Multi-institutional Trial Research Articles

A phase II trial of risk enabled therapy after initiating neoadjuvant chemotherapy for bladder cancer (RETAIN BLADDER): Interim analysis.

397 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy (Cx) or chemoradiation (CRT) is the standard of care for urothelial carcinoma (UC) pts with muscle invasive bladder cancer (MIBC). Both Cx and CRT have potential short and long-term toxicity and QOL implications. Mutations in DNA damage repair/response genes are associated with pathologic downstaging after NAC. Methods: We conducted a phase II, multi-institutional clinical trial (NCT02710734) to evaluate a risk-adapted approach to treatment of MIBC. Pts with cT2-T3N0M0 UC of the bladder, ECOG PS 0-1 and CrCl≥50 mL/min, underwent NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC). Pre-NAC TURBT specimens were sequenced (Caris Life Sciences) for mutations (pathogenic or VUS) in ATM, ERCC2, FANCC or RB1. Pts with at least one mutation and no clinical evidence of disease by restaging TUR and imaging post-NAC began pre-defined active surveillance (AS). Remaining pts underwent bladder-directed therapy: intravesical therapy ( < cT2 post-NAC), CRT or Cx. The primary endpoint was metastasis-free survival (MFS) at 2 years which is not mature. We herein report key interim results of clinically-meaningful intermediate endpoints. Results: Seventy-one (ITT) pts were enrolled over 33 months at four academic centers. Median age was 70 years (47-83), 74% were male, 92% Caucasian, 81% ECOG PS 0 and 79% cT2. 90% completed 3 cycles of NAC and with 17% grade 3-4 TRAEs and one death during AMVAC. At the time of data cut-off (September 11, 2020), for the ITT pts, 32 pts have had a Cx, 5 underwent CRT and 7 underwent intravesical therapy, at some point during the trial. Thirty-three pts (46%) had a mutation of interest and 28 pts (39%) started AS (2 of the 28 pts on AS did not have a mutation but elected to start AS after achieving cT0 post AMVAC). 76% of those with a mutation were cT0 at post-NAC TURBT. With a median follow-up of 14.9 mo (range: 3.1-35.3 mo), 14 AS pts recurred (50%). Of the 14 recurrences, 2 recurred with locally advanced or metastatic disease and have died, 5 had MIBC with one eventual metastatic recurrence, and 7 had NMIBC. Six (14%) non-AS pts have died. Out of the 40 pts who did not go to upfront Cx [AS (N = 28), CRT (N = 5), intravesical tx (N = 7)], 3 (7.5%) (all in the AS group) went on to Cx later. The bladder preservation rate is 55% for ITT pts and 89% for the AS group. In the AS cohort, mutations were seen in RB1 (50%), ATM (42%), ERCC2 (31%), FANCC (4%) with lowest rate for recurrence in ERCC2 (25% recurrence) vs RB1 (62% recurrence). Conclusions: Interim results of a phase II trial of risk enabled therapy utilizing a selection of clinical and genomic factors in pts with cT2-T3 MIBC demonstrates a 50% rate of any UC recurrence and a 11% rate of locally advanced/metastatic disease in the AS group. 89% of AS pts have retained their bladder. Follow-up continues for the primary endpoint of 2-year MFS. Clinical trial information: NCT02710734.

Abstract GS2-10: Targeting depressive symptoms in younger breast cancer survivors: A randomized controlled trial of mindfulness meditation and survivorship education

Abstract Purpose Breast cancer before age 50 comprises 25% of incident breast cancer cases in women. Younger breast cancer survivors (YBCS) are at increased risk for the negative effects of cancer diagnosis and treatment, including elevated levels of depression and related symptoms (i.e., anxiety, stress, fatigue, sleep disturbance, vasomotor symptoms), leading to significantly diminished quality of life. Patients and Methods This Phase III, randomized, multi-institution trial was designed to examine the efficacy of two brief interventions- mindfulness meditation and survivorship education - for YBCS (ClinicalTrials.gov NCT03025139). We recruited women diagnosed at age 50 or younger with early-stage breast cancer who had completed cancer treatment between 6 months and 5 years earlier and endorsed at least mild depressive symptoms. Participants were randomly assigned to Mindful Awareness Practices (MAPs), Survivorship Education (SE), or wait-list control (WL). Both intervention programs were tailored for YBCS and included 6 weeks of structured content delivered in a group format. Assessments were conducted at baseline, post-intervention, and at 3- and 6- month post-intervention follow-ups. The primary outcome was depressive symptoms (Center for Epidemiologic Studies Depression scale; CESD) at post-intervention; secondary outcomes included anxiety (Generalized Anxiety Disorder-7), fatigue severity (Fatigue Symptom Inventory), sleep disturbance (Insomnia Severity Index), and hot flashes (BCPT symptom checklist). Results We enrolled and randomized 247 women (85 MAPS, 81 SE, 81 WL). On average, participants were 45.4 years old at study entry and had been diagnosed 2.6 years earlier. Linear mixed models were conducted to compare each intervention group to WL on primary and secondary outcomes, controlling for baseline differences across groups in study site, race, and marital status. MAPs led to significant reductions in depressive symptoms at post-intervention and at 3- and 6-month follow-up relative to WL (Ps < .01); see Table 1. SE also led to significant reductions in the CESD at post-intervention and 3-month follow-up (Ps < .01). Both MAPs and SE produced reductions in anxiety at post-intervention relative to WL (Ps < .05), though effects did not persist over follow-up. MAPs also had beneficial effects on other secondary outcomes, yielding significant decreases in fatigue severity, sleep disturbance, and hot flashes that persisted over the 6-month follow-up (Ps < .05). In contrast, there was minimal evidence that SE impacted these outcomes. Conclusion Two brief behavioral intervention programs specially designed for YBCS were effective in reducing depressive symptoms and, in the case of mindfulness, improving related symptoms (fatigue, sleep disturbance) that pose serious threats to younger women’s health and well-being after cancer. These interventions are standardized, manualized, and have the potential for wide dissemination over virtual platforms. Table 1 Adjusted means and standard error (SE) for CESD depressive symptoms by group and time, controlling for study site, race, marital status. A CESD score of 16 or greater indicates moderately severe depressive symptoms. P-values are for differences between intervention and waitlist control groups in change over time between Baseline and Post-Intervention (1-2), Baseline to 3-month Follow-up (1-3), and Baseline to 6-month Follow-up (P 1-4). BaselinePost-intvP (1-2)3 mo FUP (1-3)6 mo FUP (1-4)GroupCESDCESDCESDPCESDMindful Awareness Practices (MAPs)18.4 (1.0)13.6 (1.1).00113.4 (1.1)<.00112.9 (1.1).013Survivorship Education (SE)17.4 (1.1)13.3 (1.1).00713.6 (1.2).00312.7 (1.2).063Waitlist (WL)16.5 (1.1)16.3 (1.1)17.3 (1.2)14.6 (1.1) Citation Format: Patty Ganz, Julienne E Bower, Ann H Partridge, Antonio C Wolff, Elissa D Thorner, Hadine Joffe, Michael R Irwin, Laura Petersen, Laura Petersen, Catherine M Crespi. Targeting depressive symptoms in younger breast cancer survivors: A randomized controlled trial of mindfulness meditation and survivorship education [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-10.

