Abstract 5933
Background
Sequencing studies have demonstrated extensive genetic heterogeneity between and within tumor lesions in treated metastatic solid tumor patients. The response of individual tumor lesions to therapy is a reflection of subclonal inhibition and growth in the face of selective pressure. Are there lesion-level progression patterns that would provide insights into the biological heterogeneity that underpins response and resistance?.
Methods
Retrospective review of patients with histologically confirmed metastatic solid tumors who were treated at Massachusetts General Hospital Cancer Center’s phase 1 center from October 1, 2010 to September 30, 2015 and had at least two radiographic assessments, 30 days apart. 769 study participants were enrolled in a phase 1 trial during the study period, of which 575 had at least two radiographic evaluations. 427 participants had more than one lesion at baseline and displayed progression of at least one lesion (growth of at least 20% or a new lesion). We categorized the lesion-level progression patterns of these 427 patients.
Results
Study participants had a mean of 2.6 prior lines of therapy in the metastatic setting with an average of 6.3 tumor lesions on their baseline scan involving an average of 3 organs. Of the 427 study patients with progressive lesions, 24% of patients had progression at a single lesion and 49% of patients had progression in a single organ when they were taken off-study or at data cut-off. 10% of patients exhibited simultaneous response (shrinkage of at least 30%) and progression in different lesions. Across our entire 575 patient cohort, liver lesions were 2.9 times as likely to progress than other lesions regardless of cancer types.
Conclusions
The significant proportion of patients with progression at a single lesion or organ demonstrates that clonal heterogeneity has important clinical implications. Liver lesions may have microenvironment-specific factors that increase the likelihood of progression relative to other organ sites.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Chen: Advisory / Consultancy: Blackstone Life Sciences; Advisory / Consultancy: HotSpot Therapeutics; Advisory / Consultancy: Foundation Medicine. D. Juric: Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Eisai; Advisory / Consultancy: Syros; Advisory / Consultancy: Ipsen; Research grant / Funding (self): Eisai; Research grant / Funding (self): Genentech; Research grant / Funding (self): Celgene; Research grant / Funding (self): Takeda; Research grant / Funding (self): javascript:%20create_table_line(’1’,%20new%20Array(’ent’,%20’des’,%20’tor’));Celgene; Research grant / Funding (self): Placon Therapeutics; Research grant / Funding (self): Syros; Research grant / Funding (self): EMD Serono; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
3158 - Tobacco Retail Access and Tobacco Cessation Among Head and Neck Cancer (HNC) Survivors
Presenter: Lawson Eng
Session: Poster Display session 1
Resources:
Abstract
5511 - ASSERT: A Prospective, Observational Study Measuring Sodium Improvement and Outcomes in Patients Treated for Moderate to Severe Hyponatremia Secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in Italy (Lung Cancer Cohort)
Presenter: Rossana Berardi
Session: Poster Display session 1
Resources:
Abstract
3821 - Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: A systematic review and meta-analysis.
Presenter: Benedetta Bonardi
Session: Poster Display session 1
Resources:
Abstract
2168 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy
Presenter: Tineke Vandenbroucke
Session: Poster Display session 1
Resources:
Abstract
5855 - Update of the registry of young women with cancer by the International Network of Cancer, Infertility and Pregnancy
Presenter: Charlotte Maggen
Session: Poster Display session 1
Resources:
Abstract
5156 - Erectile dysfunction in patients with metastatic renal cell carcinoma
Presenter: Ilya Tsimafeyeu
Session: Poster Display session 1
Resources:
Abstract
4992 - Exercise level, interest and preferences in cancer patients.
Presenter: Alice Avancini
Session: Poster Display session 1
Resources:
Abstract
3427 - Filling the Gaps in Informed Consent for Advanced Cancer Patients considering Phase 1 Oncology Trials - an in-depth Qualitative Study of Key Stakeholders at a large United Kingdom Phase 1 unit
Presenter: Abhijit Pal
Session: Poster Display session 1
Resources:
Abstract
3537 - Breast Cancer Patients’ Quality of Life: Real World Data
Presenter: Thanos Kosmidis
Session: Poster Display session 1
Resources:
Abstract
4761 - High-sensitivity troponin as a cardiotoxicity biomarker in breast cancer treatment
Presenter: Joana Simões
Session: Poster Display session 1
Resources:
Abstract