Background: Despite their potential to improve patient quality of life and survival, PRO-based symptom assessments are not routinely used in clinical cancer care. Barriers to use include cost, availability to for-profit users, and data sharing mandates as well as restrictions to any modification or translation to mobile devices. A trustworthy, open, and flexible approach to PRO-based symptom assessment may create new opportunities to reduce patient burden, increase clinical insight, and maximize measurement quality. Methods: We conducted expert interviews with oncology care staff, patients, and psychometricians to develop a flexible framework for symptom assessment that could be used to provide clinical insight and, uniquely, provide unidimensional measurements supported by item response theory. We developed a scalable framework to create symptom assessments using four interchangeable components, recall period, construct (e.g., severity, frequency, control), symptom (e.g., nausea, fatigue, pain), and an optional qualifier (e.g., at its worst, on average, in your lower back) In its first iteration, we tested 18 questions measuring presence as well as the severity, frequency, and impairment related to 9 symptoms occurring over the previous 7 days. We assessed construct validity by comparing scores to the PRO-CTCAE and assessed scalability and dimensionality using Mokken analysis. We recruited cancer patients receiving therapy in the United States to complete the nascent assessment alongside the PRO-CTCAE. Results: We recruited 10 patients and 13 clinical and psychometric domain experts for the expert interviews to develop the framework. For validation, we recruited 251 patients. Fatigue (65%) was the most common symptom and vomiting (32%) the least. All items correlated with the PRO-CTCAE equivalents (r = 0.46 - 0.72, all P < 0.05). Mokken analysis confirmed the scalability and dimensionality of all symptom scales with multiple items (Ho = 0.59 - 0.72) as well as their constituent items (Ho = 0.49 - 0.66). Conclusions: We created a flexible framework using exemplar PRO-based symptom assessments that can flexibly provide clinical insights and robust research measurements depending on stakeholder need. In the future, we plan to share access and encourage its use and expansion. Further work is planned to increase the number of symptoms and number of questions per symptom available within the framework.