Early Adjuvant Research Articles

Impact of Autonomic Nerve Invasion on Biochemical Recurrence for Intermediate Risk T3a Prostate Cancer With Negative Surgical Margins After Radical Prostatectomy

OBJECTIVETo assess the impact of autonomic nerve invasion (ANI) on subsequent biochemical recurrence (BCR) or early adjuvant therapy in the patients with extraprostatic spread (EPS) and negative margins after radical prostatectomy (RP). METHODSA total of 218 men with EPS (T3a) and negative margins were identified who underwent radical prostatectomy in Western Australia from January 2014 to December 2016. The t-test, Pearson chi-square test and Kaplan-Meier method with the log-rank test were used to evaluate differences between the ANI and non-ANI. Univariate and multivariable Cox proportional hazard regression models were applied to assess the impact of these parameters on BCR or early treatment and a model calibration was performed by the internal validation method. RESULTSANI group had a significant higher incidence in BCR or early adjuvant therapy compared to non-ANI group (hazard ratio 1.94, 95% CI 1.12-3.37, p=0.02). Further analyses showed that ANI was significantly associated with BCR or early adjuvant therapy (hazard ratio 3.03, 95% CI 1.28-7.15, p=0.01) in intermediate risk cases (Gleason sum (GS)=7, i.e. International Society of Urological Pathology (ISUP) groups 2/3) but not in high risk group (GS≥8/ISUP 4/5). CONCLUSIONFor the patients with EPS (T3a) and negative margins, ANI significantly and independently increases the chances of BCR or early adjuvant therapy for intermediate risk disease (GS=7/ISUP 2/3) but it is not an independent predictor for high risk disease (GS≥8/ISUP 4/5). This provides a simple cost effective method to further stratify margin negative intermediate risk T3a prostate cancer.

Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma.

With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. BRAF-targeted therapy is a standard of care in resected stage III-IV melanoma, while anti-programmed death-1 (PD1) immunotherapy is now a standard of care option in resected stage IIB through IV disease. With both modalities, recurrence-free survival and distant-metastasis-free survival are improved by a relative 35-50%, yet no improvement in overall survival has been demonstrated. Neoadjuvant anti-PD1 therapy improves event-free survival by approximately an absolute 23%, although improvements in overall survival have yet to be demonstrated. Understanding which patients are most likely to recur and which are most likely to benefit from treatment is now the highest priority question in the field. Biomarker analyses, such as gene expression profiling of the primary lesion and circulating DNA, are preliminarily exciting as potential biomarkers, though each has drawbacks. As in the setting of metastatic disease, markers that inform positive outcomes include interferon-γ gene expression, PD-L1, and high tumor mutational burden, while negative predictors of outcome include circulating factors such as lactate dehydrogenase, interleukin-8, and C-reactive protein. Integrating and validating these markers into clinically relevant models is thus a high priority. Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.

A hybrid approach: a safe option for surgical treatment of early-stage cervical cancer.

The aim of the study was to describe the surgical treatment of early-stage cervical cancer (CC) via minimally invasive surgery (MIS) and a sequential hybrid approach combining MIS and mini-Pfannenstiel. Evaluate sentinel lymph node (SLN) detection using a hybrid tracer (ICG-99m Tc nanocolloid). Prospective, observational, descriptive, single-center study conducted at Son Espases University Hospital between January 2019 and September 2021. Patients with early-stage CC (FIGO 2018 IA1 with ILV-IIA1) who underwent surgical treatment with a follow-up of at least one year were included. Thirty early-stage CC patients were included, of whom four (13.3%) were upstaged due to positive SLNs. In these cases, laparotomy was avoided, and paraaortic lymphadenectomy was performed via MIS approach. Twenty-six patients had a radical hysterectomy: 15 underwent a hybrid approach, 10 laparoscopy, and one laparotomy. Patients undergoing laparoscopic surgery had a smaller estimated tumor size than those undergoing the hybrid approach. The overall SLN detection rate was 96.1%, with 88.5% of cases occurring bilaterally. Five out of 26 patients (19.2%) presented SLN macrometastases, and five (19.2%) had atypical drainage. Surgery refined staging in 33.3% (10/30) of cases. No recurrences were reported after an average follow-up of 32 months. MIS for SLN avoids laparotomy leading to rapid recovery and early adjuvant treatment initiation in nodal metastasis. In our study, tumor size is an important clinical implication in the surgical approach to be used. The hybrid tracer provided a high detection rate and combined the advantages of the two tracers. The hybrid approach has a quick recovery and optimal results.

