Time Of Initial Biopsy Research Articles

MRI characteristics predict risk of pathological upgrade in patients with ISUP grade group 1 prostate cancer.

This study aims to analyse multiparametric MRI (mpMRI) characteristics of patients diagnosed with ISUP grade group (GG) 1 prostate cancer (PC) on initial target plus systematic MRI/TRUS fusion-guided biopsy and investigate histopathological progression during follow-up. A retrospective single-centre cohort analysis was conducted on consecutive patients with mpMRI visible lesions (PI-RADS ≥ 3) and detection of ISUP-1-PC at the time of initial biopsy. The study assessed clinical, mpMRI, and histopathological parameters. Subcohorts were analysed with (1) patients who had confirmed ISUP-1-PC and (2) patients who experienced histopathological upgrading to ISUP ≥ 2 PC during follow-up either at re-biopsy or radical prostatectomy (RP). A total of 156 patients (median age 65 years) between March 2014 and August 2021 were included. Histopathological upgrading to ISUP ≥ 2 was detected in 55% of patients during a median follow-up of 9.5 months (IQR 2.2-16.4). When comparing subgroups with an ISUP upgrade and sustained ISUP 1 PC, they differed significantly in contact length of the index lesion to the pseudocapsule, ADC value, PI-RADS category, and the MRI grading group (mGG) (p < 0.05). In the ISUP GG ≥ 2 subgroup, 91% of men had PI-RADS category 4 or 5 and 82% exhibited the highest mGG (mGG3). In multivariate analysis, mGG was the only independent parameter for predicting ISUP ≥ 2-PC in these patients. MRI reveals important information about PC aggressiveness and should be incorporated into clinical decision-making when ISUP-1-PC is diagnosed. In cases of specific MRI characteristics adverse to the histopathology, early re-biopsy might be considered. In cases with clear MRI characteristics for clinically significant prostate cancer (e.g., mGG 3 and/or PI-RADS 5, cT3, or clear focal PI-RADS 4 lesions on MRI) and ISUP GG 1 PC diagnosed on initial prostate biopsy, MRI findings should be incorporated into clinical decision-making and early re-biopsy (e.g., within 6 months) might be considered. MRI reveals important information about prostate cancer (PC) aggressiveness. MRI should be incorporated into clinical decision-making when ISUP GG 1 PC is diagnosed on initial prostate biopsy. In cases of specific MRI characteristics adverse to the histopathology, early re-biopsy might be considered.

#2041 Analysis of current real-world management of IgAN in five European countries

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Due to the often progressive nature of IgAN, patients generally face a poor prognosis if the condition is not appropriately controlled. Current treatment recommendations focus on disease management through the use of optimised supportive care, including use of an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB). A physician questionnaire and patient chart review was conducted to investigate the real-world management of IgAN in five European countries. Method Between 21 December 2022 and 6 February 2023, physicians from France, Germany, Italy, Spain and the UK completed a questionnaire on IgAN management, and patient charts from their centres were analysed. Physicians included had to spend &amp;gt;40% of their time in a clinical setting, and have been in practice between 2 and 40 years. Physicians had to have ≥50 CKD stage 1–4 patients under their management, including ≥4 non-dialysis IgAN patients. Patient charts included in the analysis were required to be from patients ≥12 years of age, diagnosed with IgAN and not on dialysis, with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2. Results A total of 261 physicians answered the questionnaire on IgAN management and completed chart audits on 473 of their most recently seen patients. Charts included in the audit were predominantly from male (71%), Caucasian (78%) patients. The mean age of patients was 47 years and 76% were in CKD stage 3 or later. At referral, 66% of patients were receiving an ACEi and/or ARB, 21% were receiving another antihypertensive agent and 6% were taking a sodium-glucose cotransporter 2 inhibitor (SGLT2i). Most patients (88%) had undergone ≥1 kidney biopsy. At the time of initial biopsy, average eGFR was 51.0 mL/min/1.73 m2 and proteinuria was 2.7 g/day. Of patients who had a biopsy, 73% had a mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T) and crescents (C) (MEST-C) score available. Due to biopsy results, 29% of patients initiated systemic steroids and 10% started an SGLT2i. On average, IgAN patients are prescribed five medications, with the number of medications increasing with age. The large majority of patients (92%) were taking an ACEi and/or ARB at the time of the most current visit; prescriptions with an ACEi and/or ARB included combination with an SGLT2i only (36%), with a systemic steroid only (10%), and with both an SGLT2i and a systemic steroid (5%). Less than half (41%) of patients were prescribed an ACEi and/or ARB alone. An ACEi and/or ARB were considered first-line therapy by 81% of physicians. Systemic steroids and SGLT2is were largely thought of as later line treatment options. The majority of physicians (66%) believed that their patients were completely adherent to their treatment regimen. Notably, over one-third (35%) of patients were on second-line therapy or later, with drivers of treatment change including increased proteinuria (31%), decreased eGFR (26%) and side effect management (15%). Over half (54%) of physicians were not completely satisfied with their patients’ overall response to treatment. Physicians anticipated that 74% of their patients would eventually progress to dialysis. Conclusion Many treating physicians are not satisfied with current treatment options for IgAN, with increasing levels of proteinuria, eGFR decline and side effects driving treatment change. Overall, this study indicates that there is a need for more effective and safe treatments for IgAN to prevent disease progression and improve prognosis.