Abstract PS1-43: Axillary surgery after neoadjuvant chemotherapy in patients treated for an operable breast cancer with a proven initially positive axillary node: Preliminary results of identification and removal of the initially positive axillary node

Abstract BackgroundAlmost half of the patient with initially metastatic axillary node, treated with neoadjuvantchemotherapy (NAC) for a large operable breast cancer, has no axillary lymph node involvementat the time of surgery after NAC. Sentinel lymph node detection (SLND), performed after NAC,has a high false negative rate (FNR) when compared to FNR after primary surgery. GANEA 3 isa French prospective multi institutional ongoing trial, aimed at assessing the impact of targeting,before NAC, the initially positive node and removing it after NAC. The main objective of GANEA3 trial is the accuracy of this initially positive node to predict pathological status of the otheraxillary nodes after NAC. A total of 385 patients are required.ObjectiveThe current abstract assessed preliminary results of the detection rate of the clipped node and thedifferent methods to find it during axillary surgery based on the first 41 patients.Patients and MethodThis study is part of GANEA 3 Trial validated by scientific national board (clinicialtrials.gov:NCT03630913).Inclusion criteria: TNM stage T1-T3 N1 infiltrating breast carcinoma, indication of NAC, andsigned consent form,Exclusion criteria: more than 5 suspicious axillary nodes, inflammatory cancer, local relapse,mental disorder, pregnancy or no contraceptive method, contra-indication to NAC, NACinterrupted due to progressive disease.Design: Patients treated for an early breast cancer with NAC, axillary sonography with fine needlecytology before NAC to select patients with a proven lymph node involvement. Initially positive node identification warranted, for example with a clip. After NAC patients underwent the removalof the clipped node, a SLN detection with the combined method (patent blue and technetium) andan axillary lymph node dissection (ALND). In order to find the clipped node, during surgery thesurgeon attempted to find it with palpation and sonography. Each surgical specimen was then x-rayed before pathological examination.Studied parameters were clipped node and SLND detection rate, and the methods used to find theclipped node.ResultsFrom January 2019, to November 2019, 41 patients were enrolled, from 13 institutions, withinitially positive axillary node clipped, NAC courses and surgery after NAC.Median age was 53 (31-75), pathological subtype infiltrative ductal carcinoma (n=40) andinfiltrative lobular carcinoma (n=1), a median of 7 courses of NAC (1-16).SLN detection rate was 90% (37/41). A median number of 2 sentinel nodes were removed (1-7).The clipped node was removed in 100% of cases. The clipped node was identified by thesurgeon palpation (n=11), an axillary wire (n=13), per operative axillary sonography (n=4),surgical specimen radiography (n=11), the pathologist (n=2).The clipped node was part of SLN in 29 cases (70%). It was part of axillary lymphadenectomyspecimen in 6 cases (14.5%) and was find alone as an isolated node in 6 cases (14.5%).ConclusionThe clipped node was always found after NAC. It was mostly always part of SLN or ALNDspecimens. Further studies are needed in order to help the surgeon to remove only the clippednode. Citation Format: Celine Renaudeau, Roman Rouzier, Pierre Gimbergues, Marian Gutowski, Eva Jouve, Philippe Rauch, Charles Coutant, Christelle Faure, Catherine Uzan, Pierre-François Dupré, Vivien Ceccato, Charlotte N'go, Augustin Reynard, Isabelle Doutriaux, Loic Campion, Jean-Marc Classe. Axillary surgery after neoadjuvant chemotherapy in patients treated for an operable breast cancer with a proven initially positive axillary node: Preliminary results of identification and removal of the initially positive axillary node [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-43.

