11607 Background: Validated biomarkers of response to immune checkpoint inhibitors are needed. Methods: INSPIRE (NCT02644369) is a biomarker-driven study to comprehensively evaluate changes in genomic and immune landscapes in tumors and blood of patients (pts) treated with pembro at 200 mg IV Q3W. It consists of 5 histological cohorts of 20 evaluable pts each: head and neck squamous cell cancer (SCCHN), triple negative breast cancer (TNBC), high grade serous ovarian cancer (HGSOC), melanoma (MM) and mixed solid tumors (MST). All pts undergo pre- and on-treatment (week 6-9) fresh tumor biopsies (bx), and at progression for responders. The first core bx is for immunohistochemistry and subsequent cores are pooled to create single cell suspension for 5 prioritized biomarker assay groups: (1) whole exome/RNA-/TCR-sequencing; (2) T/B/NK, APCs, and/or Treg phenotyping; (3) patient-derived xenografts; (4) RNA-seq on viably sorted immune populations; (5) TIL expansion and characterization. Serial blood samples for immunophenotyping, chemokines/cytokines and ctDNA are collected. Results: 53 pts were enrolled from March 21, 2016-January 16, 2017 (5 SCCHN, 8 TNBC, 17 HGSOC, 7 MM, 16 MST). 84 tumor bx (53 pre-, 30 on-treatment, 1 progression) and 244 blood-based biomarker samples have been collected. The most common sites of tumor bx were: lymph nodes (27%), liver (22%) and skin (14%) (see table). For the 5 cohorts, the % of tumor bx with sufficient cellularity for biomarker assay groups 1 and 2 are: SCCHN (33%), TNBC (9%), HGSOC (52%), MM (55%), MST (55%). Conclusions: This report provides robust technical feasibility data to plan immune and molecular characterization of tumor and blood-based biomarkers in pts receiving ICI. Clinical trial information: NCT02644369. [Table: see text]
9563 Background: With the evolving treatment landscape in metastatic melanoma, approaches to disease surveillance post resection in stage 3 disease requires reconsideration. We previously reported the outcomes of sub-stage-specific schedules of combined fluorodeoxyglucose-positron emission and computerized tomography (PET/CT) surveillance at high risk of relapse following surgery. The aim of this study was to provide an update on our surveillance protocol with an extended sample size and longer duration of follow-up. Methods: From 2009, patients with AJCC stage 3 melanoma underwent PET/CT scans according to pre-specified schedules based on Bayesian probabilities of sub-stage-specific relapse. Schedules were stage 3A: 6, 18 mo; stage 3B: 6, 12, 18, 24, 36, 48, 60 months; stage 3C: 6, 12, 18, 24, 36 months. Contingency tables were used to evaluate the sensitivity, specificity and predictive values of these schedules. Results: In total, 171 patients (3A: 34; 3B: 93; 3C:44) underwent 553 PET/CT scans with a median follow up of 47 months. Relapses were identified in 65 (38%) patients of which (72%) were asymptomatic at the time of radiologically documented relapse. False positive results occurred in 8%. The positive predictive value (PPV) of an individual scan for diagnosing true recurrence was 77% (64-87%). Negative scans at 6 months had negative predictive values (NPV) between 57% in Stage 3A to 69% in Stage 3B for relapse. Sensitivity and specificity of the overall approach of sub-stage-specific PET/CT surveillance for detecting disease relapse were 70% and 89%, respectively. Evaluable predictive values for detecting disease relapse were: stage 3A: PPV:56%, NPV:76%; 3B: PPV 83%, NPV 86%; stage 3C: PPV 84%, NPV 84%. 32 of 65 patients (49%; 3A: 1; 3B: 7; 3C: 2) underwent resection of relapsed disease and 10 of these patients remained free of disease with a median follow-up of 24 months. Conclusions: Sub-stage-specific PET/CT is effective in detecting asymptomatic recurrence in stage 3 melanoma, and is associated with a high rate of disease resection at relapse.
Abstract Although genomic data sharing is widely endorsed, practical barriers exist. For example, annotation and calling of mutations vary significantly with the method used. This poses clear challenges in data harmonization and sharing. In this setting, GA4GH conducted a survey of Cancer Next Generation Sequencing (NGS) initiatives globally to chart the technical implementation of genomic programs. A total of 59 of 108 invited initiatives responded (response rate = 55%) via a web-based survey. In total, 63% of programs share their data, and 10% are partially sharing or planning to share. Most initiatives were North American (33%) or European (28%) based. Of the 59 respondents, 51 responded to queries on technical aspects of their NGS program (Table 1). For diagnostic application, 67% employ a small panel (<50 genes), 55% a medium panel (50-250 genes), 45% a large panel (251-1000 genes); only 22% indicated they (also) use whole exome sequencing (WES). Diagnostic programs tend to favor panels and deep sequencing, while research programs favor WES/WGS. Overall, mutation and copy number calls were stored centrally in a single project database (96% and 92% respectively), with lower rates for raw data (BAM files, 86%) and histological data (75%). Somatic mutations were identified primarily via GATK (57%), Samtools (49%), Varscan (47%), MuTect (40%); all but 7 initiatives used combinations of these tools. Mutational variants were annotated by Cosmic (73%), PolyPhen (66%), and dbSnp (64%). Germline samples were used as control in only 62% of initiatives. In conclusion, the majority of initiatives use an ensemble of tools for calling and annotating mutational variants. Harmonization efforts on gene panel composition and the standardization of tools (eg, methods, application program interfaces (APIs)) are urgently needed to prevent continued generation of isolated data silos that hamper NGS-enabled advances in precision medicine. Primary purpose of test% Diagnostic (n = 9)% Research (n = 22)% Diagnostic & Research (n = 20)OrganizationCentralized testing22%64%30%Unique sample identifiers89%77%70%Certification ISO/CLIA/NE88%45%65%Initiative > 1000 Patients33%36%35%SequencingSequencing depth 50-250x0%55%80%Sequencing depth >250x100%45%20%Panel sequencing89%68%60%Whole Exome/Genome Sequencing22%77%65%SamplesFresh frozen (FF)11%23%15%Formalin Fixed Paraffin Embedded (FFPE)44%27%20%FFPE or FF44%50%65%Germline as control22%68%65% Citation Format: Daniel J. Vis, Jeremy Lewin, Lillian Siu, Rachel Liao, Jean Claude Zenklusen, Fabien Calvo, Edit Szepessy, Ana Vivancos, Valtteri Wirta, Subha Madhavan, Keunchil Park, Daniel Tan, Janessa Laskin, Melissa Brammer, Emmanuel Dias-Neto, Anthony Tolcher, Thomas J. Hudson, Charles Sawyers, Mark Lawler, Emile E. Voest. Heterogeneity of mutation calling and annotation: a survey of cancer next-generation sequencing initiatives by the Global Alliance for Genomics and Health (GA4GH). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5287.