Risk factors associated with tumor upstaging in melanomas treated with Mohs micrographic surgery with melanocytic immunohistochemistry

BackgroundMohs micrographic surgery with melanocytic immunohistochemistry (MMS-I) is increasingly utilized for special site melanoma treatment. Yet, frequency and risk factors associated with upstaging of all-stage cutaneous melanomas treated with MMS-I remain undefined. ObjectiveDetermine upstaging frequency and factors associated with tumor upstaging for all-stage melanomas treated with MMS-I. MethodsIn this retrospective, single-center case series, all cases of invasive and in situ melanoma treated with MMS-I between 2008 and 2018 were reviewed. Patient and tumor characteristics were recorded and compared between tumors that were and were not upstaged from their initial T stage. ResultsOf the 962 melanoma MMS-I cases identified, 44 (4.6%) were upstaged, including 5.6% of in situ and 2.5% of invasive tumors. Risk factors for upstaging included lack of excisional intent at the time of initial biopsy (p<0.01), non-lentigo maligna subtype (p=0.03), female sex (p=0.02), and initial in situ diagnosis (p=0.03). Non-statistically significant characteristics evaluated included patient age (p=0.97), initial Breslow depth (p=0.18), and biopsy type (p=0.24). LimitationsRetrospective study design. ConclusionsAll-stage cutaneous melanomas treated with MMS-I are associated with low upstaging rates. Tumor upstaging is associated with lack of excisional intent, female sex, and in situ tumors.

Topical Treatment of Cutaneous Squamous Cell Carcinoma in Situ and the Impact of Clinical Risk Factors and Positive Histologic Margins at the Time of Diagnosis.

Limited data exist for the efficacy of topical 5-fluorouracil (5-FU) and imiquimod for cutaneous squamous cell carcinoma (cSCC) in situ (cSCCis) with positive histologic margins at the time of diagnosis. Identify the efficacy of topical 5-FU and imiquimod in the treatment of cSCCis with positive histologic margins at the time of diagnosis in relation to clinical risk factors. Pathology records were screened at a single institution from 2014 to 2021 for cSCCis with positive histologic margins. Patients were included if they were treated with curative intent with topical 5-FU or imiquimod. Recurrences were evaluated in relation to multiple clinical risk factors. Of 215 patients treated with 5-FU or imiquimod after biopsy-proven cSCCis, 19 patients had recurrent cSCCis and 1 patient had upstaging to invasive cSCC. Recurrence was more likely in larger lesions at the time of initial biopsy ( p = .033) and in patients treated with topical imiquimod compared with topical 5-FU ( p < .01). Topical 5-FU is an appropriate therapy for cSCCis in the correct clinical scenario. Extra consideration should be taken for use of 5-FU in larger diameter cSCCis lesions. Although limited by sample size, our study does not support the use of imiquimod for cSCCis.

Risk stratification for endometrial hyperplasia and malignancy in women age ≤45 with abnormal uterine bleeding (390)

<b>Objectives:</b> Quality improvement initiative to identify risk factors for endometrial hyperplasia and carcinoma in a South Texas Hispanic patient population aged ≤45 years. <b>Methods:</b> An IRB-approved retrospective case-control study was conducted among women aged <45 with abnormal uterine bleeding (AUB) at a single academic institution. The study included all women aged <45 years who had endometrial sampling performed between 2010 and 2020. Exclusion criteria included age >45 or <18 at the time of initial biopsy, known cancer diagnosis, or known cancer-related syndrome. Several covariates, including demographics, BMI, parity, menstrual history, endometrial stripe thickness, smoking status, medical comorbid conditions, previous and current treatment were analyzed to identify trends in patients with endometrial hyperplasia and malignancy. <b>Results:</b> There were 1,618 women included in the study. Of these 26 (1.6%) had endometrial malignancy, 114 (7%) had EIN, 114 (7%) had benign endometrial hyperplasia, and 1,364 (84.3%) had normal endometrium. The demographic distribution of our study population included 50% Hispanic, 38% Caucasian, 8% African American, 4% unspecified, and <1% Asian. The average age was 37 years with normal endometrium, 38 with benign hyperplasia, 36 with EIN, and 35 years with malignancy. The median BMI for the entire population was 48. Median BMI for women with normal endometrium, benign hyperplasia, EIN, and malignancy was 35, 33, 39, and 43, respectively. Among the 114 women with EIN, 55% were Hispanic, and 41% were Caucasian, and of the 26 women with malignancy, 65% were Hispanic, and 31% were Caucasian. Women with EIN and malignancy had an average endometrial stripe (ES) of 14.5mm and 20mm. Women with normal biopsies had an average ES of 12mm. Heavy menstrual bleeding (63%) followed by oligomenorrhea (24%) were the most common patterns of AUB across all pathologies. The most common comorbid conditions in women with EIN and malignancy were hypertension (31% and 42%, respectively) and diabetes (30% and 46%, respectively). Prior to diagnosis, 49% of women with EIN and 54% of women with malignancy had failed previous medical management of AUB. <b>Conclusions:</b> In a South Texas patient population, women aged <45 years with AUB are at risk of EIN and malignancy. The characteristics most associated with malignancy and hyperplasia were Hispanic ethnicity, increased BMI, thickened ES, heavy menstrual bleeding pattern, and previous treatment failure. A risk stratification tool may be beneficial to help further clarify which patients are at the highest risk and need endometrial sampling versus those patients in whom inappropriate sampling can be avoided.