Abstract PS2-41: Supplemental contrast enhanced mammography screening of women with elevated risk of breast cancer

Abstract Objective and Rationale: To investigate the utility of screening Contrast Enhanced Mammography (CEM) imaging as a supplemental screening tool in women at elevated risk for breast cancer. Materials and Methods: This prospective, single institution, IRB approved observational study was conducted in asymptomatic women 35 years of age or older who were deemed at elevated risk of breast cancer, defined as IBIS v.8.0 lifetime risk of breast cancer score >15% or a prior personal history of breast cancer. Enrollment started in January 2019 and is on-going. An interim data analysis was performed. Women were invited to undergo supplemental CEM screening within 180 days of negative (BI-RADS 1 or 2) conventional 2D/3D screening mammography (MG). Patients with prior screening MBI, ultrasound or MR imaging within 12 months were excluded from study participation. Outcome measures were supplemental cancer detection rates, sensitivity, specificity, positive predictive value, and negative predictive value of CEM, along with their 95% confidence intervals, as well as the biologic profiles of MG-occult, CEM detected cancers. Results: A total of 351 women were enrolled in this prospective study over a 20-month period. To date, we have 1 year follow up on 106 cases with negative follow-up MG. Average age of the participants was 56 years ± 9.44 (standard deviation); 11 patients had screening 2D MG, 333 had combined 3-D and 2-D screening MG; 309 dense and 37 non-dense breasts based on ACR BI-RADS categories. CEM depicted 8 additional breast cancers (table 1), which were otherwise MG occult, for an overall supplemental cancer detection rate of 22.7 per 1000 patients, 95% CI (9.9, 44.3). 1 false negative cancer on CEM imaging which was further detected on MR imaging only. Biopsy revealed 16 benign changes (16/28=57%), 4 high-risk lesions (4/28=14%), and 8 breast cancers (8/28=29%) (table 2). CEM imaging screening offered high specificity (0.942, 95% CI (0.917, 0.967), high NPV 0.997, 95% CI (0.991, 1.000) and moderate PPV (0.286, 95% CI (0.118, 0.453) and sensitivity (0.889, 95% CI (0.684, 1.000)). Size of CEM detected cancers ranged from 7 to 57 mm. Conclusion: This pilot trial demonstrates a supplemental cancer detection rate of 22.7 per 1000 during prevalence round of CEM screening in women at an elevated risk for breast cancer. These initial results are comparable to results reported for high-risk surveillance MR imaging. Larger, multi-institutional high-risk CEM trials are needed for those patients who are not otherwise undergoing regular supplemental surveillance MR imaging. Citation Format: Bhavika K. Patel, Victor Pizzitola, Donald Northfelt, Karen Anderson, Marina Giurescu, Gina Mazza, Roxanne Lorans, William Eversman, Richard Sharpe, Juliana Kling, Denise Millstine, Ernst Brenda, Patricia Cronin, Heidi Apsey, Jennifer Palmieri, Barbara Pockaj, Michele Halyard. Supplemental contrast enhanced mammography screening of women with elevated risk of breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-41.

Abstract PD4-05: Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study

Abstract Background: Four prospective multi-institutional trials have demonstrated that clinically node-positive patients (cN1) who receive neoadjuvant therapy (NAC) and convert to cN0 can be reliably staged with sentinel lymph node biopsy (SLNB) with false-negative rates (FNRs) of < 10%, when ≥ 3 SLNs are retrieved. Since study patients all had axillary lymph node dissection (ALND), the rate of axillary recurrence after SLNB alone is unknown. Of concern is the possibility that residual chemotherapy-resistant axillary disease could lead to higher recurrence rates than seen in the primary surgery setting for cN0 patients where SLN FNRs of 5-10% result in axillary recurrence in < 1% of cases. Here we report regional recurrence rates in a prospectively defined cohort of cN1 patients receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. Methods: From 06/2014 to 02/2019, patients with cT1-3 biopsy-proven cN1 breast cancer who received NAC and converted to cN0 by physical exam were prospectively managed with SLNB with dual tracer mapping and omission of ALND if ≥ 3 SLNs were pathologically negative. Nodes were not routinely clipped, and retrieval of clipped metastatic nodes was not required. Pathologically negative SLNs were defined as the absence of any metastases including isolated tumor cells. Results: Of 610 cN1 patients treated with NAC, 555 (91%) converted to cN0 and had SLNB; 234 (42%) had ≥ 3 negative SLNs and were treated with SLNB alone. Median patient age was 49 years and median tumor size at presentation was 3 cm; 61% were HER2+ and 18% triple negative. Most (91%) received doxorubicin-based NAC and 88% received adjuvant radiotherapy (RT), with 80% (n = 164) of RT patients receiving nodal RT (Table). At a median follow-up of 35 months, there was only 1 (0.4%) axillary recurrence for the entire cohort, synchronous with a breast recurrence, in a patient who refused RT. Among patients who received RT (n = 205), there were no axillary recurrences. The 4-year rate of distant recurrence for all patients was 6.1% (95% CI, 3.4-10.7%) and 4-year overall survival was 93.9% (95% CI, 87.6-97.1%). Conclusion: In cN1 patients treated with NAC, rates of axillary recurrence in patients with ≥ 3 pathologically negative SLNs treated with SLNB alone were low, without routine nodal clipping. Although further follow-up is needed, multiple studies have shown that nodal recurrence is an early event, particularly in HER2+ and triple negative patients, who comprised the majority of the population. Our findings support omitting ALND in cN1 patients after NAC when the SLNs are negative using an optimal SLNB technique. Table. Patient PopulationOverall cohort (n = 234)Age, years (median, IQR)49 (40, 58)Tumor size at presentation, cm (median, IQR)3.0 (2.2, 5.0)Number SLNs retrieved (median, IQR)4 (3, 5)Palpable nodes at presentation (n, %)179 (76%)HistologyDuctal211 (90%)Lobular and mixed7 (3%)Micropapillary and mixed10 (4%)Other3 (1%)Occult3 (1%)DifferentiationWell1 (0.5%)Moderate36 (15%)Poor196 (84%)Unknown1 (0.5%)Receptor StatusHR+/HER2-47 (20%)HR+/HER2+80 (34%)HR-/HER2+64 (27%)HR-/HER2-43 (18%)Breast SurgeryBCS118 (50%)Mastectomy116 (50%)Breast pCR¥Yes161 (70%)No70 (30%)NAC regimenAC-T197 (84%)AC-T + carbo15 (6.4%)TC8 (3.4%)Other14 (6%)Neoadjuvant anti-HER2 treatmentHP (dual-therapy)144 (100%)Adjuvant RTYes205 (88%)No*29 (12%)¥3 patients had occult primary breast cancer and were not included in breast pCR calculation; *6/29 patients who did not receive RT enrolled in NSABP B-51 Citation Format: Andrea V Barrio, Giacomo Montagna, Anita Mamtani, Varadan Sevilimedu, Hiram S Cody, III, Mahmoud El-Tamer, Mary L Gemignani, Alexandra S Heerdt, Tracy-Ann Moo, Melissa Pilewskie, George Plitas, Lisa Sclafani, Kimberly J Van Zee, Monica Morrow. Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-05.

