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18F-FDG PET/CT is recommended in the staging and treatment planning of lung cancer. There is no consensus on the optimal imaging technique for assessing response to treatment in lung cancer. However, FDG PET/CT is widely used for evaluating response in lung cancer treated with different modalities. Morphological imaging, like CT, cannot accurately differentiate viable residual tumour from postradiotherapy changes. The metabolic response is being evaluated by either the EORTC criteria or the PERCIST criteria. The benefits of using FDG PET/CT in assessing treatment response are manifold. In general, FDG PET/CT can reliably discriminate residual tumour from treatment-related inflammation and fibrosis. 18F-FDG PET/CT, when performed for response assessment, has several advantages over conventional imaging. In this chapter, clinical examples of the strengths and limitations of 18F-FDG PET/CT in the evaluation of treatment response in lung cancers are illustrated.

PET/CT has emerged as ‘standard of care’ modality for imaging of lymphomas, with its utility has been established for staging, restaging, response assessment and surveillance. Fluoro-deoxy-glucose (FDG) targets the glucose transporter receptor and thereby localises in proliferating lymphoid tissue. However, as the modality has evolved over last decade, multiple artefacts, variants and pitfalls were identified. We collated the artefacts, variants and pitfalls documented in literature and by personal experience in this chapter.

Sarcomas are a group of tumors arising from bone, muscle, and other connective tissues. 18F-FDG has been evaluated for use in sarcoma imaging, including treatment response evaluation. In general, patients with intermediate and high-grade tumors are often treated with neoadjuvant chemotherapy and radiotherapy. There are several advantages and limitations of using 18F-FDG PET/CT in assessing treatment response in soft tissue sarcomas. In this chapter, several case scenarios in response assessment of soft tissue sarcomas with 18F-FDG PET/CT are illustrated.

18F-FDG PET CT has changed the way we look at Non-Hodgkin Lymphoma (NHL). FDG PET CT is used for staging and response assessment in NHL. In this chapter we discuss the role of PET CT in assessing NHL.

Pediatric lymphomas represent a number of different conditions which can be quite heterogeneous. Accurate diagnosis, staging, and response assessment are essential. 18F-FDG PET-CT often provides additional anatomical and functional information. Conventional imaging is often used in follow-up based on clinical suspicion. PET/CT is more accurate than radiological imaging and is useful in the management of childhood lymphomas. PET-CT might be helpful in patients with clinical relapse to assess the extent of disease. The article will illustrate the role of 18F-FDG PET-CT for evaluating treatment response in paediatric patients.

The introduction of targeted therapies and, mostly, immune checkpoint inhibitors (ICI) has positively revolutionized the scenario of cancer treatment. In this chapter, we provide an overview of ICI’s current landscape as well as the continued challenge of response assessment with these new agents in our clinical practice.

Cancer generically refers to a group of diseases showing an uncontrolled division of abnormal cells potentially having the ability to invade, through the blood and lymph systems, nearby tissues or spread to other parts of the body.

The management approach in Hodgkin (HL) and high-grade non-Hodgkin lymphomas (NHLs) has shifted toward reducing the toxicity and long-term adverse effects associated with treatment while maintaining favorable outcomes in low-risk patients. The availability of more effective therapies for lymphoma provides a rationale for accurate diagnostic tests and updated patient evaluation, staging, and response criteria. In this regard, positron emission tomography (PET) using fluorodeoxyglucose (FDG) with computed tomography (CT) has proved effective as a metabolic imaging tool with compelling evidence supporting its superiority over conventional modalities, particularly in staging and early evaluation of response, and is now integrated into the routine staging and restaging algorithm of lymphomas. A semiquantitative parameter for measuring tumor glucose metabolism, the maximum standardized uptake value (SUVmax), reflects aggressiveness of neoplasm and is proven to be an important survival predictor. Several quantitative metrics including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) appears to be dependable and reproducible prognostic indicators. Additionally, the 5-point Deauville score (DS) has been recommended as a qualitative method for evaluating interim and end-of-treatment PET/CT results. This chapter summarizes the data on the proven and potential utility of PET/CT imaging for staging, response assessment, and restaging, describing current limitations of this imaging modality.