Bucomaxillofacial cancer and major considerations and treatments: a concise systematic review

Introduction: According to National Cancer Institute, a total of 16,290 new cases of oral cancer are estimated in Brazil in 2017, with 12,370 new cases of oral cavity cancer in men and 4,010 in women corresponding to an estimated risk of 11.54 cases new for every 100 thousand men and 3.92 for each 100 thousand women. In this sense, oral cancer therapy is associated with a multitude of head and neck sequelae including hyposalivation, increased risk of tooth decay, osteoradionecrosis of the jaw, radiation fibrosis syndrome, mucositis, chemotherapy-induced neuropathy, dysgeusia, dysphagia, mucosal lesions, trismus, and infections. Objective: The present study addressed the main considerations about maxillofacial cancer and possible treatments based on the literary findings through a narrative and integrative review. Methods: Clinical studies with qualitative and/or quantitative analysis were included, following the rules of the systematic review-PRISMA. Results and Conclusion: A total of 86 articles were found involving "Bucomaxillofacial Treatment in Cancer Patients". A total of 29 articles were evaluated in full, and 24 were included and discussed in this study. Oral cancer or oral carcinoma is a chronic, complex, multifactorial pathology resulting from the interaction of intrinsic and extrinsic factors that leads to an imbalance in the process of cell proliferation and growth control. There is an association between periodontal disease, nutritional status parameters, and antimicrobial protein levels, in the case of erythroplakia, 70.0 % to 95.0 % of these lesions are cancerous at the time of initial biopsy or will progress to cancer. In invasive squamous cell carcinoma, cancer cells have penetrated deeper layers of the oral cavity and oropharynx. Therefore, preparing a comprehensive treatment plan for cancer patients is essential to help minimize the risks of developing these oral and dental complications. In addition, dentists should consider a patient's ongoing cancer therapy for those patients who come to the dentist while receiving cancer treatment.

Risk of tract recurrence with stereotactic biopsy of brain metastases: an 18-year cancer center experience.

Stereotactic biopsy is increasingly performed on brain metastases (BrMs) as improving cancer outcomes drive aggressive multimodality treatment, including laser interstitial thermal therapy (LITT). However, the tract recurrence (TR) risk is poorly defined in an era defined by focused-irradiation paradigms. As such, the authors aimed to define indications and adjuvant therapies for this procedure and evaluate the BrM-biopsy TR rate. In a single-center retrospective review, the authors identified stereotactic BrM biopsies performed from 2002 to 2020. Surgical indications, radiographic characteristics, stereotactic planning, dosimetry, pre- and postoperative CNS-directed and systemic treatments, and clinical courses were collected. Recurrence was evaluated using RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria. In total, 499 patients underwent stereotactic intracranial biopsy for any diagnosis, of whom 25 patients (5.0%) underwent biopsy for pathologically confirmed viable BrM, a proportion that increased over the time period studied. Twelve of the 25 BrM patients had ≥ 3 months of radiographic follow-up, of whom 6 patients (50%) developed new metastatic growth along the tract at a median of 5.0 months post-biopsy (range 2.3-17.1 months). All of the TR cases had undergone pre- or early post-biopsy stereotactic radiosurgery (SRS), and 3 had also undergone LITT at the time of initial biopsy. TRs were treated with resection, reirradiation, or observation/systemic therapy. In this study the authors identified a nontrivial, higher than previously described rate of BrM-biopsy tract recurrence, which often required additional surgery or radiation and justified close radiographic surveillance. As BrMs are commonly treated with SRS limited to enhancing tumor margins, consideration should be made, in cases lacking CNS-active systemic treatments, to include biopsy tracts in adjuvant radiation plans where feasible.

Risk stratification for endometrial hyperplasia and malignancy in women age ≤ 45 with abnormal uterine bleeding

Quality improvement initiative to identify risk factors for endometrial hyperplasia and carcinoma in a South Texas Hispanic patient population younger than 45 years old. This is a retrospective case control study of women age ≤45 with abnormal uterine bleeding (AUB) at a single academic institution. The study is IRB approved and includes all women ≤45 who had endometrial sampling performed between 2010 - 2020. Exclusion criteria are age >45 or <18 at the time of initial biopsy, known cancer diagnosis, or known cancer-related syndrome. Several covariates including demographics, BMI, parity, menstrual history, endometrial stripe thickness, smoking status, medical comorbidities, previous and current treatment were analyzed to identify trends in patients with endometrial hyperplasia and malignancy. There are 1,618 women included in the study. Of these 26 (1.6%) had endometrial malignancy, 114 (7%) had EIN, 114 (7%) had benign endometrial hyperplasia, and 1,364 (84.3%) had normal endometrium. The demographic distribution of our study population included 50% Hispanic, 38% Caucasian, 8% African American, 4% unspecified, and <1% Asian. The average age was 37 with normal endometrium, 38 with benign hyperplasia, 36 with EIN, and 35 with malignancy. The median BMI for the entire population was 48. Median BMI for women with normal endometrium, benign hyperplasia, EIN, and malignancy was 35, 33, 39, and 43 respectively. Among the 114 women with EIN, 55% were Hispanic and 41% were Caucasian, and of the 26 women with malignancy, 65% were Hispanic and 31% were Caucasian. Women with EIN and malignancy had an average endometrial stripe (ES) of 14.5mm and 20mm. Women with normal biopsies had an average ES of 12mm. Heavy menstrual bleeding (63%) followed by oligomenorrhea (24%) were the most common patterns of AUB across all pathologies. The most common comorbidities in women with EIN and malignancy were hypertension (31% and 42%, respectively) and diabetes (30% and 46%, respectively). Prior to diagnosis, 49% of women with EIN and 54% of women with malignancy had failed previous medical management of AUB. In a South Texas patient population, women ≤45 with AUB are at risk of EIN and malignancy. The characteristics most associated with malignancy and hyperplasia were Hispanic ethnicity, increased BMI, thickened ES, heavy menstrual bleeding pattern, and previous treatment failure. A risk stratification tool may be beneficial to help further clarify which patients are at highest risk and need endometrial sampling vs those patients in whom inappropriate sampling can be avoided.