Study of options and procedures in reconstruction of post mastectomy breast defects in a regional cancer centre

Background: Post mastectomy autologous breast reconstruction is challenging and involves restoring the patients lost structure and prepping the patient for adjuvant therapy and also psychosocial benefits that comes with early breast reconstruction. We analysed latissimus dorsi flap, transverse rectus abdomenis flap, deep inferior epigastric perforator flap and thoracoabdominal flap. Aim was to reconstruct post mastectomy defect using various methods, to enable the patient to receive early adjuvant therapy. Objectives were to study the various procedures used for post mastectomy defect autologous breast reconstruction. To evaluate the reliability of various flaps used. To evaluate the complications of flaps and their management. To assess the advantages and disadvantages of each flap. Methods: 42 post mastectomy defect patients reconstructed with 4 flaps over 24 months, included in the study and results analysed. Results: In 42 cases, latissimus dorsi flap was done in 11 cases, transverse rectus abdominis flap was done in 6 cases, deep inferior epigastric perforator flap was done in 3 cases and thoracoabdominal flap was done in 22 cases. Total flap loss in 1 case and partial flap loss in 6 cases was seen. Conclusions: Immediate autologous breast reconstruction is helpful in making the patient ready for upcoming adjuvant therapy along with psychosocial benefits. We have analysed 4 different types of flaps and compared their advantages and disadvantages. We found that thoracoabdominal flap is a good option of immediate coverage in low socioeconomic class patients and ones with terminal disease.

Zonal origin of prostate cancer: comparison of long-term outcomes after radical prostatectomy

PurposeTo assess the impact of zonal origin on positive bladder neck (BN) margins and prostate-specific antigen (PSA) failure or early adjuvant therapy in the patients with complete long-term follow-up after radical prostatectomy (RP).MethodsA set of 4512 men were identified who underwent RP in Western Australia (WA) from March 2000 to December 2016 and had complete long-term follow-up. The t-test, Pearson chi-square test and Kaplan–Meier method with the log-rank test were used to evaluate differences between the transition zone (TZ) and peripheral/central zone (PZ/CZ) cancer. Univariate and multivariable Cox proportional hazard regression models were applied to assess parameters on PSA failure and early treatment.ResultsThe positive BN margin rate for TZ cancer fell significantly over the study period. However, BN margin rates increased for PZ/CZ cancer over the time. Data of 4512 patients with median follow-up of 9.1 years confirmed that the high-risk TZ tumours with negative margins had a significant lower rate of PSA failure or early treatment compared to those high-risk PZ/CZ tumours with negative margins.ConclusionProstate cancer zonal origin significantly impacts long-term biochemical outcomes in high-risk and margin-negative patients. BN invasion with margin involvement is more frequent in the TZ cancer and can be reduced by pre-operative identification of cancer zonal origin and adjustment of surgical procedures.

MP61-07 EARLY SECONDARY TREATMENT OF LYMPH NODE POSITIVE PROSTATE CANCER AFTER RADICAL PROSTATECTOMY IS ASSOCIATED WITH AGGRESSIVE TUMOR FEATURES AND DETECTABLE PROSTATE SPECIFIC ANTIGEN