Accurate and timely response assessment and follow-up by imaging are pivotal for guiding radiotherapeutic management of head and neck cancer. Primarily, post-treatment imaging should aim to detect tumour recurrence as early as possible in order to maximize success of salvage surgery and determine the need for neck dissection. Second, post-treatment imaging has a pivotal role in the differentiation of tumour recurrence from toxicity-induced complication like necrosis or ulcerations and the detection of delayed onset of locoregional, metastatic recurrence and second primary cancers.

Imaging plays an important role in the staging and management of all main gynaecological tumours. Gynaecological tumours treated primarily with radiotherapy such as cervical, vaginal or vulvar cancer typically show considerable tumour shrinkage during treatment. Following the successful completion of initial treatment, there is no strong evidence to support posttreatment imaging surveillance of asymptomatic women. In general, gynaeco-oncological practice, the initial suspicion of disease relapse relies largely on clinical symptoms rather than radiological evidence. However, once clinical relapse is suspected, imaging plays a crucial role in planning salvage therapy. Typical treatment concepts in locally advanced (non-tubo-ovarian) gynaecological cancers consist of external beam radiotherapy (EBRT) and concomitant chemotherapy followed by brachytherapy. Due to the substantial tumour shrinkage during external beam radiotherapy, the GYN GEC-ESTRO group defined an adaptive target volume concept for MRI-based brachytherapy. So far, target concepts for cervical and vaginal cancer were elaborated. The integration of functional imaging into the delineation process could help to reduce interobserver variations and further differentiate subvolumes with increased risk for recurrence. In cervical cancer, MRI performed at 6 months post end of RT, the cervix should be normal or small in size and of low T2 signal intensity, with no evidence of restricted diffusion, to suggest a complete response. [18F]FDG PET/CT has been shown to be a strong predictor of patient outcome, with better survival outcomes in patients with a complete metabolic response. Imaging plays an essential role when recurrence is suspected. The initial steps will involve confirmation of the relapse, defining the extent of disease and determining the available treatment options. If there is no substrate for rising markers on CT or MRI, an [18F]FDG PET/CT should be performed due to its high sensitivity and specificity in early recurrence detection. Isolated vaginal recurrences are a typical pattern of failure in gynaecological malignancies, in particular for endometrial cancer. Treatment strategies follow the similar principles as for primary vaginal cancer.

Response assessment with imaging in gastrointestinal tumours can serve different clinical goals. In tumour types that are primarily surgically treated, imaging can be used to assess response to neoadjuvant treatment, determine resectability and help decide on the best surgical approach. In patients who are primarily undergoing medical (systemic) treatment, imaging can be used to monitor tumour responsiveness in order to optimize or alter the treatment plan in any patient not achieving a satisfactory response, thereby avoiding prolonged ineffective treatment. In this chapter, the use of imaging in these respective settings will be illustrated using rectal cancer and gastro-enteropancreatic neuro-endocrine tumours (GEP-NET) as examples.

Imaging plays a key role in the assessment of response to therapy in lung cancer, particularly in the definition of disease progression/reduction after chemotherapy (ChT) and/or radiotherapy (RT) and in the subsequent management of the patient. Tumour response criteria have been introduced aiming at standardizing results in cancer treatments. However, measurement errors and limits of such parameters, as well as the complex imaging response patterns observed after the use of newer personalized pharmacological treatments for non-small-cell lung cancer (NSCLC), pose a challenge in the application of common standardized criteria for the response evaluation. The tumour response after RT can present with different patterns and timing, highly dependent on the techniques used. One of the major issues is distinguishing radiation-induced lung injury/disease (RILI/RILD) from tumour recurrence. Therefore, response assessment in lung cancer should evolve according to the advances in lung cancer treatment and the introduction of newer diagnostic techniques, including functional and molecular imaging.

Immunotherapy with checkpoint inhibitors has determined a big impact on patient management in the last decade, leading to unpreceded durable responses to treatment. The peculiarities of the CNS and its supposed “isolation” from the immune system have limited for long time the implementation of these immunotherapeutic agents in patients with primary brain tumors or brain metastases. Recent discoveries and the promising preclinical findings in glioblastoma have encouraged the research and implemented the use of checkpoint inhibitors, vaccines, and other immune-modulating drugs in clinical trials. New therapeutic regimens are frequently followed by the requirement of new criteria for response assessment. The iRANO (Immunotherapy RANO) criteria have been introduced consequently, although challenges in differentiating progression from pseudoprogression persist. Metabolic response with PET can provide useful information in this context and help perform a proper response assessment. In the following sessions, some examples of primary and metastatic brain tumors treated with immunotherapy are shown together with corresponding morphological and metabolic imaging findings.