Implications of a diagnosis of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) on prostate biopsy: a 5-year follow-up study.

In the era of active surveillance of low- and intermediate-risk prostatic cancer, a reconsideration of the implications of a biopsy report of ASAP and/or HGPIN may be timely. We investigated the implications of a diagnosis of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) on prostate biopsy. The rate of re-biopsy and the incidence of carcinoma on repeat biopsy for benign, HGPIN, and ASAP groups were compared. Mean PSA and PSA velocity was also compared between groups. There was an increased risk of developing prostate cancer in the following 5years with a biopsy diagnosis of ASAP compared to benign (20% vs 5.9%, p = 0.009), and with a biopsy of HGPIN compared with benign (14.8% vs 5.9%, p = 0.005). The frequency of repeat biopsy following a diagnosis of ASAP (54.2%) vs. HGPIN (37%) was not significantly different (p = 0.079). The risk of developing prostate cancer was highest following a biopsy with concomitant ASAP and HGPIN compared to benign (50% vs 5.9%, p < 0.001). There was no significant difference in PSA values between the 3 diagnostic groups at the time of initial biopsy (p = 0.206). The findings of this study suggest that a biopsy diagnosis of ASAP ± HGPIN, on either initial or surveillance biopsy, provides support for earlier repeat mpMRI and/or re-biopsy. This may assist in directing to early re-biopsy those patients likely to have intermediate- and high-risk prostate cancer.

Identifying barriers to equitable biomarker testing in underserved patients with NSCLC: A mixed-methods study to inform quality improvement opportunities.

123 Background: Despite recent advances in cancer precision medicine, patients from underserved communities do not have equal access to biomarker testing and targeted therapies. This study used a mixed-methods approach to identify barriers to equitable precision medicine access among underserved patients with non-small cell lung cancer (NSCLC). Methods: Paired national surveys (one clinician-facing and one patient-facing) were developed respectively by the Association of Community Cancer Centers (ACCC) and LUNGevity Foundation. Administered online in spring/summer 2020, the surveys were designed to identify key attitudes/barriers related to biomarker testing, resource needs, and current practice patterns for pertinent stakeholders. Survey data was triangulated with data from focus groups (2 clinician and 6 patient) conducted in fall 2020. The study was approved by Advarra IRB. Results: A total of 99 clinicians responded, with 67% (66/99) representing oncologists from community cancer programs. 248 patients responded to the LUNGevity survey, with 161 coming from the general population and 87 from the LUNGevity network (patients with relatively high income and education levels). Most clinicians surveyed indicated they were “very” (34%) or “extremely” likely (44%) to discuss biomarker testing with NSCLC patients. Academic clinicians, however, were more likely than community-based clinicians to order testing at the time of initial biopsy (76% vs 52%, P =.02). Academic clinicians were also more likely to involve the patient’s family in biomarker testing discussions (85% vs 59%, P =.009). Patient survey results identified that medical oncologists are the primary source of biomarker testing information; 64% of LUNGevity-connected and 37% of underserved patients. Eighty-five percent of LUNGevity-connected patients receive biomarker testing versus 52% for general patients (p &lt; 0.05). Notably, more than a quarter (27%) of underserved patients who have undergone biomarker testing do not know their results. Clinician focus group participants corroborated survey findings that most clinicians receive testing results in 7-14 days, but for 23% of community and 6% of academic clinicians the process can take over 2 weeks. They identified disparities in offering biomarker testing and results to patients with known or presumed low socioeconomic status (SES) and/or health literacy. This was supported by patient survey data, which showed biomarker testing was proactively offered to only 40% of low-SES patients. Conclusions: This study identifies key areas of ongoing need related to equitable biomarker testing. Quality-improvement opportunities exist to address both clinician and patient barriers to guideline-concordant biomarker testing for underserved patients with NSCLC.

Lack of documentation of lymph node examination in patients with squamous cell carcinoma of the lower lip.

Cutaneous squamous cell carcinoma is the second most common cutaneous malignancy with a 5-year disease-specific survival rate of approximately 90%, which decreases dramatically to 50% in the presence of regional lymph node metastases. We sought to examine clinicians' documentation of pertinent neurological symptoms/signs and lymph node palpation at the time of initial biopsy and treatment using lower lip SCC patients as a cohort. Subsequently, we investigated the correlation between clinical and pathologic SCC features and the aforementioned documentation. A single center, retrospective study of all squamous cell carcinomas of the lower lip biopsied over 10years was conducted, and univariate models were implemented to correlate the variables. A total of 66 squamous cell carcinomas of the lip in 63 patients were identified. Neurological signs and symptoms were not documented and only three of the tumors were palpated, therefore statistical analysis was not performed. A lymph node exam was documented in 14 of the 63 patients (22%), and statistical analysis showed that among all variables (age, gender, tumor size, tumor stages, tobacco or alcohol use, or history of skin cancer), only the size of the tumor correlated positively with a lymph node examination (RRE 1.15 [95% CI 1.06-1.25], p < 0.001). Our study illustrates a possible practice gap and quality improvement potential in tumor, neurologic, and lymph node examination and documentation in patients with cutaneous squamous cell carcinoma.