Light Chain-Predominant Multiple Myeloma Subgroup; Impaired Renal Function Correlates with Decreased Survival in this Subgroup

Background: Patients with light chain-predominant multiple myeloma have been shown to exhibit shorter survival. Retrospective comparison of clinical and laboratory data was undertaken to ascertain the likely cause(s) of this observation. Methods: Records of multiple myeloma patients seen at one institution revealed 316 cases of conventional and 71 cases of light chain-predominant multiple myelomas with secretion of intact immunoglobulins. Laboratory and clinical findings in the two groups were compared. Findings: Patients with light chain-predominant multiple myeloma had a significantly higher death rate, higher rate of chronic dialysis, and a lower eGFR and serum albumin, a significantly higher urine protein concentration, and a significantly higher prevalence of hypertension and blood transfusion requirements. Other clinical and laboratory parameters surveyed were not significantly different between the two groups. Interpretation: The shorter survival of patients with light chain-predominant multiple myeloma is likely to be due to renal damage caused by the excess free immunoglobulin light chains. Renal damage might be ameliorated by early aggressive treatment with chemotherapy, plasmapheresis and dialysis; a multi-institutional prospective controlled trial would be needed to test this hypothesis. Funding Statement: None to declare. Declaration of Interests: Dr. Singh serves as a consultant to Diazyme Inc. and HealthTap. All other authors have nothing to declare. Ethics Approval Statement: The study protocol was reviewed and approved by the institutional review board.

Feasibility of an Updated Randomised Controlled Trial on Surgical Urolithiasis Treatments: The Pilot Trial for the German Endoscopic versus Shock Wave Therapy Study (GESS)

Data comparing treatments for urolithiasis are often outdated, with inconsistent results or poor methodological and reporting quality. We report a pilot study in preparation for a larger multicentre randomised controlled trial (RCT) comparing shockwave therapy and ureteroscopy in patients with a single urinary stone of ≤20 mm in the upper urinary tract. Primary objectives included screening completeness, patients’ willingness to participate, their remaining in the study, the suitability of the eligibility criteria, and the acceptability of the outcome measures. Screened individuals not invited to participate were those with no indication for active treatment among referred patients (n = 166), those who staff failed to screen (n = 99), and patients not meeting the inclusion criterion of a single stone (n = 422). Of the 176 patients invited, 116 refused to participate. Ultimately, we were able to recruit 60 patients within 34 mo. All patients underwent their allocated treatments. This pilot trial provides an in-depth analysis of the feasibility of an RCT on surgical treatments for upper urinary tract urolithiasis in a highly regulated health care system. The study procedures and outcome measures proved acceptable and feasible. On the basis of these data, we propose a pragmatic, multicentre RCT to deliver updated, high-level evidence on the efficacy of currently available treatments for urolithiasis. Patient summaryWe performed a small pilot trial comparing current treatments in urolithiasis. We were able to prove the feasibility of a larger multi-institutional trial with regard to the time needed to recruit an adequate number of patients and the acceptability of the treatments and outcome measures.

