADS score and histopathological results of breast cancer. A higher BI-RADS score is associated with a higher possibility of malignancy (P < 0.001). Our institution’s performance is comparable to other previously published data.

Potential quality pitfalls of digitalized whole slide image of breast pathology in routine practice

AbstractUsing digitalized whole slide images (WSI) in routine histopathology practice is a revolutionary technology. This study aims to assess the clinical impacts of WSI quality and representation of the corresponding glass slides. 40,160 breast WSIs were examined and compared with their corresponding glass slides. The presence, frequency, location, tissue type, and the clinical impacts of missing tissue were assessed. Scanning time, type of the specimens, time to WSIs implementation, and quality control (QC) measures were also considered. The frequency of missing tissue ranged from 2% to 19%. The area size of the missed tissue ranged from 1–70%. In most cases (>75%), the missing tissue area size was <10% and peripherally located. In all cases the missed tissue was fat with or without small entrapped normal breast parenchyma. No missing tissue was identified in WSIs of the core biopsy specimens. QC measures improved images quality and reduced WSI failure rates by seven-fold. A negative linear correlation between the frequency of missing tissue and both the scanning time and the image file size was observed (p < 0.05). None of the WSI with missing tissues resulted in a change in the final diagnosis. Missing tissue on breast WSI is observed but with variable frequency and little diagnostic consequence. Balancing between WSI quality and scanning time/image file size should be considered and pathology laboratories should undertake their own assessments of risk and provide the relevant mitigations with the appropriate level of caution.

Predictors of Invasiveness in Adenocarcinoma of Lung with Lepidic Growth Pattern.

Lung adenocarcinoma with lepidic growth pattern (LPA) is characterized by tumor cell proliferation along intact alveolar walls, and further classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic predominant adenocarcinoma (iLPA). Accurate diagnosis of lepidic lesions is critical for appropriate prognostication and management as five-year survival in patients with iLPA is lower than in those with AIS and MIA. We aimed to evaluate the accuracy of CT-guided core needle lung biopsy classifying LPA lesions and identify clinical and radiologic predictors of invasive disease in biopsied lesions. Thirty-four cases of adenocarcinoma with non-invasive lepidic growth pattern on core biopsy pathology that subsequently were resected between 2011 and 2018 were identified. Invasive LPA vs. non-invasive LPA (AIS or MIA) was defined based on explant pathology. Histopathology of core biopsy and resected tumor specimens was compared for concordance, and clinical, radiologic and pathologic variables were analyzed to assess for correlation with invasive disease. The majority of explanted tumors (70.6%) revealed invasive disease. Asian race (p = 0.03), history of extrathoracic malignancy (p = 0.02) and absence of smoking history (p = 0.03) were associated with invasive disease. CT-measured tumor size was not associated with invasiveness (p = 0.15). CT appearance of density (p = 0.61), shape (p = 0.78), and margin (p = 0.24) did not demonstrate a significant difference between the two subgroups. Invasiveness of tumors with lepidic growth patterns can be underestimated on transthoracic core needle biopsies. Asian race, absence of smoking, and history of extrathoracic malignancy were associated with invasive disease.

Radiographic and Histomorphometric Evaluation of Sinus Floor Augmentation Using Biomimetic Octacalcium Phosphate Alloplasts: A Prospective Pilot Study.

This prospective single-arm clinical study aimed to radiographically and histomorphometrically evaluate the efficacy of the lateral approach for sinus floor elevation (LSFE) using biomimetic octacalcium phosphate (OCP) synthetic bone graft (Bontree®). LSFE using Bontree® was performed on 10 patients (15 implant placement sites) willing to undergo implant surgery, followed by implant placements after 6 months of the healing period. The vertical bone height (VBH) and Hounsfield unit (HU) values at each implant placement site were evaluated radiographically using cone-beam computed tomography at baseline immediately after surgery (T1) and 6 months after surgery (T2). A histomorphometric evaluation of the bone core biopsy specimen was also performed. The mean VBH and HU changes at all sites included a decrease by 0.91 mm and a statistically significant increase by 431.86, respectively, from T1 to T2. The mean ratio of the newly formed bone (23.34% ± 10.63%) was greater than that of the residual bone graft (19.09% ± 8.74%), indicating that Bontree® is effective for new bone formation. This pilot study suggests that Bontree® is a promising bone substitute for LSFE.

Final result for SAFIA trial for neoadjuvant palbociclib in patients with operable luminal breast cancer responding to fulvestrant.