You have accessJournal of UrologyCME1 Apr 2023MP61-07 EARLY SECONDARY TREATMENT OF LYMPH NODE POSITIVE PROSTATE CANCER AFTER RADICAL PROSTATECTOMY IS ASSOCIATED WITH AGGRESSIVE TUMOR FEATURES AND DETECTABLE PROSTATE SPECIFIC ANTIGEN Daniel Triner, Ji Qi, Udit Singhal, Michael Sessine, Kevin Ginsburg, Brian Lane, and Todd Morgan Daniel TrinerDaniel Triner More articles by this author , Ji QiJi Qi More articles by this author , Udit SinghalUdit Singhal More articles by this author , Michael SessineMichael Sessine More articles by this author , Kevin GinsburgKevin Ginsburg More articles by this author , Brian LaneBrian Lane More articles by this author , and Todd MorganTodd Morgan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003319.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with lymph node positive (pN+) disease found at the time of radical prostatectomy (RP) and pelvic lymphadenectomy (PLND) are at high risk of disease recurrence and progression. There is ongoing debate with regards to optimal care of pN+patients. While data supports the use of adjuvant androgen deprivation therapy (ADT) with or without radiation (RT), most guidelines include observation as an alternative. We sought to understand contemporary practice patterns of patients with pN+prostate cancer (PCa) in a diverse, statewide quality collaborative. METHODS: Patients in the Michigan Urologic Surgery Improvement Collaborative (MUSIC) with PCa who underwent RP with PLND and pN+on final pathology and 12 months follow up between March 2012 and Feb 2021 were identified. Patients who received neoadjuvant therapy were excluded. The primary outcome was early post-RP treatment (ADT, RT, ADT+RT) within 12 months of diagnosis, which was categorized as either adjuvant (PSA<0.1 ng/ml) or salvage (PSA≥0.1 ng/ml). Time to any post-RP treatment and type of treatment were secondary outcomes. Multivariable logistic and Cox regression models were fit to identify factors associated with post-RP treatment. Kaplan-Meier analysis was performed to assess treatment-free survival. RESULTS: We identified 425 patients who had pN+disease at the time of RP, of which 280 (66%) underwent early post-RP treatment (86 adjuvant and 194 salvage) and 145 (34%) were observed. One year treatment-free survival for patients with first post-RP PSA≥0.1 was 18% (95% CI 14%-24%) compared to 58% (95% CI 51%-65%) for PSA<0.1 ng/ml (p<0.001). In the multivariable Cox model, pathologic grade group, tumor stage, margin status, first post-RP PSA, and race were associated with time to secondary treatment (p<0.05 for each). Of 145 patients on initial observation, 23% had post-RP PSA≥0.1. ADT was most common early adjuvant therapy (45.4%), followed by ADT+RT (36%), RT alone (17.4%), and other (1.2%) CONCLUSIONS: Most patients with pN+PCa in MUSIC received early post-RP treatment and men with a first post-RP PSA<0.1ng/mL had improved secondary treatment free survival. Early treatment, which was predominantly ADT±RT, is influenced by aggressive disease features and detectable post-RP PSA. Nearly one out of four patients with pN+cancer not receiving early post RP treatment had a detectable PSA, suggesting an opportunity for quality improvement by increasing use of postoperative therapy. Source of Funding: Blue Cross Blue Shield of Michigan © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e855 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Triner More articles by this author Ji Qi More articles by this author Udit Singhal More articles by this author Michael Sessine More articles by this author Kevin Ginsburg More articles by this author Brian Lane More articles by this author Todd Morgan More articles by this author Expand All Advertisement PDF downloadLoading ...

Robotic-assisted laparoscopic radical prostatectomy: Initial outcomes of 500 cases.

We aimed to present our experience of robot-assisted laparoscopic radical prostatectomy (RARP). The study was a retrospective review of 500 patients who underwent RARP between March 2015 and July 2021 in our clinic. A transperitoneal approach was used in all patients. All patients had clinically organ-confined prostate cancer (≤ cT2c). The mean age of the patients was 64.6 ± 5.7 years. The median PSA was 11.4 ng/dL (range 0.3-92.7). The mean operative time was 183.5 min. Positive surgical margin rate was 19.4%. During a mean follow-up of 23.5 months, 96 patients (19.2%) received adjuvant radiotherapy due to the biochemical recurrence and 28 patients (16%) with lymph node positivity received early adjuvant hormone therapy. Considering the continence rates, 69% of the patients were total continence in the 3rd month, while this rate increased to 83 in the 6th month and 91% in the 12th month. RARP is a safe and feasible method for experienced centers with patient comfort, surgeon comfort, and successful oncological and functional results.

The complementary role of lymphovascular invasion and perineural invasion in the TNM staging process of rectal cancer.

