Examination of The Characteristics of Long-Term Survivors Among Patients With Gallbladder Cancer With Liver Metastasis Who Underwent Surgical Treatment: A Retrospective Multicenter Study (ACRoS1406)

Background: Gallbladder cancer (GBC) with liver metastasis is considered unresectable. However, there have been infrequent reports of long-term survival in patients with GBC and liver metastases. Therefore, we examined the characteristics of long-term survivors of gallbladder cancer with liver metastasis.Methods: A retrospective multicenter study of 503 patients with GBC (mean age, 68.6 years; female, 52%) was performed. Although patients with pre-operatively diagnosed GBC and liver metastasis were generally excluded from resection, some cases identified during surgery were resected.Result: In patients with resected stage III/IV GBC (n = 228), the period 2007–2013 (vs. 2000–2006, hazard ratio 0.55), other type histology (vs. well/moderate histology, hazard ratio 2.34), ≥2 liver metastases (vs. one liver metastasis, hazard ratio 4.30), and positive margin resection (vs. complete resection with a negative margin, hazard ratio 1.57) were independent prognostic factors for overall survival, whereas one liver metastasis (vs. no liver metastasis) was not. The 5-year overall survival and median survival times in those with one liver metastasis with complete resection and a negative margin (40.9%, 28.3 months) were significantly better than those in patients with ≥2 liver metastases with complete resection and a negative margin (0%, 11.0 months, p = 0.025), and comparable to those in patients with liver metastasis with complete resection and a negative margin (37.0%, 33.0 months). According to the univariate analysis of resected patients with GBC and liver metastases (n=24), minor hepatectomy, less blood loss, less surgery time, papillary adenocarcinoma, T2, morbidity of Clavien–Dindo classification ≤ 2, and adjuvant chemotherapy were significantly associated with longer survival. Long-term survivors (n = 5) had a high frequency of T2 tumors (4/5), had small liver metastases near the gallbladder during or after surgery, underwent minor hepatectomy without post-operative complications, and received post-operative adjuvant chemotherapy.Conclusions: Although there is no surgical indication for GBC with liver metastasis diagnosed pre-operatively, minor hepatectomy and post-operative chemotherapy may be an option for selected patients with T2 GBC and liver metastasis identified during or after surgery who do not have other poor prognostic factors.

Considerations for Optimal Administration of Chimeric Antigen Receptor (CAR) T-Cell Therapy Programs: A Multi-Stakeholder Qualitative Analysis

