Recommendations were put together by the WHO in the 1980s to standardize the response assessment of anticancer therapy (Miller et al. 1981). In the 1980s, members of the WHO met to put forth recommendations that investigators would use to report patient data and outcomes following a standardized pattern. This methodology helped various researchers to compare their results. These recommendations introduced the concept of utilizing tumor response criteria as an endpoint for many clinical trials. Assessment of tumor burden was determined by bidimensional lesion measurements. The WHO recommendations utilized any change from baseline evaluation as response to therapeutic interventions (Miller et al. 1981). A high rate of interobserver variability and imprecise definitions for practical implementation led to the development of the RECIST criteria.

Important endpoints of early phase clinical trials are evaluated by tumor shrinkage and time to development of disease progression (Eisenhauer et al. 2009). Some issues with the WHO criteria included methods of incorporating change in size of measurable disease, minimum number of lesions to be recorded, and definition of progressive disease (Therasse et al. 2000). The lack of clearly stated criteria led to modifications by the cooperative groups and pharmaceutical companies. Valid comparisons were unable to be performed to adequately interpret the results of clinical trials (Tonkin et al. 1985). Due to these circumstances and introduction of newer radiographic technologies, the International Working Group was created in the 1990s to help clarify and revisit standard definitions of response criteria. These criteria were called RECIST, Response Evaluation Criteria in Solid Tumors, and were published in 2000. These guidelines were widely accepted by the EORTC, US NCI, NCI Canada Clinical Trials Group, and other cooperative groups and play a large role in current early phase clinical trials to determine overall evaluation of tumor burden and response to therapy. Several of the recommendations put forth in this version were based on retrospective clinical data. Because of this, large-scale validation studies were performed to monitor the implementation of these guidelines in prospective studies (Therasse et al. 2006). The International Cancer Imaging Society (ICIS) and radiology groups reported concerns regarding lesion measurements, especially in patients with bone or nodal metastases, methods of measuring maximum diameter, and the need for standardizing reporting techniques in relation to measurements, contrast enhancement of lesions, and adequate comparisons to prior imaging studies (Bellomi and Preda 2004; Husband et al. 2004).

RECIST criteria are now used to define response rate and time to progression irrespective of the stage of development of new cancer therapeutics. Overall tumor burden is defined at baseline and then used as comparison for subsequent measurements. Measurable disease is defined by the presence of one measurable lesion. This is measured in at least one dimension in the longest diameter, with a minimum of 10 mm by CT scan or 20 mm by chest X-ray. Lymph nodes must be ≥15 mm in short axis by CT scan. Other lesions <10 mm or pathological lymph nodes ≥10 mm and <15 mm are considered non-measurable. Other non-measurable lesions include leptomeningeal disease, ascites, pleural or pericardial effusion, abdominal masses, or abdominal organomegaly that is identified by physical exam that is not seen on reproducible imaging techniques (Eisenhauer et al. 2009).

Complete response (CR) is defined as disappearance of all target lesions and reduction of any pathological lymph nodes to <10 mm. Partial response (PR) is defined as at least 30 % decrease in the sum of the diameters of the target lesions from baseline measurements. Progressive disease (PD) is defined as at least 20 % increase in the sum of the diameters of the target lesions. In addition to this increase, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Stable disease (SD) is defined as neither sufficient shrinkage that qualifies for PR nor sufficient increase that qualifies for PD with reference to the smallest sum diameter of the baseline lesions. Best overall response is the best response recorded from the start of the study treatment until the end of the treatment.

Despite all these recommendations, there are multiple biases when reporting size criteria. More recently, RECIST has been modified to take functional biological information into consideration (Ganten et al. 2014). The PERCIST (PET Response Criteria in Solid Tumors) was proposed in 2009 and takes into account biological information from PET imaging, especially in those patients treated with newer therapies, during response evaluation. Most new cancer therapies are more cytostatic than cytocidal. Tumor response may be associated with a decrease in metabolism rather than a major decrease in tumor size (Tirkes et al. 2013). This concept has been put forth in practice for response categories for patients with lymphomas (Wahl et al. 2009; Cheson et al. 2007). Response is evaluated as a percentage change in SUV_max or SUL (lean body mass-normalized SUV) for the most active lesion at each time of evaluation. Adherence to standardized PET/CT scanning protocol that includes consistency in injected dose, postinjection delay, and SUV normalization technique is crucial (Tirkes et al. 2013). These criteria continue to be modified to adapt to advancing technology and drug development.

Follow-up of bone tumors is to detect local recurrences or development of metastatic disease when early treatment is still possible and may show effectiveness. Imaging of the primary lesion and lung imaging with chest X-ray or CT chest are the recommended norm. There are no randomized data that describe the frequency and extent of follow-up in patients with bone sarcomas. Overall, the majority of those with osteosarcoma recur with lung metastasis, and those with the Ewing family of tumors have a higher incidence of skeletal metastasis (Ferrari et al. 2013). Various guidelines have been put together by the COG and the European Working Groups. Recommended intervals by the ESMO/EuroBoNet working group suggests every 6 weeks to 3 months for the first 2 years after completion of chemotherapy, every 2–4 months during years 3–4, every 6 months for years 5–10, and then approximately every year (Hogendoorn et al. 2010). Similar recommendations have been put forth by the COG and are described below for osteosarcoma and Ewing sarcoma (Tables 13.2 and 13.3).