The aim of this study is to clarify the association between lymphovascular invasion (LVI) and/or perineural invasion (PNI) and the clinical characteristics and prognostic importance of rectal cancer, to provide a basis for early adjuvant treatment of rectal cancer. We retrospectively analyzed patients diagnosed with rectal cancer. This study involved rectal cancer tissue samples were obtained by surgical methods. Data on histological form, tumor classification, tumor size, gross growth pattern, blood and lymphatic vessel invasion, and PNI of the slice by HE staining were obtained from pathological examination. Immunohistochemical analysis of tissue samples was performed to determine p53 and EGFR expressions. There were 330 rectal cancer patients included in the study. LVI and/or PNI can be used as a high-risk factor for the prognosis of rectal cancer, predict prognostic survival, and guide adjuvant therapy. The detection rates of LVI and PNI were 32.1% and 16.1%. Differentiation grade, Union for International Cancer Control staging, tumor-lymph node-metastasis staging are significantly related to LVI or PNI. Multivariate logistic regression analysis shows that poor differentiation and N ≥ 1 can be used as independent risk factors and predictive factors for LVI. At the same time, poor differentiation and T > 3 is an independent risk factor for PNI. Only poor differentiation is the risk factor for poor prognosis in Cox risk regression analysis. In addition, the simultaneous occurrence of LVI and PNI is an independent prognostic factor.

The impact of neoadjuvant treatment (NAT) on surgery in early breast cancer (EBC): A real-world data study.

e12609 Background: NAT is being used with increasing frequency in the multimodal treatment of EBC. Oncologically, NAT provides an opportunity to assess response to early systemic therapy and tailor adjuvant treatment. The surgical objective of NAT is down staging the tumor, which may lead to improved chances of breast conservation surgery; potentially decreasing surgical morbidity. Down staging of axillary disease may also lead to minimizing the need for complete axillary lymph node dissection (ALND) and its associated surgical morbidity. We aimed to describe the potential impact of NAT on surgical de-escalation in the primary breast tumor and axilla in patients (pts) with HER2-positive, node-positive EBC treated in the community setting. Methods: We conducted a retrospective cohort study using a nationwide US electronic health record-derived de-identified database (Flatiron Health). Pts were diagnosed from Jan 1, 2011 to Sep 30, 2021, had reported clinical staging cN≥1, underwent primary breast surgery (index date), and had records indicating initiation of systemic treatment before surgery. Early clinical benefit includes, post-NAT: a) nodal pathologic complete response (pCR; pN=0); b) pCR (absence of residual invasive disease in the breast and axillary lymph nodes at NAT completion, subsequently confirmed at primary surgery); c) down staging (lowered T or N stage). Surgical operations recorded at index date were ALND and sentinel node excision (SNE), mastectomy (MT), and lumpectomy (LT). Results: 174 pts were included. At diagnosis, median age was 55 years, 162 pts (93%) presented with invasive ductal carcinoma, and &lt;5 had bilateral BC. 124 pts (71%) were treated with dual HER2 blockade. As for early clinical benefit, nodal pCR was achieved in 106 pts (61%), pCR in 90 (52%), and down staging in 137 (79%). Types of surgical procedure for the axilla were SNE only for 62 pts (36%), ALND only for 84 (48%), and SNE and ALND for 26 (15%). Surgical procedures for the breast were MT for 118 pts (68%), of which 59 were bilateral, and LT for 55 (32%). Compared with not achieving nodal pCR, achieving nodal pCR was associated with increased odds of SNE only (odds ratio [OR] 2.59 [95% confidence interval (CI) 1.28, 5.53]), decreased odds of ALND (OR 0.47 [95% CI 0.23, 0.93]), increased odds of LT (OR 2.05 [95% CI 1.00, 4.39]), and decreased odds of MT (OR 0.47 [95% CI 0.22, 0.96]). Conclusions: In a real-world population of pts with HER2-positive EBC, NAT use was associated with early clinical benefit, potentially leading to less invasive primary surgery of the breast and axilla. The high use of MT and bilateral MT despite a high pCR rate demonstrates the multiple factors at play behind surgical and pt decision making. These data illustrate how NAT use can benefit pts by de-escalating surgical treatment options. Limitations include the modest sample size and lack of association between early and long-term clinical benefit.