596 Background: Luminal, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) encompasses the most common subtype of breast malignancies. Neoadjuvant strategies of operable BC are primarily based upon chemotherapy (CT), while neoadjuvant hormone therapy (NAHT) has not been well studied in the Middle East and North Africa (MENA) region. However, these tumors might respond poorly to neoadjuvant CT with significant side effects, emphasizing the need to identify patients who could be candidates for NAHT. Methods: The SAFIA trial is a prospective multicentre, international, double-blind, neoadjuvant phase-III trial using upfront 21-gene Oncotype DX Breast Recurrence Score assay (RS) &lt;31) to select operable Luminal HER2-negative patients for induction hormonal therapy with Fulvestrant 500 mg +/– Goserelin (F/G) before randomizing responding patients to F/G + Palbociclib (Cyclin-Dependent Kinase 4/6 inhibitor / CDK 4/6) versus F/G + Placebo. The primary endpoint of this study was the complete pathologic response (pCR) rate. Results: A total of 354 patients were enrolled, leading to 277 patients treated with induction F/G. Of these, 253 responding patients were randomized to F/G fulvestrant with palbociclib or Placebo. Two hundred and thirty patients were evaluable for pathologic response. No statistically significant differences were identified in terms of pCR rates between F/G with palbociclib or placebo: 2% versus 7%, respectively. According to the radiologic responses post- induction F/G, the hormone sensitivity rate was 89.8%, while the clinical benefit of 8–9 months of neoadjuvant F/G was 96%. Safety in the MENA population was acceptable with a grade 3-4 neutropenia rate of 25% in the F/G plus palbociclib arm. The feasibility of performing the 21-gene breast recurrence score assay on core biopsy specimens was optimal in 96.4% of cases. Conclusions: The addition of palbociclib to neoadjuvant F/G did not show any additional benefit in terms of pathologic response, including pCR in neoadjuvant therapy of Luminal HER2-negative BC responding to induction F/G. The use of an upfront 21-gene assay appeared feasible on biopsy specimens, and the identification of tumors with RS&lt;31 allowed to select endocrine sensitive patients, leading ultimately to a 96% clinical benefit with 8–9 months of F/G neoadjuvant therapy. Clinical trial information: NCT03447132. [Table: see text]

NRG-BR007: A phase III trial evaluating de-escalation of breast radiation (DEBRA) following breast-conserving surgery (BCS) of stage 1, hormone receptor+, HER2-, RS ≤18 breast cancer.

TPS613 Background: Approximately 50% of newly diagnosed breast cancers are stage 1, with the majority being ER/PR-positive, HER2-negative. Genomic assays such as the Oncotype DX® have identified patients (pts) with reduced risk of distant metastasis and without benefit from chemotherapy added to endocrine therapy, freeing them from excess toxicity. Genomic assays are also recognized as prognostic for in-breast recurrence (IBR) after BCS and could similarly allow de-escalation of adjuvant radiotherapy (RT). Reducing overtreatment is of interest to pts, providers, and payers. Methods: We hypothesize that BCS alone is non-inferior to BCS plus RT for in-breast recurrence and breast preservation in women intending endocrine therapy (ET) for stage 1 breast cancer (ER &amp;/or PR positive, HER2-negative with an Oncotype DX Recurrence Score [RS] of ≤18). Stratification is by age (&lt;60; ≥60), tumor size (≤1 cm; &gt;1-2cm), &amp; (RS &lt;11, RS 11-18). Pts are randomized post-BCS to Arm 1 with breast RT using standard methods (hypo- or conventional-fractionated whole breast RT with/without boost, APBI) with ≥5 yrs of ET (tamoxifen or AI) or Arm 2 with ≥5 yrs of ET (tamoxifen or AI) alone. The specific regimen of ET in both arms is at the treating physician’s discretion. Eligible pts are stage 1: pT1 (2 cm), pN0, age ≥50 to &lt;70 yrs, s/p BCS with negative margins (no ink on tumor), s/p axillary nodal staging (SNB or ALND), ER &amp;/or PR positive (ASCO/CAP), HER2-negative (ASCO/CAP), and Oncotype DX RS of ≤18 (diagnostic core biopsy or resected specimen). Primary endpoint is in-breast recurrence. Secondary endpoints are breast conservation rate, invasive in-breast recurrence, relapse-free interval, distant disease-free survival, overall survival, patient-reported breast pain, patient-reported worry about recurrence, and adherence to ET. We assume a clinically acceptable difference in of 4% at 10 yrs to judge omission of RT as non-inferior (10-yr event-free survival for RT group is 95.6% vs 91.6% for the omission of RT group). The study is powered to detect a non-inferiority with 80% power and a one-sided α=0.025, assuming that there would be a ramp-up in accrual in the first two years (leveling off in Yrs 3-5); 1,670 (835 per arm) pts are required to be randomized. Conservative loss to follow-up is 1% per yr. Some of the T1a pts screened may have Oncotype DX scores &gt;18, making them ineligible for the study. In the accrual process, pts will be required to register (1,714 pts) to ensure that our final randomized cohort is 1,670 pts. Current accrual (2-2-2022) is 52 screened and 45 randomized. Support: U10CA180868, -180822, NCT04852887. Clinical trial information: NCT04852887.