The role of imaging including FDG PET/CT in response assessment, identification, and monitoring of immune-related adverse events (irAEs) is becoming more important given recent accelerated approvals of immunotherapeutic agents for several tumor types that previously had an extremely poor prognosis and lack of therapeutic options. However, the occurrence of irAEs presents challenges for distinction from progressive malignancy. Prompt and accurate imaging diagnosis of irAEs is important given their clinical impact. Due to ever-increasing the number of immunomodulatory agents with different modes of action and their expanding clinical indications, it is vital that clinicians are aware of various and emerging patterns of response and nonmalignant findings that can be associated with their use. It is therefore critical to systematically document the imaging features of irAEs that can be identified during immunotherapy, either as part of routine therapeutic response assessment or to investigate symptoms.

In pediatric practice, 18F-FDG PET/CT is now considered standard of care for the diagnosis, staging, and posttreatment response assessment for an increasing number of pediatric malignancies. The relative rarity of pediatric tumors, availability of PET/CT scanners, and development of pediatric-specific protocols have contributed to the slower standardization of PET/CT practices in the pediatric population as compared to adults. Other pediatric-specific challenges, including radiation concerns, use of IV contrast, and requirements for anesthesia, must also be addressed. This chapter will focus on the use of 18F-FDG PET/CT, protocol options, and normal variations in the pediatric patients, in addition to reviewing the evidence-based literature for specific pediatric cancer types and tumor-like non-cancerous lesions. Recent advances in hybrid PET technology are also presented, with an emphasis on the role these technologies play in driving development of molecular imaging techniques and their application to personalized and targeted approaches to pediatric cancer care.

The Response Evaluation Criteria in Solid Tumors (RECIST) guidance was introduced in 2000 and revised as RECIST 1.1 in 2009. RECIST was put together with the goal of standardising and simplifying tumor response criteria. The important role of imaging in response assessment was recognised, and specific imaging guidelines were included. The significant imaging-related changes in RECIST 1.1 in comparison to RECIST 1.0 included a reduction in the number of lesions to be addressed, from a maximum of 10 to a maximum of 5 and from 5 to 2 lesions per organ; assessment of lymph node size; and clarification of what constituted disease progression. The definitions of response within the RECIST guidance are addressed within this chapter in addition to the limitations of using tumor size alone as a biomarker for tumor response. Other methods of assessing tumor response such as response to immunotherapy (iRECIST) and response on PET-CT (PERCIST) are also included.

Glioblastoma (GBM) is the most common malignant brain tumor and accounts for 70% of all primary brain tumors in adults. Despite aggressive multimodal therapy including surgery, radiation, and chemotherapy, the prognosis remains poor with a median survival of around 2 years. Tumor-treating fields (TTFields) is a new frontier in cancer therapy and has been recently approved for the treatment of GBM. This chapter discusses emerging concepts of brain tumor management, with special emphasis toward novel therapeutic approaches. Recent neuroimaging advances including novel physiologic and metabolic neuroimaging techniques and their role in monitoring treatment-related temporal characteristics and assessing response to this unique treatment modality will also be reviewed.

The previous edition of the consensus guidelines of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), published in 2008, has found broad acceptance by physicians and investigators caring for patients with CLL. It is not the aim of the iwCLL guidelines to provide treatment recommendations, but definitions for the initial assessment, indication for treatment, and response assessment of CLL. Recent advances including the discovery of the genomic landscape of the disease, the development of genetic tests with prognostic relevance, the assessment of minimal residual disease (MRD), and the advent of novel targeted agents with impressive efficacy prompted an international panel to provide updated recommendations. These guidelines were recently published and include a revised version of the iwCLL response criteria, an update on the use of the MRD status in the clinical context, and recommendations regarding the assessment and prophylaxis of viral diseases during the management of CLL.