Effect of time to surgical intervention in stage 3 cutaneous melanoma.

e21571 Background: Delay in surgical resection has been found to be associated with poorer overall survival (OS) in patients with stage 1 cutaneous melanoma. However, the impact of surgical timing on survival in stage 3 cutaneous melanoma remains unknown, especially in the era of immunotherapy. We sought to evaluate to the effect of time to definitive surgical intervention on OS in stage 3 cutaneous melanoma at Commission on Cancer accredited institutions. Methods: The National Cancer Database (2012-2016) was used to identify patients who underwent biopsy and definitive surgical intervention of cutaneous melanoma. Time to intervention (TTI) was analyzed from the time of initial biopsy to definitive surgical resection and classified into quartiles, (Q1≤22 days; Q2 = 23-33 days; Q3 = 34-49 days; Q4≥50 days) using χ2 and multivariable logistic regression. Survival was analyzed using Kaplan-Meier and Cox proportional hazard models. Results: We analyzed 4560 patients with a median age of 61 years (18-90) and most patients being non-Hispanic white and male (91.6% and 63%, respectively). Median Breslow thickness was 2.8 mm (0-9.8 mm). Median TTI was 33 days (0-352 days) with a mean OS of 52, 49.8, 48.4, 48.3 months for Q1 to Q4 respectively (p = 0.008). Age ≤50 years, treatment at a comprehensive community cancer center and only 1 positive lymph node (LN) were all associated with Q1 TTI (p = 0.002, p &lt; 0.001 and p &lt; 0.001, respectively). Black race, treatment at an academic facility, &gt; 4 LN positive, &gt; 4 mm thickness, and no administration of immunotherapy were all associated with Q4 TTI (p = 0.002, p &lt; 0.0001, p &lt; 0.0001, p &lt; 0.0001 and p &lt; 0.0001 respectively) on univariate analysis. Patients in Q4 TTI were more likely to be older (OR 1.01, 95% CI 1.00-1.02, p = 0.01), have T2-T4 tumors (OR 1.6, 95% CI 1.2-2.2, p &lt; 0.001), and be treated at an academic facility (OR 2.4, 95% CI 1.8-3.5, p &lt; 0.001) on multivariable analysis. In the survival analysis, multiple positive LNs (2, 3-4, &gt; 4 LNs; HR 1.4, 1.6 and 2.9, p &lt; 0.001), lymphovascular invasion (HR 1.4, p &lt; 0.001), Breslow thickness &gt; 4 mm (HR 1.7, p &lt; 0.001), Charlson-Deyo score ≥2 (HR 1.5, p &lt; 0.001), increasing age (HR 1.03, p &lt; 0.001), and longer TTI (Q3-Q4) (HR 1.2, p = 0.001) were all associated with worse OS. There was no difference in survival based on TTI in patients who had received adjuvant immunotherapy in Q1-Q2 vs Q3-Q4 (p = 0.3). Conclusions: In stage 3 cutaneous melanoma, longer TTI ( &gt; 33 days) was associated with worse OS but may be due to older age, higher T stage, and barriers to access. However, adjuvant immunotherapy may offer protection from delays in definitive surgery.

Cellular Senescence Is Associated with Faster Progression of Focal Segmental Glomerulosclerosis

Background: A current, albeit unproven, hypothesis is that an acceleration of cellular senescence is involved in impaired renal repair and progression of glomerular diseases. Focal segmental glomerulosclerosis (FSGS) is a glomerular disease with a substantial risk for progression to ESRD. However, if and to what extent cell senescence predicts a negative outcome in FSGS is still unknown. Methods: The hypothesis that cell senescence represents a proximate mechanism by which the kidney is damaged in FSGS (NOS phenotype) was investigated in 26 consecutive kidney biopsies from adult FSGS cases (eGFR 72 ± 4 mL/min, proteinuria 2.3 ± 0.6 g/day) who were incident for 2 years in a Northern Italian nephrology center and had a 6-year clinical follow-up. Results: Cell senescence (p16^INK4A, SA-β-galactosidase [SA-β-Gal]) was upregulated by ∼3- to 4-fold in both glomerular and tubular cells in kidney biopsies of FSGS as compared to age-matched controls (p < 0.05–0.01). Tubular SA-β-Gal correlated with proteinuria and glomerulosclerosis, while only as a trend, tubular p16^INK4A was directly associated with interstitial fibrosis. At univariate analysis, basal eGFR, proteinuria, and tubular expression of SA-β-Gal and p16^INK4A were significantly directly related to the annual loss of eGFR. No correlation was observed between glomerular p16^INK4A and eGFR loss. However, at multivariate analysis, eGFR, proteinuria, and tubular p16^INK4A, but not SA-β-Gal, contributed significantly to the prediction of eGFR loss. Conclusions: The results indicate that an elevated cell senescence rate, expressed by an upregulation of p16^INK4A in tubules at the time of initial biopsy, represents an independent predictor of progression to ESRD in adult patients with FSGS.

Nephrotoxicity of calcineurin inhibitors as a risk factor for BK polyomavirus replication after kidney transplantation.

BK polyomavirus-associatednephropathy (PyVAN) is responsible for a significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is closely related to the intensity of immunosuppressive therapy. In a group of 161 newly transplanted patients, we prospectively evaluated 457 protocol renal biopsies performed within the first year after transplantation. Using the calcineurin inhibitors (CI) nephrotoxicity score, the incidence of nephrotoxicity was monitored as a manifestation of excessive immunosuppression. Findings were correlated with clinical evidence of active BK polyomavirus (BKPyV) replication and PyVAN. Compared to the normal histology, nephrotoxicity was associated with more frequent BKPyV viremia and viruria (p = .01 and p < .01, respectively) and more common occurrence of PyVAN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of viremia and viruria (p = .03 and p < .01, respectively), independently of the initial BKPyV status. Toxicity could also be used as a predictor of viremia and viruria (p = .04 and p < .01, respectively) even in the absence of viral replication at the time of initial biopsy. The early histological manifestation of CI nephrotoxicity was associated with significant BKPyV reactivation in the risky first posttransplant year.