CAR-T therapies represent a novel advance in oncology, albeit at list prices that exceed $373,000 (and that does not capture their total cost to the healthcare system). Since initial product approval in 2017, stakeholders and observers have attempted to investigate clinical and financial impacts of CAR-T therapies, and potential approaches to optimizing access and use by eligible patients. Most existing research is from a single stakeholder perspective - patients, providers, or payers - limiting the ability to draw broader conclusions on trends and offer prospective recommendations. To address this knowledge gap, we sought to identify and describe critical success factors for optimal delivery of CAR-T therapies. We undertook a qualitative study based on interviews with multiple US-based stakeholders including clinicians, financial and operations staff, and payer-insurers. Interviewees--which included oncologists (n=6), facility financial and operational personnel (n=4), and coverage and reimbursement decision-makers from US health plans (n=3)--completed structured, live, hour-long, interviews covering clinical, administrative, and general topics on patient access to CAR-T therapies. All clinicians had experience with ≥1 FDA-approved CAR-T therapies in both registered clinical trials and clinical practice; financial and operational personnel were affiliated with the same facilities as the clinicians, and also had real-world experience with these therapies; payer representatives were directors from a large national commercial plan, regional integrated delivery network, and a Medicare administrative contractor, respectively. Consensus facility feedback (i.e., clinicians, operational personnel) was that CAR-T is effective, and that their administrative processes had been optimized through care team coordination and experience-based efficiencies; in contrast, 2 of 3 payer interviewees expressed that, while CAR-T therapies have shown efficacy, their real-world benefits and applicability are less well-defined. Facility interviewees noted that: (1) reimbursement from commercial insurers is higher than from Medicare, with the latter associated with per-patient net-neutral or negative margins; (2) when possible, differential reimbursement between inpatient and outpatient settings may drive patient management towards outpatient care; and (3) negative-margin cases are currently deemed acceptable due to nonclinical factors (i.e., competitive pressure within a geographic region, anticipated branding/marketing value) and relatively small treated populations. From payer interviewees, CAR-T cost and perceived cost-to-value have made health plans more receptive to considering outcomes-based contracting, capitated provider payments, or other mitigation methods. Left unoptimized, these factors may adversely impact patient access to, and long-term provider attractiveness of, CAR-T therapies. All interviewees agreed that as the CAR-T marketplace grows, a strong preference exists for manufacturers to develop and communicate for their therapies durable outcomes data, clear and comprehensive reimbursement information, and competitive pricing. With the potential for many approved products in a single indication, and/or a single approval for indications with relatively large eligible patient populations, interviewees also conveyed interest in compelling health economic data. Facility interviewees also acknowledged that if it remains an overall net-negative margin service, new providers will be less able to start CAR-T programs and smaller programs may encounter sustainability issues, collectively jeopardizing patient access to these life-changing therapies. Overall, findings from this study suggest that during the continued maturation of the landscape, stakeholders will need to be proactive to ensure that CAR T-cell therapies can be maintained amidst financial and operational pressures. Several CAR-T therapy options for multiple myeloma are on the immediate horizon, likely increasing demand among eligible patients. Accordingly, the need to link real-world evidence of the clinical value and institutional investment burden of these therapies to reimbursement is imperative, both to insulate payers and enable clinicians to provide innovative therapies. Figure 1 Figure 1. Disclosures Faber: Amgen: Honoraria; Adaptive: Honoraria; Cardinal Health: Honoraria; Celgene: Honoraria; Astra Zeneca: Honoraria; GlaxoSmith Kline: Honoraria; Janssen: Honoraria; Juno: Honoraria; Karyopharm: Honoraria; Kite: Honoraria; Takeda: Honoraria; Sanofi Genzyme: Honoraria. Hunter: BMS: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Deol: Kite, a Gilead Company: Consultancy. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Riccobono: Legend Biotech: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Garrett: Legend Biotech USA: Current Employment. Jackson: Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Fowler: Amgen: Ended employment in the past 24 months; Janssen: Current Employment. Berger: Janssen Scientific Affairs: Consultancy, Research Funding. Lorden: Janssen Scientific Affairs: Consultancy, Research Funding. Stewart: Janssen Scientific Affairs: Consultancy, Research Funding.

Outcomes of Surgery for Sacral Chordoma and Impact of Complications: A Report of 50 Consecutive Patients With Long-Term Follow-Up

Study Design: Retrospective case series. Objective: To determine predictive factors of overall survival (OS) and local recurrence (LR), report complications, and assess the impact of complications on survival, recurrence, and function in patients undergoing en bloc resection of sacral chordoma. Methods: This retrospective case series was obtained from a prospective database (1995-2016). All patients underwent en bloc resection of sacral chordoma. Demographic, perioperative, and complication data were collected. Outcomes included: overall survival(OS), local recurrence(LR), and complications. Survival analysis with multivariable cox regression was performed. Results: Among 50 patients, median follow-up was 5.3 years (range = 1.3-17.2). The majority (82%) underwent a negative margin resection. Survival: 17 patients died (34%) with a median OS of 10.0 years (range = 1.3-17.2). Multivariable cox regression revealed that a negative margin resection was not significantly associated with improved survival (HR = 3.35, 95%CI 0.87-12.80, P = .078). Recurrence: 20 patients (40%) experienced LR with a median time of 6.2 years (range = 0-16.9). Multivariable cox regression revealed that a negative margin resection was associated with a significant decreased risk of LR (HR = 4.96, 95%CI 1.84-13.34, P = 0.002,). A 62% overall complication rate was seen (42% major), with 26% reoperation rate. Of the reoperations, 54% were delayed (>6 weeks after the index surgery). Multivariable cox regression demonstrated that neither major complication nor reoperation significantly impacted OS (HR = 0.62, 95%CI 0.22-1.79, P = 0.380), LR (HR = 1.28, 95%CI 0.49-3.36, P = 0.611), or functional outcomes (OR = 2.94, 95%CI 0.25-34.8, P = 0.393). Conclusions: Negative margin resection was associated with decreased LR. Neither major complication nor reoperation significantly impacted OS, LR, or functional outcome. Though additional studies are needed, it appears that despite the morbidity associated with sacral chordoma resection, the long-term clinical outcomes are favorable.