Response assessment in pediatric neuro-oncology presents unique challenges compared to adult practice. In fact the majority of pediatric tumors are of low grade and can have rather indolent courses with both contrast enhancing and nonenhancing components, often not easily measurable, compared to the adult population where most of the tumors are high-grade gliomas.

Response assessment is the clinical, biopathological, and radiological evaluation of disease at an interim time point during treatment or at the end of the therapy to determine and evaluate the success of therapy. Response determination during therapy for non-Hodgkin lymphoma is important because intensification of therapy for those with residual disease has been proven to be beneficial in some tumor types. Histological confirmation remains the gold standard to differentiate active residual disease from tumor necrosis or inflammatory scar tissue and allows for the application of highly sensitive techniques such as immunophenotyping by flow cytometry, cytogenetics and FISH analysis, and molecular PCR methods. Conventional cross-sectional imaging modalities such as CT are appealing for its ability to assess the entire tumor, is widely available and minimally invasive. Functional imaging with FDG-PET, though not available at all centers, has become an invaluable tool in staging and response assessment, but its role remains unclear and needs to be further evaluated in pediatric NHL. As pediatric NHL is well recognized to be a different spectrum of disease than adult NHL, the need for separate pediatric criteria led to a multidisciplinary collaboration resulting in the development of the International Pediatric NHL Response Criteria. Future use and adoption of these standardized criteria will allow for comparison of treatment efficacy across multiple regimens and improve clinical decision-making.

In the last few years formidable progress has been made in the field of breast imaging, the leading malignancy in women. Clinicians find it difficult to keep pace with the new techniques, the specifications and indications of each and the selection of the right one for the problem they face. At times it is also hard to interpret the findings into meaningful clinical action. The selection is also complicated by matters of availability, cost in relation to benefit, and whether the result is going to alter the treatment plan. In this chapter, an effort is made to outline the clinical component of the breast imaging studies in diagnosis, staging, operative planning, post-operative follow-up, and post-treatment response assessment. Important factors that emerge are the woman’s accurate risk calculation, the understanding of the BI-RADS classification, the adherence to guidelines, the adoption of evidence-based practices, and the close cooperation with the imaging colleagues.

In the past few years, formidable progress has been made in the field of breast imaging, the leading malignancy in women. Clinicians find it difficult to keep pace with the new techniques, the specifications and indications of each, and the selection of the right one for the problem they face. At times, it is also hard to interpret the findings into meaningful clinical action. The selection is also complicated by matters of availability, cost in relation to benefit and whether the result is going to alter the treatment plan. In this chapter, an effort is made to outline the clinical component of the breast imaging studies in diagnosis, staging, operative planning, postoperative follow-up, and posttreatment response assessment. Important factors that emerge are the woman’s accurate risk calculation, the understanding of the BI-RADS classification, the adherence to guidelines, the adoption of evidence-based practices, and the close cooperation with the imaging colleagues.

Analyses of the stigma associated with mental patients have been exhaustively developed. Some of these analyses refer to the general population in different countries, some others compare conclusions from these countries, and some others discuss the attitutes of either current or future (psychiatric and non-psychiatric) health professionals with respect to mental illness. Most of the studies are based on well-known questionnaires (usually on their country-adapted versions), each of them corresponding to a multi-item scale evaluated using either a 5-, 6- or 7-point Likert scale and focussing on different attitudinal factors or constructs. This paper introduces a quite preliminary study in this setting, aiming to examine the influence of the medical specialty on the perception about mental patients and involving a more expressive and flexible scale to rate attitudes: the fuzzy rating scale (allowing a free fuzzy set-valued response assessment to items).

PET/CT has a key role in final response assessment after treatment in most types of malignant lymphomas, as well as in baseline staging and interim (mid-treatment) evaluation. Its application is widely established in Hodgkin lymphoma (HL) and aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMLBCL), and other related subtypes. Although recent recommendations suggest the use of PET/CT for baseline staging and response assessment in follicular lymphomas, mantle cell lymphoma (MCL), Burkitt lymphoma, and “nodal” T-cell lymphomas [anaplastic large cell (ALCL), peripheral T-cell (PTCL), and angioimmunoblastic T-cell lymphoma (AITL)], the accumulated clinical experience with these subtypes is considerably less. The role of PET/CT is much more controversial in non-follicular low-grade lymphomas and primary extranodal lymphomas other than DLBCL.