P1759NEPHROTOXICITY OF CALCINEURIN INHIBITORS AS A RISK FACTOR FOR BK VIRUS REPLICATION AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims BK virus nephropathy (BKVN) represents a serious complication of kidney transplantation and is responsible for significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is considered a complication of immunosuppressive therapy and is closely related to its intensity. The aim of our prospective study was to evaluate the incidence of subclinical and clinically manifest nephrotoxicity of calcineurin inhibitors (CI) in repeated protocol kidney graft biopsies as a manifestation of excessive immunosuppression and to evaluate its relationship to the PCR confirmed active BKV replication and bioptically proven BKVN during the first year after transplantation. Method In a group of 161 newly transplanted patients we prospectively evaluated 457 consecutive protocol renal biopsies performed within the first year after transplantation. Using the CI nephrotoxicity score, the incidence of nephrotoxicity was monitored. Findings were correlated with laboratory (PCR) and histological evidence of active BK virus (BKV) replication and BKVN. Results When compared to the normal histology, nephrotoxicity was associated with more frequent significant BKV viraemia and viruria (P = 0.02 and P = 0.01, respectively) and more common occurrence of BKVN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of significant BKV viraemia and viruria (P = 0.03 and P = 0.01, respectively), independently of the initial BKV status of the monitored groups. Toxicity could also be used as a predictor of significant viraemia and viruria (P = 0.02 and P = 0.01, respectively) even in the absence of viral replication at the time of initial biopsy. Conclusion Early histological detection of CI nephrotoxicity followed by pre-emptive CI dose reduction might prevent significant BKV reactivation in the risky first posttransplant year. The evaluation whether a regression of histological signs of nephrotoxicity after a CI dose reduction leads to a reduction in BKV replication, and whether a more frequent occurrence of rejection does not complicate further posttransplant course, will be the subject of our further investigation. Supported by grant of Ministry of Health, Czech Republic DRO (FNOL 00098892) – 87-68.

Abstract 3697: High PD-L1 expression and targetable mutations occur independently in NSCLC and are not influenced by smoking or race

Abstract Background: Targeted therapies such as EGFR tyrosine kinase inhibitors (TKIs), and immunotherapy (IO) with PD-L1 inhibitors have revolutionized first-line treatment options for advanced non-small cell lung cancer (NSCLC). Several small studies suggest that high PD-L1 expression rarely overlaps with classic driver mutations, yet it remains unclear how smoking history, race, and stage may influence the interaction between PD-L1 expression and targetable driver mutations. In our racially diverse population with a high proportion of African American patients, we investigated whether high PD-L1 expression occurs concurrently with targetable mutations in EGFR, BRAF, and MET and whether smoking history, stage, or race alters this distribution. Methods: In this retrospective study, we selected all NSCLC patients of any stage at our institution whose tumor samples had undergone both in-house next-generation sequencing (NGS) and PD-L1 staining with the Dako Clone 28.8 antibody between March 2016 to July 2017. Our validated NGS assay, the OncoPlus, detects mutations, deletions, and insertions in 147 clinically reported genes, including all classic driver mutations in lung cancer. Patient demographics, treatments and response data were extracted from the electronic medical record through October 1, 2017. We then used Wilson proportion test and chi-squared analysis to analyze whether PD-L1 expression and actionable mutations varied by race, smoking, age and stage. Results: 114 cases had both PD-L1 staining and NGS analysis available. 71 (62.2%) patients had ≥10 pack year smoking history while 21 (18.4%) patients were never smokers. 41 (35.9%) patients were African American, 62 (54.4%) Caucasian and 7 (6.1%) were Asian. 26 (22.8%) had high expression of PD-L1 (≥50% cells staining positive), and 15 (13.2%), 1 (0.8%), 4 (3.5%), and 6 (5.2%) patients, respectively, had an EGFR, BRAF (V600E), ERBB2, and MET exon 14 skip mutation. 4/26 patients with high PD-L1 expression had a targetable mutation, compared to 22/88 patients with low PD-L1 expression (p&amp;lt;0.001, Wilson test). This distribution did not vary significantly when stratified by race, stage, or smoking history. Conclusions: We present here our institution's novel workflow of obtaining both in-house NGS and PD-L1 staining at time of initial biopsy, in a diverse population with 1/3 African American patients. We demonstrate that high PD-L1 expression and actionable driver mutations infrequently coexist in the same tumor, and this relationship is not driven by smoking, race, or stage. Our results strongly suggest the necessity of obtaining both PD-L1 staining and NGS at time of initial biopsy to identify optimal therapies for patients with advanced disease. Our results imply that patients with actionable driver mutations are unlikely to benefit from later treatment with IO, which we hope to test explicitly in future studies. Citation Format: Noura J. Choudhury, Mansooreh Eghtesad, John Cursio, Sabah Kadri, Lauren Ritterhouse, Jeremy Segal, Aliya Husain, Jyoti D. Patel. High PD-L1 expression and targetable mutations occur independently in NSCLC and are not influenced by smoking or race [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3697.

