Determining lines of therapy in patients with solid cancers: a proposed new systematic and comprehensive framework

Abstract

The complexity of neoplasia and its treatment are a challenge to the formulation of general criteria that are applicable across solid cancers. Determining the number of prior lines of therapy (LoT) is critically important for optimising future treatment, conducting medication audits, and assessing eligibility for clinical trial enrolment. Currently, however, no accepted set of criteria or definitions exists to enumerate LoT. In this article, we seek to open a dialogue to address this challenge by proposing a systematic and comprehensive framework to determine LoT uniformly across solid malignancies. First, key terms, including LoT and ‘clinical progression of disease’ are defined. Next, we clarify which therapies should be assigned a LoT, and why. Finally, we propose reporting LoT in a novel and standardised format as LoT N (CLoT + PLoT), where CLoT is the number of systemic anti-cancer therapies (SACT) administered with curative intent and/or in the early setting, PLoT is the number of SACT given with palliative intent and/or in the advanced setting, and N is the sum of CLoT and PLoT. As a next step, the cancer research community should develop and adopt standardised guidelines for enumerating LoT in a uniform manner.

Development of a Machine Learning Model Using Limited Features to Predict 6-Month Mortality at Treatment Decision Points for Patients With Advanced Solid Tumors

“…Any anticancer therapy (chemotherapy, biologics, targeted therapy, immunotherapy, and hormonal therapy) entered into EHR treatment plans was defined as an eligible LoT, consistent with a recently published framework. 30 Injectable and selected oral hormonal therapies for prostate and breast cancer were not included. Finally, to define a TDP, we identified a visit within 30 days before the LoT start date with values for required features.…”

Cross-Resistance Among Sequential Cancer Therapeutics: An Emerging Issue

“…For this reason, many patients affected by advanced malignancy receive sequential anti-cancer therapies, which may include chemotherapy, immunotherapy, targeted therapy, endocrine therapy, or a combination of them. The complexity requires strict criteria to define and enumerate the sequential lines of therapy uniformly across solid malignancies (12). From a mechanistic point of view, recent high-throughput sequencing studies and quantitative modeling approaches have revealed extensive intratumor heterogeneity and highly dynamic tumor clonal evolution under the selective pressure exerted by drug treatments (13)(14)(15).…”

Ruthenium-based antitumor drugs and delivery systems from monotherapy to combination therapy

“…From NAMI-A to KP1019, KP1339, and TLD1433, the development of ruthenium antitumor drugs is moving from monotherapy to combination therapy. 31 Combination therapy for cancer includes combination of multiply drugs and the combination of multiple modalities [32][33][34] , including chemotherapy, radiotherapy, photodynamic therapy, photothermal therapy, immunotherapy and gene therapy, etc. 3,[35][36][37] .…”