Optimal margins for early stage peripheral lung adenocarcinoma resection

Background A pathologically confirmed negative margin is required when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma. However, the optimal margin distance to ensure complete tumor resection while preserving healthy lung tissue remains unknown. We aimed to establish a reliable distance range for negative margins. Methods A total of 52 intraoperative para-cancer tissue specimens from patients with peripheral lung adenocarcinoma with pathological tumors ≤2 cm in size were examined. Depending on the distance from the tumor edge (D), the para-cancer tissues were divided into the following five groups: D < 0.5 cm (group I); 0.5 cm ≤ D < 1.0 cm (group II); 1.0 cm ≤ D < 1.5 cm (group III); 1.5 cm ≤ D < 2.0 cm (group IV); and D ≥ 2.0 cm (group V). During pathological examination of the specimens under a microscope, the presence of atypical adenomatous hyperplasia or more severe lesions was considered unsafe, whereas the presence of normal lung tissue or benign hyperplasia was considered safe. Results Group V, in which the margin was the farthest from the tumor edge, was the safest. There were significant safety differences in between groups I and V (χ2 = 26.217, P < 0.001). Significant safety differences also existed between groups II and V (χ2 = 9.420, P < 0.005). There were no significant safety differences between group III or IV and group V (P = 0.207; P = 0.610). Conclusions We suggest that when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma with pathological tumor sizes ≤2 cm, the resection margin distance should be ≥1 cm to ensure a negative margin.

Toluidine blue for extramammary Paget’s disease in Mohs micrographic surgery

Introduction: We report an elderly gentleman with Extramammary Paget’s disease (EMPD) treated with Mohs micrographic surgery (MMS) using Toluidine blue staining intraoperatively as to detect the Paget’s cells. Case Presentation: An elderly man presented with an erythematous plaque on the left inguinal fold which showed in-situ EMPD on histopathological examination. Investigations for secondary EMPD were negative and the patient was treated with MMS. During MMS, the specimens from the patient were stained using Toluidine blue in order to detect the Paget cells and to determine the appropriate negative margin. At 4 years follow up the patient is free of recurrence. Conclusion: Toluidine blue is a fast, user-friendly dye that can be used intraoperatively during MMS as to detect Paget cells and thus to determine the appropriate negative margin.

An Unexpected Finding of Gastrointestinal Stromal Tumors During Laparoscopic Sleeve Gastrectomy; How to Deal? How Much Safety Margin Needed?

Background: There is an increasing incidence of coincidental gastric gastrointestinal stromal tumors (GIST) during a laparoscopic sleeve gastrectomy (LSG). Resection with negative margin R0 is the safest and most proper treatment. Objectives: The incidence of GIST in patients undergoing LSG and resection with a 1- to 2-cm safety margin was validated and analyzed. The primary endpoint is that can simultaneous excision be oncologically adequate or not? How much GIST is supposed to be far from a staple line? Methods: The present prospective study included 338 patients with body mass index (BMI) ≥ 35. All patients underwent LSG without known history or imaging reveal GIST. Resection was done with a safety margin of 1 to 2 cm away from the stapled margin and, then, sent for histopathology and immunohistochemically staining. Results: A total of 17 patients (5%) had coincidental GIST. The size was T1 in 88.2% of patients; 16 patients were staged as IA according to the American Joint Committee on Cancer (AJCC TNM). Safety margin was ≤ 1 cm for 3 patients to avoid incorporation in staple line and 14 patients (82.3%) had 2 cm safety margin. Resection margin in biopsy revealed positive resection margin R1 for 2 patients, whose safety margin was only 1 cm or less. A total of 15 patients had a negative margin (R0), whose safety margin was 2 cm. Conclusions: Any incidental GIST can be removed safely during LSG as long as it is far from the staple line with at least a 2-cm safety margin and negative resection margins without changing the procedure. Margins less than 1 cm are associated with adverse prognostic factors.