Validation of the 31-gene expression profile test to stratify melanoma-specific survival in an unselected, prospectively tested cohort of patients with stage IIB-III cutaneous melanoma.

e21538 Background: Given recent FDA extended approval of Pembrolizumab for stage IIB-IIC cutaneous melanoma (CM) patients, it is critical to risk-stratify patients to balance potential benefits versus toxicities of adjuvant therapy. The 31-gene expression profile (31-GEP) is a validated test for CM for risk of recurrence or metastasis prognosis in patients with stage I-III CM. A low-risk (Class 1A) 31-GEP result is associated with lower recurrence risk and higher melanoma-specific survival than an intermediate (Class 1B/2A) or high-risk (Class 2B) result. To validate the 31-GEP’s ability to stratify patients’ risk in an unselected, prospectively tested cohort of therapy-eligible CM patients, we collaborated with the National Cancer Institute and the Surveillance, Epidemiology, and End Results (SEER) program. Methods: A linkage was conducted between SEER registries’ CM cases diagnosed 2012-2018, and 31-GEP tested patients between 2013-2020. A de-identified dataset was used for the analysis. Kaplan-Meier analysis with log-rank test was used to analyze patient melanoma-specific survival (MSS) in the overall cohort and the subset of patients with potential adjuvant therapy access: stage IIB-III melanoma (n = 615). Results: In the overall cohort of patients (N = 5,225), those with a 31-GEP Class 1A result had higher 3-year MSS than patients with a Class 2B result (99.7% vs. 90.4%, p &lt; 0.001). In multivariable Cox regression analysis, a Class 2B result was an independent significant predictor of MSS (HR = 5.71, p = 0.01), as were age (HR = 1.05, p &lt; 0.001), SLN positivity (HR = 2.42, p = 0.02), and T2b (HR = 8.29, p = 0.025) and T4b (HR = 11.99, p = 0.009) tumors. In the subset of patients with stage IIB-III melanoma, those with a 31-GEP Class 1A result had higher 3-year MSS (98.8% vs. 82.4%, p = 0.02) than patients with a Class 2B result. Patients with a Class 2B result had a five and a half times higher event rate than those with a Class 1A result for MSS (5.5% [21/382] vs. 1.0% [1/105]). Conclusions: In a large, unselected, prospectively tested cohort of patients with stage I-III CM, the 31-GEP stratified patient risk of dying from melanoma, validating previous studies. While the 31-GEP identified a subgroup (Class 1A) of traditionally high-risk patients (stage IIB-III CM) who had a &gt; 98% MSS over three years, it can also facilitate identifying patients who could warrant earlier adjuvant therapy with a higher 31-GEP class designation.

Clinical Outcomes of Rose Bengal Mediated Photodynamic Antimicrobial Therapy on Fungal Keratitis with Their Microbiological and Pathological Correlation

Purpose To report the clinical outcome of Photodynamic Antimicrobial Therapy (PDAT) with Rose Bengal (RB) used as an early adjuvant therapy in patients with fungal keratitis and their microbiological and pathological correlation. Methods Patients with microbiologically confirmed fungal keratitis underwent PDAT-RB along with topical natamycin 5% drops hourly and oral ketoconazole 200 mg twice a day. This was performed by applying rose bengal (0.1%) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm2 custom-made green LED source for 15 minutes (5.4 J/cm2). The corresponding fungal isolates were tested in vitro using PDAT-RB and corneal buttons were evaluated for correlation. Results Following informed consent, seven patients (male-5, female-2, mean age 47.7 years) with fungal keratitis were recruited. There were 3 cases each of Fusarium and Aspergillus flavus and 1 case of Acremonium sp. The average vertical and horizontal diameters of the corneal infiltrate were 4.12 ± 0.55 and 3.99 ± 1.19 mm, respectively. The average depth of corneal involvement was 283 ± 75.27µ as measured by anterior segment OCT. The clinical resolution was achieved in the cases with Fusarium keratitis with an average time of 39 days. Three cases of A. flavus and a single patient with Acremonium keratitis worsened and needed therapeutic keratoplasty (TPK) for resolution. Post-TPK, the corneal tissues grew A. flavus in one out of three cases and Acremonium sp. in one case. In vitro PDAT-RB experiment was performed on the corresponding fungal isolates grown from the corneal scraping. PDAT-RB produced clear inhibition of Fusarium and Acremonium sp. with no effect on the growth of A. flavus. Histopathologically, 2 out of 4 (50%) corneal buttons showed fungal filaments. Conclusions While the in vitro and in vivo results of PDAT-RB matched for Fusarium sp. and Aspergillus flavus keratitis being favourable in the former and non-favourable in the latter, these results were discrepant in Acremonium sp.

Prognostic factors for hearing outcomes in patients that undergo adjuvant hyperbaric oxygen therapy for sudden sensorineural hearing loss.