Abstract P2-03-10: Risk factors for upgrading and upstaging of pre-operative biopsies in ductal carcinoma in situ

Abstract Background: Ductal carcinoma in situ (DCIS), accounts for one fifth of all screen-detected neoplastic breast lesions. Contemporary research in DCIS focuses on separating lesions that need active treatment from those that can be safely left under surveillance. This, in turn, relies on accurate determination of invasive status and DCIS grade at time of initial biopsy. Most previous studies have examined factors associated with upstaging the diagnosis from DCIS to invasive breast cancer (IBC) following surgery, and few have evaluated factors associated with upgrading the diagnosis to a higher grade of DCIS. This is because upgrading has not traditionally influenced clinical management in the way that upstaging has done. However, recent interest in non-operative treatment for low-risk DCIS has meant that accurate determination of grade at time of initial biopsy has become more important. We aimed to compare risk factors for upgrading and upstaging of biopsies in DCIS. Method: We undertook a cohort study of all women diagnosed with DCIS at a large specialist cancer centre between 2000–2014. Information from the clinical records was abstracted, including the pre-operative mammography (MMG) and pathology information from the initial biopsy. We also abstracted pathology information regarding the excised specimen in order to identify women whose diagnosis was subsequently upgraded or upstaged. We looked for factors that were predictive for upgrading or upstaging. Result: A total of 641 women were diagnosed with DCIS at initial biopsy. Of these, 72 (11%) were upgraded: 26 (4%) from grade 1 to grade 2, 2 (0.3%) from grade 1 to grade 3 and 44 (7%) from grade 2 to grade 3. A further 115 (18%) were upstaged to IBC: 20 of these (3%) had grade 1 DCIS on initial biopsy, 47 (7%) had grade 2, 43 (7%) grade 3, and for 5 (1%) biopsy grade was not available. Necrosis on biopsy increased the risk of upgrading (with necrosis: 14% upgraded, without: 10% upgraded, p for difference 0.02) and also of upstaging (with necrosis: 23% upstaged, without: 15% upstaged, p for difference &amp;lt;0.01). Lesions measuring ≥50 mm on MMG were more likely to be upgraded than smaller lesions (0-19 mm: 9% upgraded, 20-50 mm: 9% upgraded, ≥50 mm: 19% upgraded, p for heterogeneity &amp;lt;0.01), while lesions measuring 20-50 mm and ≥50 mm were both more likely to be upstaged than lesions measuring 0-19 mm (0-19 mm: 9% upstaged, 20-50 mm: 23% upstaged and ≥50 mm: 21% upstaged, p for heterogeneity &amp;lt;0.01). Fewer 9G vacuum-assisted biopsies than 14G core biopsies were upgraded (9G vacuum-assisted: 7% upgraded, 14G core: 15% upgraded, p for difference 0.01), while the effect of biopsy method on upstaging was not significant (9G vacuum-assisted: 12% upstaged, 14G core: 16% upstaged, p for difference 0.15). Presence of a palpable lump was not significantly associated with upgrading (palpable lump: 13% upgraded, no palpable lump: 10% upgraded, p for difference 0.19) but increased the risk of upstaging (palpable lump: 23% upstaged, no palpable lump: 16% upstaged, p for difference 0.02). Conclusion: Our findings suggest that consideration of MMG lesion size and necrosis on biopsy may be helpful in selecting low-risk women for non-operative management of DCIS, as may use of the 9G vacuum-assisted method of biopsy. Citation Format: Mannu GS, Groen E, Wang Z, Schaapveld M, Lips E, Chung M, Joore I, Leeuwen Fv, Teerstra J, Winter-Warnars GAO, Darby SC, Wesseling J. Risk factors for upgrading and upstaging of pre-operative biopsies in ductal carcinoma in situ [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-10.

SMAD4 mutation acquisition in the metastatic transformation of pancreatic cancer.

227 Background: SMAD4 mutations have been associated with worse prognosis and metastatic disease in patients with pancreatic cancer. It is unknown whether pancreatic cancers that metastasize acquire this mutation at disease onset or closer to the time of metastatic progression. Methods: Biopsies from 26 patients with known resectable and unresectable pancreatic cancer were analyzed via next generation DNA sequencing for 153 mutations associated with solid tumors, including SMAD4. Imaging and clinical data regarding extent of disease were reviewed at the time of each specimen collection. Results: 46% of patients had metastatic disease at the time of initial biopsy, and of these patients 83% had detectable SMAD4 mutations. Amongst patients with no evidence of metastatic disease, 11 of 14 had intact SMAD4. SMAD4 mutations were associated with metastatic spread of disease, Χ2= 7.46, p = .006. Eight patients with localized, SMAD4 intact pancreatic cancer had repeat biopsies at the time of metastatic progression that showed SMAD4 mutations not previously identified at the time of diagnosis. 2 of 3 patients with SMAD4 mutations and localized disease at diagnosis, developed metastatic disease within 7 months of biopsy. Mean time to metastatic disease development in localized disease patients with mutated and intact SMAD4 were 3.15 and 17 months, respectively, p = .01. Mean CA 19-9 levels in patients with mutated and intact SMAD4 were 10172 and 4117 U/mL, respectively, p = .04. Non-metastatic patients with SMAD4 mutations who developed metastatic disease shortly after initial biopsy only developed rising CA 19-9 levels once radiographic metastases were visible. Conclusions: SMAD4 mutations were ultimately acquired by each patient who presented with localized disease and then developed metastases, and are likely involved in the transformation from localized to metastatic disease. SMAD4 mutations are statistically associated with an earlier time to metastatic disease development in patients with localized disease at diagnosis. SMAD4 mutations precede CA 19-9 elevations in patients that develop metastatic disease and may represent a more sensitive biomarker to identify patients at greater risk for developing metastatic disease.