Deep learning magnetic resonance spectroscopy fingerprints of brain tumours using quantum mechanically synthesised data

Metabolic fingerprints are valuable biomarkers for diseases that are associated with metabolic disorders. 1H magnetic resonance spectroscopy (MRS) is a unique noninvasive diagnostic tool that can depict the metabolic fingerprint based solely on the proton signal of different molecules present in the tissue. However, its performance is severely hindered by low SNR, field inhomogeneities and overlapping spectra of metabolites, which affect the quantification of metabolites. Consequently, MRS is rarely included in routine clinical protocols and has not been proven in multi-institutional trials. This work proposes an alternative approach, where instead of quantifying metabolites' concentration, deep learning (DL) is used to model the complex nonlinear relationship between diseases and their spectroscopic metabolic fingerprint (pattern). DL requires large training datasets, acquired (ideally) with the same protocol/scanner, which are very rarely available. To overcome this limitation, a novel method is proposed that can quantum mechanically synthesise MRS data for any scanner/acquisition protocol. The proposed methodology is applied to the challenging clinical problem of differentiating metastasis from glioblastoma brain tumours on data acquired across multiple institutions. DL algorithms were trained on the augmented synthetic spectra and tested on two independent datasets acquired by different scanners, achieving a receiver operating characteristic area under the curve of up to 0.96 and 0.97, respectively.

Case series of elderly patients with scabies topically applied with ivermectin via whole-body bathing.

As a novel method of ivermectin (IVM) administration for the treatment of scabies, we devised a whole-body bathing (WBB), in which patients are immersed in a fluid that contains IVM. A multi-institutional trial for elderly patients with scabies was conducted to investigate the efficacy and safety of IVM-WBB. Seven elderly patients with scabies were enrolled and received IVM-WBB up to four times at 1-week interval. The cure for scabies was defined as the absence of mites in two consecutive microscopic or dermoscopic examinations at weekly intervals and the absence of new skin lesions indicative of scabies. Consequently, the cure rate on day 22, the primary end-point, was 71.4%, and all patients had been cured until day 29. Additionally, neither significant adverse events nor clinically problematic abnormal blood test values were obtained. Furthermore, no IVM was detected in the optional plasma (five cases) collected for IVM measurement after bathing. These results suggest that IVM-WBB was effective to treat scabies, causing no serious adverse events and with a very low internal exposure of IVM.

Comparison of Hernia Recurrence and Seroma Formation in Cancer Patients Undergoing Incisional Hernia Repair with Transfascial Sutures vs. Fibrin Glue for Mesh Fixation

Background: Open ventral incisional hernia repairs with mesh reduce hernia recurrence rates to less than 10%. The Rives-Stoppa retrorectus hernia repair technique is becoming the standard of care for mesh repair of complex incisional hernias. In these hernia repairs, mesh has traditionally been fixated with transfascial sutures, but fibrin glue has been used as an alternative to reduce pain and may also reduce operative time and the risk of seroma formation. The primary objective of this study was to compare the rates of hernia recurrence and seroma formation in cancer patients who underwent Rives-Stoppa incisional hernia repair using transfascial sutures vs. fibrin glue for mesh fixation. Methods: We conducted a retrospective review of a prospectively maintained database of cancer patients at our free-standing cancer institution who underwent Rives-Stoppa ventral incisional hernia repair performed at our institution. Fisher’s exact test was used to assess differences in hernia recurrence and seroma formation rates between patients who underwent mesh fixation with transfascial sutures vs. fibrin glue. Using a neutral prior probability distribution, a Bayesian analysis was performed to evaluate the posterior probability of seroma formation requiring intervention and hernia recurrence after retrorectus repair with fibrin glue fixation. Log-rank test was used to assess the difference in overall survival between the two groups. Results: Forty-one patients (22 in the transfascial suture group and 19 in the fibrin glue group) were included in the analysis. The patient demographics were similar in both groups. There was no statistically significant difference in seroma formation requiring drainage by interventional radiology (IR) between the fibrin glue and the transfascial suture groups (5.3% vs. 9.1%; P=1.00). The odds of having a hernia recurrence was 4 times higher in the transfascial suture group than in the fibrin glue fixation group, but this was not statistically significant (18.2% vs 5.3%, p=0.35). The Bayesian analysis showed a 90% probability that the hernia recurrence rate would be higher in the transfascial suture than in the fibrin glue fixation group. Conclusion: Using fibrin glue instead of transfascial sutures may reduce hernia recurrences and seroma formation in cancer patients undergoing ventral incisional hernia repairs with retro rectus mesh. The high probability of reducing the odds of hernia recurrence with fibrin glue fixation warrants a prospective randomized, multi-institutional clinical trial.

Treatment Options for Leptomeningeal Metastases of Solid Cancers: Literature Review and Personal Experience.

Leptomeningeal metastases (LM) may complicate the clinical course of any solid cancer or hematological malignancy. Diagnosis of such cases requires a multifaceted approach, including careful evaluation of the clinical history, detailed neurological examination, advanced imaging studies, and related laboratory data analysis. Therapeutic options for management of LM have not been standardized yet. Conventional intrathecal chemotherapy with or without involved-field fractionated radiotherapy has only modest efficacy, and the prognosis of most patients remains grim. Therefore, development of new, more aggressive multimodal treatment strategies is definitely needed. Immune checkpoint inhibitors-in particular, molecular targeted therapy-have demonstrated promising results in selected groups of patients. There may be an important role for stereotactic radiosurgery as well. Because organization of prospective randomized multi-institutional trials on treatment of LM of solid cancers may be problematic, practical guidelines for optimal therapeutic strategies in such cases should be established on the basis of integrated results of small-scale prospective and retrospective studies.