Evaluating efficacy on tumor biopsy tissue ex vivo before treatment for equitable cancer care.

e13502 Background: Nearly half the world will be diagnosed with cancer. Each year, &gt; 1.7 million new cancers are diagnosed in the US. Worse, systemic therapy turns out to be ineffective in 70% of patients because those drugs do not match the patient’s tumor, imposing a substantial physical, emotional, and financial burden. Each tumor’s distinct composition and heterogeneity can result in diverse responses to the same treatment. There is a critical and urgent need to develop ex vivo personalized cancer models that match patients with the right treatment – before treatment. Here we present a low-cost ex vivo personalized cancer model to rapidly evaluate effectiveness of various therapeutics on intact core biopsy tissue obtained from a patient’s tumor. Objective: The goal of this study is to deliver multiple isolated fluid streams to spatially distinct regions (SDRs) of intact core biopsy specimens for evaluating efficacy of multiple anticancer agents simultaneously. Methods: Core biopsies were generated from xenograft and resected human tumor tissue using 18-gauge and 20-gauge spring-loaded biopsy systems. Xenografts were established using cell lines with known sensitivity and resistance profiles. Fluid streams with anticancer agents, nucleic acid stains, and mock drugs were delivered to spatially distinct regions (SDRs) on intact core biopsy specimens in our patented Personalized Oncology Efficacy Test (POET) lab-chip bioreactors. High content imaging and custom image processing algorithms were used to measure differential activity. Results: No lateral fluid surface conduction, and only minimal lateral diffusion, was observed up to 200 μm deep in tissue. Extent of observed lateral diffusion was within operational parameters of the bioreactor. Integrity of spatially distinct regions on intact core tissue was maintained. Differential activity from anticancer agents compared to mock drugs was observed and quantitatively measured using custom image processing algorithms. Conclusions: The NCI warns that “current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate.” A personalized medicine approach, based on efficacy observed on tissue directly from the patient’s own tumor, is fundamentally better than the current approach. Low-cost next generation ex vivo cancer models that can rapidly match treatments to tumors, such as POET, could transform cancer treatment and make a significant impact on the lives of patients.

A Quality Analysis of Bony Specimens for Optimal Ethylenediaminetetraacetic Acid (EDTA) Decalcification.

Introduction: Weak acids, such as etheylenediaminetetraacetic acid (EDTA), chelate calcium ions from the surface of tissues, decalcifying slowly but preserving molecular structures for ancillary testing. There is a need for optimization of EDTA protocols for specimen decalcification. We studied the effects of EDTA on different types of bony specimens for quality assurance. Methods: Specimens included: proximal femur curettage (0.7 g), fibula shave (1 mm thick, 0.5 g), tibia shave (2 mm thick, 0.9 g), and femur 11-gauge core biopsies. Curettage and shave specimens were placed in formalin then EDTA (Newcomersupply, Middleton, WI, USA) with continuous stirring. Specimens were removed at 24, 48, 72, 96, and 120 hours. Core biopsies were processed in EDTA with heat at 4, 8, 12, and 16 hours. X-ray imaging (Kubtec Xpert 40, Stratford, CT, USA) was obtained. Histological processing was attempted and H&E slides compared to radiologic imaging. Results: Fibula and tibia sections showed appropriate radiolucency at 120 hours and 7 days, respectively. Curettage specimens showed radiolucency of medullary bone at 48 hours. Curettage and fibula sections showed quality histology at 96 hours and 120 hours, respectively. Quality tibia sections were obtained at 7 days, requiring one hour of additional block surface decalcification with 1% HCL solution. Medullary and cortical core biopsies showed quality histology at 12 and 16 hours with heat, respectively. Conclusion: Imaging can determine appropriate decalcification of bony specimens. Medullary bone undergoes more rapid decalcification in EDTA than cortical bone. EDTA decalcification is best used for curettage and core biopsy specimens.