Abstract P3-01-17: A technique for preoperative axillary lymph node tattooing in patients with breast cancer

Abstract Purpose: To describe the ultrasound technique for tattooing axillary lymph nodes (ALNs) after lymph node (LN) biopsy in patients with breast cancer. Background: Preoperative evaluation of metastatic disease within ALNs in patients with newly diagnosed breast cancer has significant prognostic value and is quickly becoming routine, particularly in the neoadjuvant setting. A recent study showed tattooed LNs are visible intraoperatively and on histological evaluation months following the tattooing procedure. These results suggest that LN tattooing can obviate the need for additional localization procedures during axillary staging, such as wire localization. Given the increasing use of preoperative ALN biopsy, a robust technique to insure proper LN tattoo marking is proposed. Methods and Technique: Tattooing was performed under real-time US guidance using a 5-cm long 21-gauge hypodermic needle attached to a 1 mL tuberculin syringe containing 1 mL carbon suspension tattoo ink (SPOT™, GI-supply Inc). Imaging was performed with the patient in a supine oblique position with the patient's arm over their head. The anatomically anterior and lateral aspects of the node and perinodal fat were marked with ink. The only regions of the LN not targeted for ink tattooing were the hilum and the posterior cortex and perinodal fat. At least 0.5 mL of ink was used. Results: Optimal technique for intraoperative visualization was determined to be tattooing the anatomically anterior and lateral aspects of the LN cortex and the adjacent perinodal fat using at least 0.5mL of ink. Tattooed LNs which had undergone biopsy and tattooing months prior to surgery were visible intraoperatively and on histological evaluation. Factors contributing to less optimal visualization of the tattooed lymph node included: using less than 0.5mL of ink, tattooing only the superficial cortex and not the perinodal fat, and tattooing a portion of the LN that was not visible with the patient in the operative position. Discussion: The most easily accessed portion of the LN during the US procedure may not be the portion of the LN most easily seen intraoperatively. Locating and tattooing the anatomically anterior and lateral aspects of the LN, regardless of the patient position and orientation of the ultrasound probe, is the primary challenge. Doing so will maximize the likelihood that the tattoo ink will be visible by the surgeon when the patient is in a supine position with the arm abducted 90 degrees using an axillary incision. Tattooing using less than 0.5 mL resulted in suboptimal visualization. Using a larger volume of ink may be judged necessary for larger LNs, very fatty axillae, and for deeply seated nodes. Other reports in the medical literature suggest cutaneous tattooing can result in ink within ALNs. In patients with ipsilateral cutaneous tattoos, an alternative method of marking any biopsied LNs should be considered to avoid false positives associated with prior migration of the cutaneous tattoo ink to the LN. Tattooing of ALNs under ultrasound guidance is a straightforward technique which can be performed at the time of initial biopsy and obviates the need for future preoperative wire localization of the LN. Citation Format: Wapnir IL, Downey JR, Lipson JA, Ikeda DM. A technique for preoperative axillary lymph node tattooing in patients with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-17.

Metaplastic Breast Cancer: A Clinicopathologic Correlation of Histologic Subtype on Disease Control

Purpose/Objective(s): Metaplastic breast cancer is a rare type of breast cancer, associated with poor prognosis, and exhibits heterogeneity in presentation and outcome. There are conflicting reports on the significance of specific histopathology on clinical outcome. The goal of this study was to analyze clinical outcomes in metaplastic breast carcinoma and any potential association with histologic subtypes. Materials/Methods: With IRB approval, single institution data were obtained for all patients diagnosed with non-metastatic, metaplastic breast cancer between 2002 and 2013. All cases were re-evaluated by dedicated breast pathologists and confirmed as metaplastic breast cancer. Histologic subtype was divided into four categories: spindle, squamous, matrix-producing, and other. Demographic information and clinical presentation were correlated with histologic subtype. Univariate and multivariate Cox proportional hazards models were performed to evaluate the impact of histologic variables on outcome. Kaplan Meier methods evaluated localrecurrence-free and distant-metastasis-free survival. Results: One hundred thirteen female patients with non-metastatic, metaplastic breast cancer were identified, all of whom underwent needle core or excisional biopsy followed by surgical resection. Median age was 60 and median follow up was 31 months. The majority of patients received chemotherapy and/or radiation (74% and 54%, respectively). Only 46/113 (41%) were identified to have metaplastic breast cancer at the time of initial biopsy. At resection, 94% were Bloom Richardson grade III and 67% were triple negative. Among the 113 patients, the following histologic subtypes were observed: 14 (12%) spindle, 51 (45%) squamous, 32 (27%) matrix-producing, and 18 (16%) other. There was no difference in the frequency of T and N stage observed at presentation among different histologic subtypes (pZ0.4 and 0.17, respectively). Univariate analysis demonstrated that histologic subtype did not significantly correlate with local (pZ0.54) or distant (pZ0.83) control. Two year local control rates per Kaplan Meier analysis are as follows: spindle 77%, squamous 90%, matrix-producing 97%, and other 97%, with no statistically significant difference among subtypes (pZ0.53). For the same histologic subtypes, 2 year distant-metastasis-free survival rates were 84%, 87%, 86%, and 81%, respectively (pZ0.83). Conclusion: This study represents one of the largest reported experiences of the role of histologic subtype on outcomes in metaplastic breast cancer. Metaplastic breast cancer is infrequently diagnosed at biopsy. The majority are high grade and triple negative. Histologic subtype does not significantly impact rates of local recurrence or distant metastasis. Author Disclosure: C.A. Berriochoa: None. C.M. Leyrer: None. S. Agrawal: None. A. Donaldson: None. R. Stewart: None. H. Moore: None. R.D. Tendulkar: None. B. Calhoun: None.