Progress in Multimodal Treatment for Advanced Esophageal Squamous Cell Carcinoma: Results of Multi-Institutional Trials Conducted in Japan.

Simple SummaryIn Japan, the therapeutic strategies for esophageal squamous cell carcinoma (ESCC) are based on the results of multi-institutional trials conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Since there are several differences in the factors influencing the treatment approach for esophageal cancer between Eastern and Western countries, the therapeutic strategies adopted in Asian countries, especially Japan, are often different from those in Western countries. Because a transthoracic esophagectomy with three-field lymph node dissection has been performed as a standard surgical procedure for advanced thoracic ESCC in Japan, multimodal treatment for ESCC has been developed to improve the surgical outcomes after this relatively invasive surgical procedure. In this review, we describe the history and current status of therapeutic strategies for ESCC in Japan with a focus on the results of clinical trials conducted by the JEOG.In Japan, the therapeutic strategies adopted for esophageal carcinoma are based on the results of multi-institutional trials conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Owing to the differences in the proportion of patients with squamous cell carcinoma among all patients with esophageal carcinoma, chemotherapeutic drugs available, and surgical procedures employed, the therapeutic strategies adopted in Asian countries, especially Japan, are often different from those in Western countries. The emphasis in respect of postoperative adjuvant therapy for patients with advanced esophageal squamous cell carcinoma (ESCC) shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy in the 1990s. In the 2000s, the optimal timing of administration of perioperative adjuvant chemotherapy returned from the postoperative adjuvant setting to the preoperative neoadjuvant setting. Recently, the JEOG commenced a three-arm randomized controlled trial of neoadjuvant therapies (cisplatin + 5-fluorouracil (CF) vs. CF + docetaxel (DCF) vs. CF + radiation therapy (41.4 Gy) (CRT)) for localized advanced ESCC, and patient recruitment has been completed. Salvage and conversion surgeries for ESCC have been developed in Japan, and the JEOG has conducted phase I/II trials to confirm the feasibility and safety of such aggressive surgeries. At present, the JEOG is conducting several trials for patients with resectable and unresectable ESCC, according to the tumor stage. Herein, we present a review of the JEOG trials conducted for advanced ESCC.

Remote monitoring and treatment of children and adolescents with type 1 diabetes

Continuous subcutaneous insulin infusion (CSII) is an effective method for optimizing glycemic control in children with type 1 diabetes mellitus (DM1). However, the use of CSII does not always result in adequate glycemic control. Telehealth can be applied as one of the methods to improve the effectiveness of treatment. To evaluate the use of remote medical support of children and adolescents with DM1 and its influence on glycemic control, quality of life, and incidence of acute complications of DM1. We conducted a 24-week multi-institutional prospective open-label controlled clinical trial. 180 children and adolescents were included in this study and divided into the following categories: 1) age 8-18 years; 2) DM1 at least 1 year; 3) pump insulin therapy Medtronic Paradigm (Medtronic MiniMed, USA) at least 6 months; 4) self-monitoring of glycemia at least 4 times a day and replacement of the insulin pump infusion system at least once every 3 days; 5) inadequate glycemic control of DM1: the level of glycated hemoglobin (HbA1c) 7.5% or higher. Patients were assigned to a remote consultation group (RC; n=100) or a traditional control group (TC; n=80). All patients were trained on the basic principles of DM1 and CSII, and we measured initial HbA1c, then after 12 and 24 weeks, also registered and analyzed glycemic indicators and daily doses of insulin, evaluated and corrected the treatment. Patients or their parents in the RC group sent pump data via the Internet to the pump insulin therapy center at least once every 2 weeks at home and received treatment recommendations in response. The total number of patients included in the study in all institutions was 180 children at 8-18 years. Patients in both groups did not differ in age, gender, duration of DM1 and CSII, and HbA1c level. The total amount of remote consultations for all institutions was 949. The decrease in the level of HbA1c by the end of the study against the initial one was statistically significantly greater in the RC group: 1.17% compared to 0.59% in the TC group (p<0.05). The proportion of patients who reached the target level of HbA1c (<7.5%) was significantly higher in the RC group (32%) compared to the TC group (12.5%, p<0.05). During the study, the incidence of DKA and severe hypoglycemia in the RC group was statistically significantly lower. Remote monitoring in children with DM1 resulted in significant improvements in glycemic control (HbA1c, glycemic variability, and hypoglycemic frequency). The accumulation of evidence on the effectiveness and safety of telehealth in DM should contribute to implementing this approach in practical health care.

The effects of sample handling on proteomics assessed by reverse phase protein arrays (RPPA): Functional proteomic profiling in leukemia