Testicular germ cell tumour is the commonest malignancy affecting males aged between 15 and 35, with an increased relative risk amongst those with a history of cryptorchidism. In patients presenting with locoregional metastatic disease, retroperitoneal and pelvic soft tissue masses are common findings on ultrasound and computed tomography, which has several differential diagnoses within this demographic cohort. On staging 18F-FDG-PET/CT, understanding the typical testicular lymphatic drainage pathway facilitates prompt recognition of the pathognomonic constellation of unilateral absence of testicular scrotal activity, and FDG-avid nodal masses along the drainage pathway. We describe the cases of three young males presenting with abdominopelvic masses, in whom FDG-PET/CT was helpful in formulating a unifying diagnosis of metastatic seminoma, retrospectively corroborated by a history of testicular maldescent.In all three cases, the patients were males aged in their 30s and 40s who were brought to medical attention for back and lower abdominal pain of varying duration. Initial imaging evaluation with computed tomography and/or ultrasound revealed large abdominopelvic soft tissue masses, with lymphoproliferative disorders or soft tissue sarcomas being high on the list of differential diagnoses. As such, they were referred for staging FDG-PET/CT, all of whom demonstrated the pathognomonic constellation of, 1) unilateral absence of scrotal testicular activity, and 2) FDG-avid nodal masses along the typical testicular lymphatic drainage pathway. These characteristic patterns were corroborated by a targeted clinical history and examination which revealed a history of cryptorchidism, and elevated β-hCG in two of three patients. All were subsequently confirmed as metastatic seminoma on biopsy and open resection.These cases highlight the importance of clinical history and examination for the clinician, as well as a sound knowledge of the typical testicular lymphatic drainage pathway for the PET physician, which would assist with prompt recognition of the characteristic imaging patterns on FDG-PET/CT. It further anecdotally supports the utility of FDG-PET/CT in evaluating undiagnosed abdominopelvic masses, as well as a potential role in the initial staging of germ cell tumours in appropriately selected patients.
PURPOSE: Participation in cancer clinical trials (CCTs) for adolescents and young adults (AYAs) remains the lowest of any patient group with cancer. Little is known about the personal barriers to AYA accrual. The aim of this study was to explore AYA attitudes that influence CCT participation. METHODS: A mixed-methods approach was used. AYAs and non-AYAs (≥ 40 years) completed the Cancer Treatment subscale of the Attitudes Toward Cancer Trials Scales and 9 supplementary questions formed from interview analysis. Differences between AYA and non-AYA cohorts were analyzed using the Mann-Whitney U test, and logistic regression models were constructed to evaluate the effect of demographics on perceptions of CCTs. RESULTS: Surveys were distributed to 61 AYAs (median age, 29 years; range, 17-39 years) and 74 non-AYAs (median age, 55 years; range, 40-88 years). Compared with non-AYAs, AYAs perceived CCTs to be unsafe/more difficult (Personal Barrier/Safety domain; P = .01). There were no differences based on age in other domains. AYAs were also more concerned with CCT interference in their long-term goals ( P = .04). Multivariable ordered logistic regression identified increased personal barriers in the Personal Barrier/Safety domain for AYAs ( P = .01), in patients with English as a second language (ESL; P < .01), and in patients previously not offered a clinical trial ( P = .03). Long-term goals were identified as a barrier in particular tumor types ( P = .01) and in patients with ESL ( P < .01), with a trend identified in AYAs ( P = .12). CONCLUSION: Age-related differences in attitudes toward CCTs suggest that tailored approaches to CCT accrual are warranted. Patient-centered delivery of information regarding CCTs, particularly in patients with ESL and who are trial naïve, may improve accrual.
A curiosity has therefore arisen over time relating to the availability of, and access to, clinical supervision within Australian Youth Cancer Services and how healthcare professionals perceive the role of supervision in supporting the delivery of quality youth cancer care. This chapter reports on the qualitative component of a larger mixed-methods study that aimed to address this question. Youth Friendly Care has evolved from recognition of the unique impacts experienced by young people facing ill health and the challenges faced by professionals in caring for them. Clinical supervision, also referred to as 'supervision', is considered a vital part of modern, effective healthcare practice and is embedded in many healthcare systems and professions. The chapter explores the availability of, and access to, clinical supervision for healthcare professionals working in Australian Youth Cancer Services and their perceptions of the role of supervision in supporting the delivery of quality youth cancer care.
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