IntroductionThe aim of this study is to explore the potential factors in hearing outcomes and verify the role of oxidant‐antioxidant equilibrium on the prognosis of sudden sensorineural hearing loss (SSNHL) treated with hyperbaric oxygen therapy (HBOT).MethodsNinety‐two patients who were diagnosed with SSNHL between January 2018 and December 2019 in our hearing clinic center were included in this study. All patients were treated with intravenous dexamethasone, and 72 cases were treated with additional HBOT for 10 consecutive days. Peripheral blood was collected prior to any treatment to determine the blood cell count and hemoglobin (HGB), hematocrit (HCT), and superoxide dismutase (SOD) levels. Pure tone audiometry was measured before and after treatment. Complete and overall recovery rate was evaluated. Multivariate logistic analysis was used to identify prognostic factors.ResultsThe rate of overall recovery was significantly higher in the patient with combined therapy compared to patients treated with steroids only (51.4% vs 25.0%, p = .036). The levels of HGB, HCT, and SOD were much higher in the patients with better hearing outcomes (p = .027, .033, and .011, respectively). Multivariate logistic analysis demonstrated that patients with higher initial hearing thresholds, or hearing loss at overall frequency, were more prone to have poor hearing gains after HBOT.ConclusionHBOT is effective as an early adjuvant therapy for SSNHL. Hearing loss at low frequency, low initial hearing thresholds, as well as high HBG, HCT, and SOD levels are positive prognostic factors for SSNHL patients treated with HBOT.

Predictive Value of K i -67 Index in Evaluating Sporadic Vestibular Schwannoma Recurrence: Systematic Review and Meta-analysis.

Introduction K i -67 is often used as a proliferation index to evaluate how aggressive a tumor is and its likelihood of recurrence. Vestibular schwannomas (VS) are a unique benign pathology that lends itself well to evaluation with K i -67 as a potential marker for disease recurrence or progression following surgical resection. Methods All English language studies of VSs and K i -67 indices were screened. Studies were considered eligible for inclusion if they reported series of VSs undergoing primary resection without prior irradiation, with outcomes including both recurrence/progression and K i -67 for individual patients. For published studies reporting pooled K i -67 index data without detailed by-patient values, we contacted the authors to request data sharing for the current meta-analysis. Studies reporting a relationship between K i -67 index and clinical outcomes in VS for which detailed patients' outcomes or K i -67 indices could not be obtained were incorporated into the descriptive analysis, but excluded from the formal (i.e., quantitative) meta-analysis. Results A systematic review identified 104 candidate citations of which 12 met inclusion criteria. Six of these studies had accessible patient-specific data. Individual patient data were collected from these studies for calculation of discrete study effect sizes, pooling via random-effects modeling with restricted maximum likelihood, and meta-analysis. The standardized mean difference in K i -67 indices between those with and without recurrence was calculated as 0.79% (95% confidence interval [CI]: 0.28-1.30; p = 0.0026). Conclusion K i -67 index may be higher in VSs that demonstrate recurrence/progression following surgical resection. This may represent a promising means of evaluating tumor recurrence and potential need for early adjuvant therapy for VSs.

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP)

IntroductionIn contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives.Material and methodsBetween January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval.ResultsDepending on the median time interval of 55 days (d) (95% CI 51.42–84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%).Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months).The 5-year OS rate for all patients involved was 71% (95% CI 0.55–0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48–1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42–0.80; X2(1) = 1.16, p = 0.281).Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75–0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89–1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57–0.95; X2(1) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59–0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63–0.94) and thus not significantly different from 65% (95% CI 0.45–0.85) of the group ≥55 d; (X2(1) = 0.29, p = 0.589).ConclusionsThe results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.

BOLD Coupling between Lesioned and Healthy Brain Is Associated with Glioma Patients' Recovery.

Predicting functional outcomes after surgery and early adjuvant treatment is difficult due to the complex, extended, interlocking brain networks that underpin cognition. The aim of this study was to test glioma functional interactions with the rest of the brain, thereby identifying the risk factors of cognitive recovery or deterioration. Seventeen patients with diffuse non-enhancing glioma (aged 22-56 years) were longitudinally MRI scanned and cognitively assessed before and after surgery and during a 12-month recovery period (55 MRI scans in total after exclusions). We initially found, and then replicated in an independent dataset, that the spatial correlation pattern between regional and global BOLD signals (also known as global signal topography) was associated with tumour occurrence. We then estimated the coupling between the BOLD signal from within the tumour and the signal extracted from different brain tissues. We observed that the normative global signal topography is reorganised in glioma patients during the recovery period. Moreover, we found that the BOLD signal within the tumour and lesioned brain was coupled with the global signal and that this coupling was associated with cognitive recovery. Nevertheless, patients did not show any apparent disruption of functional connectivity within canonical functional networks. Understanding how tumour infiltration and coupling are related to patients' recovery represents a major step forward in prognostic development.

Narrative review of the surgical management of high-risk upper tract urothelial carcinoma

: Upper tract urothelial carcinoma (UTUC) consist of malignancies arising from the urothelium of the collecting system including the renal calyces, renal pelvis down to the level of the distal ureter. High-risk disease consists of any of the following characteristics including (I) the presence of hydronephrosis, (II) tumor size greater than 2 cm, (III) high-grade cytology, (IV) high-grade pathological biopsy, (V) multifocal disease, (VI) previous radical cystectomy for bladder cancer, and (VII) variant histology. The standard surgical management for high-risk disease is radical nephroureterectomy (RNU) with regional lymph node dissection (LND) and bladder cuff excision. This treatment may be performed via an open, laparoscopic, or robotic-assisted laparoscopic approach with varying levels of potential morbidity. Regional LND plays an important prognostic role at the time of RNU in terms of improving staging accuracy for possible early adjuvant therapy. A single instillation of intravesical chemotherapy post-RNU can also help reduce bladder tumor recurrences in the postoperative period regardless of surgical technique. Neoadjuvant or adjuvant chemotherapy can further enhance oncological outcomes with this disease although there is a push toward neoadjuvant therapy due to loss of a renal unit and reduced renal function precluding some patients from adjuvant therapy. Further clinical trials are needed to examine the effects of immunotherapy in the multi-disciplinary treatment of this disease. In the review, we summarize the various surgical treatment options available for high-risk UTUC.

The implications of treatment delays in adjuvant therapy for cholangiocarcinoma patients.

291 Background: To understand the factors associated with timing of adjuvant therapy in the management of intrahepatic and extrahepatic cholangiocarcinoma and the impact of delays on overall survival (OS). Methods: Data from the NCDB for patients with pathologically proven non-metastatic adenocarcinoma of the bile ducts from 2004 to 2014 were pooled and screened. Patients were included only if they underwent surgery and adjuvant chemotherapy (CMT) and/or radiotherapy (RT). Patients who underwent neoadjuvant therapy or received CMT or RT with palliative intent were excluded. Pearson’s chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity-score matching with inverse probability of treatment weighting, OS was compared between patients who had initiation of adjuvant therapy past various time points using Kaplan Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling. Results: In total, 7,422 patients in our analysis underwent adjuvant treatment. This represented 43% of the study cohort of 17,123 patients. Of the patients who underwent adjuvant treatment, 3,956 (53%) initiated adjuvant therapy by two months, 6,234 (84%) by 3 months and 6,987 (94%) by four months. High-grade disease, macroscopically positive margins, tumors larger than five centimeters, and unknown LVSI status, were associated with earlier initiation of adjuvant treatment at two months or earlier. Patients who received early adjuvant therapy were also more likely to be treated with a combination of CMT and RT. Factors associated with delay of adjuvant therapy beyond three months post-surgery included Charlson scores of one or greater and Hispanic race. After propensity score weighting, there was no survival difference between groups when comparing initiation of adjuvant therapy before or after two, three or four month time points Conclusions: We identified a number of patient characteristics related to the timing of initiating adjuvant therapy in patients with biliary cancers. There were no significant difference in OS associated with delaying adjuvant therapy beyond two, three or four month time-points. Our findings are relevant in the era of COVID-19 when minimizing patient exposure to health-care settings during a pandemic may need to be considered when deciding on the timing of adjuvant therapy. If a delay is necessary, our results suggest that there is no survival detriment to initiating adjuvant therapy beyond three or four months after surgery for biliary cancers.

Brivaracetam: How Well Does It Fare as an Anti-Epileptic? A Review.

Epilepsy is a common neurological ailment contributing to significant disability. About one-third of all epilepsy patients would be refractory to two or more medications. Brivaracetam (BRV) is one of the newer anti-seizure medications on which extensive data is available, but its efficacy as an early add-on agent (first/second adjuvant) is unclear. The principal objective of this review is to assess the efficacy of BRV as an early add-on agent in refractory Focal Onset Seizures (FOS) and its pharmacology and usage in various clinical situations associated with seizures. We searched two databases, Medline and Cochrane Central, for papers on BRV and FOS, and selected six studies with randomized parallel control design to extract the data for a meta-analysis. We also did a comprehensive review of the available literature on its pharmacology and usage in various clinical scenarios associated with seizures. For the meta-analysis, we extracted 145 articles; six studies fulfilled the selection criteria that gave us data on 1938 patients who received Brivaracetam as an early add-on agent in FOS. The Risk Ratio (RR) (95% CI) for 50% responders across the trials was 1.88 (1.55-2.29). Similarly, the overall RR (95% CI) was 5.82 (2.15-15.70) for seizure freedom. Our analysis provides moderate evidence for Brivaracetam as an effective agent as an early adjuvant in FOS. Its efficacy for several other indications needs further clinical trials and evaluation.

The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern.

Seminomatous germ cell tumours (SGCT) are the most frequent malignancy in young men. Reliable prognostic biomarkers for the prediction of metastasis at diagnosis and the risk of relapse in clinical stage I (CSI) are lacking. Adjuvant therapies carry a risk of overtreatment, whereas salvage therapies have a risk of high toxicities. Thus, the identification of reliable prognostic biomarkers is highly desirable to identify patients who will benefit from early adjuvant treatment. MicroRNAs (miRNAs) regulate tumour development and progression, and their potential as biomarkers has already been proven in a variety of malignancies. The aim of our study was to define a specific miRNA expression pattern that discriminates metastatic from non-metastatic primary SGCT. Total RNA was isolated from 24 formalin-fixed paraffin-embedded (FFPE) primary SGCT tumours (10 non-metastatic, five metachronously and nine synchronously metastatic) and from 10 normal testicular tissue samples. Microarray analysis was performed for global miRNA expression profiling. The results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed using SPSS. Microarray analyses revealed a specific miRNA pattern that distinguishes metastatic from non-metastatic SGCT. Sixty-three miRNAs were differentially expressed in metastatic compared to non-metastatic tumours (P<.01). Microarray results were confirmed by qRT-PCR for three out of five selected miRNAs (miR-29c-5p, miR-506-3p and miR-371a-5p; P<.05). All five miRNAs (miR-29c-5p, miR-506-3p, miR-1307-5p, miR-371a-5p and miR-371a-3p) showed differential expression between tumour and normal tissues (P<.05). Metastatic primary SGCTs are characterized by a specific miRNA expression pattern. Therefore, specific miRNAs could represent a new tool to predict the metastatic potential in SGCT patients.

Cognitive impairment three months after surgery is an independent predictor of survival time in glioblastoma patients

PurposeCognitive functioning is increasingly investigated for its prognostic value in glioblastoma (GBM) patients, but the association of cognitive status during early adjuvant treatment with survival time is unclear. The aim of this study was to determine whether cognitive performance three months after surgical resection predicted survival time, while using a clinically intuitive time ratio (TR) statistic.MethodsNewly diagnosed patients with GBM undergoing resection between November 2010 and February 2018 completed computerized cognitive assessment 3 months after surgery with the CNS Vital Signs battery (8 measures). The association of cognitive performance (continuous Z scores and dichotomous impairment status; impaired vs. unimpaired) with survival time was assessed with multivariate Accelerated Failure Time (AFT) models that also included clinical prognostic factors and covariates related to cognitive performances.Results114 patients were included in the analyses (median survival time 16.4 months). Of the clinical factors, postoperative Karnofsky Performance Status (TR 1.51), surgical (TR 2.20) and non-surgical (TR 1.94) salvage treatment, and pre-surgical tumor volume (cm3, TR 1.003) were significant independent predictors of survival time. Independently of the base model factors and covariates, impairment on Stroop test I and Stroop test III estimated 23% and 26% reduction of survival time (TR 0.77, TR 0.74) respectively, as compared to unimpaired performance.ConclusionThese findings suggest that impaired performances on tests of executive control and processing speed in the early phase of adjuvant treatment can reflect a worse prognostic outlook rather than an early treatment effect, and their assessment might allow for early refinement of current prognostic stratification.