Reverse phase protein arrays (RPPA) can assess protein expression and activation states in large numbers of samples (n > 1000) and evidence suggests feasibility in the setting of multi-institution clinical trials. Despite evidence in solid tumors, little is known about protein stability in leukemia. Proteins collected from leukemia cells in blood and bone marrow biopsies must be sufficiently stable for analysis. Using 58 leukemia samples, we initially assessed protein/phospho-protein integrity for the following preanalytical variables: 1) shipping vs local processing, 2) temperature (4 °C vs ambient temperature), 3) collection tube type (heparin vs Cell Save (CS) preservation tubes), 4) treatment effect (pre- vs post-chemotherapy) and 5) transit time. Next, we assessed 1515 samples from the Children's Oncology Group Phase 3 AML clinical trial (AAML1031, NCT01371981) for the effects of transit time and tube type. Protein expression from shipped blood samples was stable if processed in ≤72 h. While protein expression in pre-chemotherapy samples was stable in both heparin and CS tubes, post-chemotherapy samples were stable in only CS tubes. RPPA protein extremes is a successful quality control measure to identify and exclude poor quality samples. These data demonstrate that a majority of shipped proteins can be accurately assessed using RPPA. SignificanceRPPA can assess protein abundance and activation states in large numbers of samples using small amounts of material, making this method ideal for use in multi-institution clinical trials. However, there is little known about the effect of preanalytical handling variables on protein stability and the integrity of protein concentrations after sample collection and shipping. In this study, we used RPPA to assess preanalytical variables that could potentially affect protein concentrations. We found that the preanalytical variables of shipping, transit time, and temperature had minimal effects on RPPA protein concentration distributions in peripheral blood and bone marrow, demonstrating that these preanalytical variables could be successfully managed in a multi-site clinical trial setting.

Prospective Evaluation of the Transparent, Elastomeric, Adaptable, Long-Lasting (TEAL) Respirator.

N95 filtering facepiece respirators (FFR) and surgical masks are essential in reducing airborne disease transmission, particularly during the COVID-19 pandemic. However, currently available FFR’s and masks have major limitations, including masking facial features, waste, and integrity after decontamination. In a multi-institutional trial, we evaluated a transparent, elastomeric, adaptable, long-lasting (TEAL) respirator to evaluate success of qualitative fit test with user experience and biometric evaluation of temperature, respiratory rate, and fit of respirator using a novel sensor. There was a 100% successful fit test among participants, with feedback demonstrating excellent or good fit (90% of participants), breathability (77.5%), and filter exchange (95%). Biometric testing demonstrated significant differences between exhalation and inhalation pressures among a poorly fitting respirator, well-fitting respirator, and the occlusion of one filter of the respirator. We have designed and evaluated a transparent elastomeric respirator and a novel biometric feedback system that could be implemented in the hospital setting.

Long-Term Results of NRG Oncology/RTOG 0321: A Phase II Trial of Combined High Dose Rate Brachytherapy and External Beam Radiation Therapy for Adenocarcinoma of the Prostate

To report the long-term outcome of patients with prostate cancer treated with external beam radiation therapy and high dose rate (HDR) brachytherapy from a prospective multi-institutional trial conducted by NRG Oncology/RTOG. Patients with clinically localized (T1c-T3b) prostate cancer without prior history of transurethral resection of prostate or hip prosthesis were eligible for this study. All patients were treated with a combination of 45 Gy in 25 fractions from external beam radiation therapy and one HDR implant delivering 19 Gy in 2 fractions. Adverse events (AE) were collected using Common Toxicity Criteria for Adverse Events, version 3. Cumulative incidence was used to estimate time to severe late gastrointestinal (GI)/genitourinary (GU) toxicity, biochemical failure, disease-specific mortality, local failure, and distant failure. Overall survival was estimated using the Kaplan-Meier method. One hundred and twenty-nine patients were enrolled from July 2004 to May 2006. AE data was available for 115 patients. Patients were National Comprehensive Cancer Network (NCCN) intermediate to very high risk. The median age was 68, T1c-T2c 91%, T3a-T3b 9%, PSA ≤10 70%, PSA >10 to ≤20 30%, GS 6 10%, GS 7 72%, and GS 8 to 10 18%. Forty-three percent of patients received hormonal therapy. At a median follow-up time of 10 years, there were 6 (5%) patients with grade 3 GI and GU treatment-related AEs, and no late grade 4 to 5 GI and GU AEs. At 5 and 10 years, the rate of late grade 3gastrointestinal and genitourinary AEs was 4% and 5%, respectively. Five- and 10-year overall survival rates were 95% and 76%. Biochemical failure rates per Phoenix definition at 5 and 10 years were 14% and 23%. The 10-year rate of disease-specific mortality was 6%. At 5 and 10 years, the rates of distant failure were 4% and 8%, respectively. The rates of local failure at 5 and 10 years were 2% at both time points. Combined modality treatment using HDR prostate brachytherapy leads to excellent long-term clinical outcomes in this prospective multi-institutional trial.

Total Neoadjuvant Therapy for Rectal Cancer: Current Status and Future Directions

The investigation of total neoadjuvant therapy has increased significantly in recent years, with a number of approaches being utilized in ongoing prospective studies, including (1) induction neoadjuvant chemotherapy (INCT), (2) consolidation neoadjuvant chemotherapy (CNCT), and (3) short-course radiation therapy (SC-RT) for locally advanced rectal cancer (LARC). Significant questions remain regarding the ideal sequence of a total neoadjuvant therapy (TNT) approach. Multiple prospective multi-institutional trials have evaluated the addition of multi-agent chemotherapy before or after neoadjuvant rectal cancer chemoradiation. In 2019, a multi-center randomized phase II trial from Germany, CAO/ARO/AIO-12, demonstrated better compliance and lower toxicities with CNCT in comparison to INCT. The OPRA study recently reported in ASCO 2020 improved organ preservation for CNCT, and similar 3-year disease-free survival (DFS) and distant metastasis-free survival (DMFS). RAPIDO reports higher rates of pathologic complete response (pCR) and lower rates of 3-year distant metastases (DM) for TNT compared to traditional treatment sequencing. Recent literature on TNT for LARC highlights the potential of this approach to enhance compliance, increase distant control and survival rates, and reduce toxicities. Further research is important to tailor treatment approaches to patients with LARC.

Factors Predictive of Oral Abstract Being Published: Is Gender Disparity Playing a Role?

Introduction: It remains unclear what percentage of abstracts proceed to manuscript publication and the characteristics that predict successful publication. This study aimed to determine factors associated with successful peer-reviewed publications following oral presentation at the American Society of Hematology (ASH) annual meeting. Methods: All oral abstract presentations (n=621) in the hematological malignancy category from 2016 ASH annual meeting were included in the study. Abstract publication was confirmed by searching for the publicly listed abstract on PubMed by title, first, and last author names, and institutional matching. We recorded time to online publication, US versus foreign journal publication, and journal impact factor by 3.5 years from 2016 ASH annual meeting. Abstracts characteristics that were analyzed also included number of authors, gender of first author, gender of last author, and single vs multi-institution studies. Gender of the first and last author was confirmed by looking at their biography details on their institutional website. Descriptive analysis was performed and an association between presenter's or last author's gender and publication matrix was analyzed using Chi-square tests. Results: Of the 621 abstracts, 350 (56%) were published in full text by three and a half years since the 2016 ASH annual meeting. The abstracts' average time to journal publication was 17.46 months (SD +/- 11.32) (Table 1). Of the published articles, 64% (223/350) were published in U.S. journals; mean impact factor for all publications was 14.46 (SD+/- 11.47).The median number of authors for published and unpublished abstracts were similar. Females presented 37% (228/621) of the abstracts and 35% (123/350) of the journal publications had female first author and 22% (77/350) had female last author. A total of 53.9% (123/228) abstracts presented by a female author were published versus 57.7% (227/393) abstracts presented by a male author (p=<0.001). Males were more often involved in multi-institutional trials (p=0.045) and were more likely to have senior authorship (p=0.005). There was no correlation between the gender of the first author to journal impact factor (p=0.109) or time to publication (p=0.091). Conclusion: More than half of the oral abstracts were successfully published regardless of gender and number of authors. The rate of successful publication is higher for male authors even though there was no correlation between the gender of the first author to journal impact factor or time to publication. Our study highlights gender disparity in senior authorship, however this difference is not as wide in first authorship. Disclosures Jamshed: Takeda, Amgen and Celgene: Honoraria.

Outcomes of Front-Line Therapy for Adult T Cell Leukemia/Lymphoma: A Pooled Analysis of Two Institutions

Introduction: Adult T cell leukemia/lymphoma (ATLL) is an aggressive mature T cell neoplasm caused by Human T lymphotropic virus type 1/2 (HTLV1/2) infection. HTLV1/2 is endemic in several geographic areas such as Latin America, Japan and intertropical Africa with estimated 5-10 million individuals infected worldwide. There is no standard therapy for ATLL and most patients are treated with regimens used for aggressive lymphomas. We hereby reviewed the outcome of patients treated in two US academic medical centers with a high prevalence of ATLL. Methods: We retrospectively evaluated all of the patients with a confirmed diagnosis of ATLL seen in two academic medical centers in Florida, USA. Baseline characteristics, treatments regimens and clinical outcomes where evaluated. First line therapies were categorized as treatment with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), Intensive chemotherapy (HyperCVAD, VCAP-AMP-VECP, or EPOCH), vs others (Interferon and zidovudine, Gemcitabine Oxaliplatin, Pralatrexate, and Gemcitabine cisplatin dexamethasone). Patient and disease characteristics were compared using Chi-square. Progression free survival (PFS) and overall survival (OS) for different chemotherapy regimens were compared using log-rank testing. Results A total of 61 patients were included in the analysis. The median age was 58 (32-75) years. Two thirds of the patients were female. The majority were of African American descent (82.5%) (Table 1), and 35.6% were originally from Jamaica, followed by 13.6% from Haiti. Patients were more likely to have CR/PR to CHOP (72%) compared to those treated with intensive chemotherapy or others (27.3% and 29.4% respectively) (p=0.007) (figure 1A). While there was no statistically difference in baseline characteristics in patients receiving the three categories of treatments (i.e. age, stage, ECOG, CD30 status), patients with acute subtype were less likely to be treated with CHOP (21.1% vs 47.4% respectively, p=0.096) which might explain the discrepancies in response. There was no statistical difference in PFS and OS between the three CHOP, Intensive chemotherapy and others (6.4 mo, 3.1 mo, 2.1 mo, p=0.23) and (14 mo, 8.9 mo, 18.5 mo, p=0.14) respectively. Patients responding to first line therapy (CR/PR) had improved OS when compared to those having stable/progressive disease (15.9 mo vs 7.2 mo) (p=0.004) (Figure 1B). Conclusions: Our study results reflect the poor outcomes of ATLL patients, especially in the ones with primary refractory disease to frontline treatments. We also showed the suboptimal activity of frontline regimens for ATLL and lack of unifying therapeutic approach for this lymphoma in the US. Multi-institutional clinical trials exploring novel therapeutic frontline options to improve response rates, which translate in better OS are desperately needed in this population. Disclosures Sandoval-Sus: Massive Bio: Consultancy; Janssen: Consultancy; MorphoSys US: Consultancy; Celgene: Speakers Bureau. Sokol:Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kyowa/Kirin Inc.: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Honoraria, Speakers Bureau.

Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma

Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma