Tumor Response Criteria Research Articles

INVITED REVIEW—NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.

Comparison of Response Evaluation in Patients with Gastroenteropancreatic and Thoracic Neuroendocrine Tumors After Treatment with [177Lu-DOTA0,Tyr3]Octreotate

Response Evaluation Criteria In Solid Tumors (RECIST) (unidimensional), Southwest Oncology Group (SWOG) solid tumor response criteria (bidimensional), and their modified variants are commonly used in the tumor response assessment after treatment of gastroenteropancreatic and thoracic neuroendocrine tumors (NETs). In the current study, RECIST, SWOG criteria, modified RECIST (mRECIST), and modified SWOG (mSWOG) criteria were compared in patients with NETs treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). Two-hundred sixty-eight Dutch patients with NETs who had been treated with (177)Lu-octreotate between January 2000 and April 2007 were studied. CT or MR imaging scans were analyzed using RECIST, SWOG criteria, mRECIST, and mSWOG criteria (including the tumor response class minor response [decrease of 13%-30% for mRECIST and 25%-50% for mSWOG]). The outcomes were correlated with progression-free survival (PFS) and overall survival (OS). Eleven patients had an unknown tumor response and were excluded. The rates of objective response (OR) (complete response + partial response [+minor response for mRECIST/mSWOG]), stable disease, and progressive disease (PD) were 28%, 49%, and 24%, respectively, according to RECIST; 25%, 49%, and 26%, respectively, according to SWOG; 44%, 33%, and 24%, respectively, according to mRECIST; and 45%, 29%, and 26%, respectively, according to mSWOG. In patients who had OR, stable disease, or PD, the median PFS was 26-30, 27-34, and 8 mo, respectively, with any of the 4 response criteria. In patients who had OR, stable disease, or PD, the median OS was 55-57, 56-74, and 11-12 mo, respectively, with any of the 4 response criteria. Subanalyses for patients who had progression before treatment start were comparable. Patients with PD as treatment outcome had significantly shorter PFS and OS than patients with an OR or stable disease with all 4 scoring systems. PFS and OS were comparable for patients with tumor regression and stable disease. The addition of the response class minor response did not improve the correlation with PFS and OS. The 4 scoring systems gave comparable results in terms of PFS and OS per categorized outcome.

An Update on Criteria for Assessing Tumor Response to Treatment

Standardized tumor response criteria have been developed over time since the advent of cytotoxic anticancer therapies. The criteria have evolved and continue to do so as the understanding of the therapeutic basis of various anticancer agents increases and as novel therapeutic agents are developed. Currently, the criteria can be divided into the following main categories: anatomical-based criteria; tumor- and therapy-specific criteria; metabolic-based criteria; and response assessment of lymphomas. The standardized criteria are critical to the successful conduct of clinical trials during the development of cancer therapeutic agents as they offer uniform end points that facilitate comparison of therapeutic agents and interpretation of studies. The criteria are also relevant in clinical practice as they standardize how radiologists select, measure, and report lesions in oncology patients, and they provide standardized definitions for tumor response categories. To remain relevant in a rapidly evolving oncology field and provide up-to-date imaging information that meets the needs of oncologists in both research trials and clinical practice, radiologists need to familiarize themselves with the various standardized tumor response criteria.

Molecular targeted therapies in non-GIST soft tissue sarcomas: what the radiologist needs to know.

Non-gastrointestinal stromal soft tissue sarcomas are uncommon neoplasms that have a dismal prognosis due to a high incidence of metastases and a poor response to conventional chemotherapy. The identification of characteristic genetic alterations in several of these tumors has opened the window for molecular targeted therapies in patients who have failed conventional chemotherapy. Imaging plays a critical role in assessing the response to these novel therapeutic agents. Just like the response of gastrointestinal stromal tumors to imatinib, the response of non-gastrointestinal stromal soft tissue sarcomas to molecular targeted drugs is better evaluated on imaging by alternate tumor response criteria such as the Choi criteria. In addition, these drugs are associated with distinct class-specific drug toxicities that can come to attention for the first time on imaging. The purpose of this article is to provide a primer for the radiologist on the various molecular targeted therapies in advanced/metastatic non-gastrointestinal stromal soft tissue sarcomas with emphasis on the role of imaging in assessing treatment response and complications.

Tumor response evaluation criteria for HCC (hepatocellular carcinoma) treated using TACE (transcatheter arterial chemoembolization): RECIST (response evaluation criteria in solid tumors) version 1.1 and mRECIST (modified RECIST): JIVROSG-0602

Background.Two standard sets of criteria are used to evaluate the tumor response of hepatocellular carcinoma (HCC): RECIST (Response Evaluation Criteria in Solid Tumors) and modified RECIST (mRECIST). The purpose was to compare two tumor response evaluation criteria, RECIST version 1.1 and mRECIST, for HCC treated using transcatheter arterial chemoembolization (TACE).Methods.The radiological findings of patients who underwent TACE for HCCs in a multicenter clinical trial were examined. Sixty-five lesions in 21 patients treated with TACE without mixing iodized-oil were evaluated. The tumor size was evaluated by measuring the entire lesion, including the necrotic part, using RECIST version 1.1, whereas only the contrast-enhanced part observed during the arterial phase was measured using mRECIST. Five radiologists independently measured each lesion twice. To evaluate the inter-criteria reproducibility, the complete response (CR) rate, the response rate, the kappa statistics, and the proportion of agreement (PA) for response categories were calculated. The same analyses were conducted for inter- and intra-observer reproducibility.Results. In the inter-criteria reproducibility study, the CR rate and the response rate obtained using mRECIST (56.9% and 79.7%) were higher than those obtained using RECIST version 1.1 (9.2% and 43.1%). In the inter- and intra-observer reproducibility study, mRECIST exhibited an ‘almost perfect agreement', while RECIST version 1.1 exhibited a ‘substantial agreement'.Conclusions. Considerable differences in the CR rate and the response rate were observed. From the viewpoint of the high inter- and intra-observer reproducibility, mRECIST may be more suitable for tumor response criteria in clinical trials of TACE for HCC.

Genitourinary Imaging: Part 2, Role of Imaging in Medical Management of Advanced Renal Cell Carcinoma

Renal cell carcinoma (RCC) comprises 80-85% of all primary renal neoplasms. Knowledge of the genetic and molecular features of RCC and the advent of molecular targeted therapy have revolutionized the treatment of RCC in the past decade. This article will review the changing role of the radiologist in the management of advanced RCC, especially in terms of the new relevance of RCC subtypes, treatment-related changes on imaging, new tumor response criteria, and commonly encountered molecular targeted therapy-related toxicities. In this era of personalized cancer treatment, imaging has assumed a central role in treatment selection and follow-up of advanced RCC.

A Prospective Study of Bone Tumor Response Assessment in Metastatic Breast Cancer

BackgroundIn our previous study, new MD Anderson (MDA) bone tumor response criteria (based on computed tomography [CT], plain radiography [XR], and skeletal scintigraphy [SS]) predicted progression-free survival (PFS) better than did World Health Organization (WHO) bone tumor response criteria (plain radiography [XR] and SS) among patients with breast cancer and bone-only metastases. In this pilot study, we tested whether MDA criteria could reveal bone metastasis response earlier than WHO criteria in patients with newly diagnosed breast cancer with osseous and measurable nonosseous metastases. MethodsWe prospectively analyzed bone metastasis response using each imaging modality and set of bone response criteria to distinguish progressive disease (PD) from non-PD and their association with PFS and overall survival (OS). We also compared the response of osseous metastases assessed by both criteria with the response of nonosseous measurable lesions. ResultsThe median follow-up period was 26.7 months (range, 6.1-53.3 months) in 29 patients. PFS rates differed at 6 months based on the classification of PD or non-PD using either set of criteria (MDA, P = .002; WHO, P = .014), but these rates, as well as OS, did not differ at 3 months. Response in osseous metastases by either set of criteria did not correlate with the response in nonosseous metastases. ConclusionMDA and WHO criteria predicted PFS of patients with osseous metastases at 6 months but not at an earlier time point. We plan a well-powered study to determine the role of MDA criteria in predicting bone tumor response by incorporating 18-fluorodeoxyglucose (18F) positron emission tomography (FDG-PET)/CT to see if findings using this modality are earlier than those with WHO criteria.

1480PD - Efficacy and Safety of Denosumab in Giant Cell Tumor of Bone: Updated Results with Independent Radiographic Assessment of Response

ABSTRACT Giant cell tumor of bone (GCTB) is an aggressive osteolytic tumor that causes substantial morbidity. We present data from a second open label phase 2 study of denosumab in GCTB. Patients (pts) with surgically unresectable GCTB (Cohort 1), resectable GCTB with planned surgery (Cohort 2), and pts who transferred from the first phase 2 study (Cohort 3) received SC denosumab (120 mg, Q4W), with additional doses on days 8 and 15 (Cohorts 1–2). Prespecified efficacy and safety analyses included all pts who received denosumab. Radiographic assessments of tumor response included pts with ≥1 evaluable time point response (TPR); assessments included RECIST (lesion size), EORTC (PET Standardized Uptake Value by Body Weight [SUVbw]), and Density/Size (CT Hounsfield units). Pts (N = 282) were 58% women, mean age 36 (SD 13) years; 46% had recurrent unresectable disease. AEs were reported in 236 pts (84%); most frequent were arthralgia 20%; headache 18%; nausea 17%; fatigue 16%; back pain 15%; and extremity pain 15%. Osteonecrosis of the jaw was reported in 3 pts (1%). One pt died of respiratory failure, not denosumab-related. Hypocalcemia was reported in 15 pts (5%): 14, grade 1 or 2; 1, grade 3 not deemed clinically significant by the investigator. Of 100 pts in Cohort 2, 90% had no surgery or less morbid surgery than planned. Radiologic analyses included 190 pts. An objective complete or partial tumor response was observed in 72% of pts based on best response, any criteria. Of pts with ≥1 objective tumor response, response rates were 25% with RECIST, 96% with EORTC, and 76% with Density/Size criteria. Among pts with ≥1 evaluable TPR, the median time to objective tumor response was 3.1 months (95% CI 2.89, 3.65) based on best response using any tumor response criteria. Among pts with ≥2 evaluable TPRs ≥12 weeks apart, 96% had tumor control sustained ≥12 weeks based on the best response using any tumor response criteria. Eleven pts (6%) had disease progression. Conclusion: Denosumab appeared to be well tolerated in pts with GCTB, reduced requirements for morbid surgery, and provided a durable objective radiologic response for the majority of pts. Denosumab continues to be studied as a potential treatment for GCTB. Disclosure J. Blay: JY Blay has served as an advisory board member for Novartis, GSK, Roche, MSD, and Pharmamar. He has conducted corporate-funded research for Novartis, GSK, Roche, MSD, and Pharmamar. S. Chawla: Sant Chawla has been an advisory board member for and has received corporate-sponsored research funding from Amgen, Threshold, Cytrax, Glaxxo, and Berg Pharma. E. Choy: E. Choy has served as an advisory board member for Amgen, Sanofi-Aventis, and Biomed Valley Discoveries. S. Ferrari: S. Ferrari has received funds from: AMGEN, MOLMED, PharmaMar, and Pfizer. He received funds for participation to scientific meetings from Takeda. P. Reichardt: P. Reichardt has received honoraria for lectures from Amgen Inc. P. Rutkowski: P. Rutkowski has served as an advisory board member for Norvartis, BMS, and MSD. He has also received honoraria for lectures and travel grants from Novartis, Pfizer, Roche, BMS, and MSD. D. Thomas: David Thomas conducts corporate-sponsored research with Pfizer and AMGEN. Y. Qian: Y. Qian is an employee and stockholder of Amgen Inc. I. Jacobs: I. Jacobs is an employee and stockholder of Amgen Inc. All other authors have declared no conflicts of interest.

1000P - Neoadyuvant Chemotherapy Followed by Chemorradiation in Locally-Advanced Squamous Cervical Cancer

ABSTRACT Introduction Although there has not been a direct comparison between neoadjuvant chemotherapy followed by chemor-radiation with the standard treatment of concurrent chemor-radiation, neoadjuvant chemotherapy is active in squamous cervical cancer. Material and methods In this open label 1 arm phase two trial we accrued 19 patients from 2007 to 2011 diagnosed with squamous cervical cancer deemed to be unresectable and poor candidates to concurrent chemor-radiation. Patients had to be over 18 years of age, give informed consent, have a PS0-1 and adequate organ function. They received neoadjuvant chemotherapy with paclitaxel 80mg/m2 and cisplatin33mg/m2 days 1,7,15/28 for two cycles and then external radiation in 1.8 Gy/ fraction with concurrent cisplatin 40mg/m2/weekly followed by brachytherapy in 5-6 applications. After completion of neoadjuvant treatment and after concurrent chemor-radiation patients were evaluated by RECIST 1,1 criteria for tumor response with a CT scan and pelvic MNR and data of dose intensity and toxicity was accrued. Results Median age at diagnosis was 51 years (27 to 72 years); all the patients had PS1 due to local pain, asthenia or genital discharge. Neoadjuvant treatment was feasible in all patients with manageable toxicities; the dose intensity delivered was 97% of the preplanned dose. Only 2 episodes of grade III anemia were observed. In the first radiologic evaluation 4 patients had a complete response, 12 had partial response and 3 disease stabilization. Patients received external radiotherapy in fractions of 1.8 Gy achieving a dose of 66 GY in patients that could not receive brachytherapy. Mean EQD2C for those who did (68%) was 72 GY. Only 68% of the patients received the full preplanned concomitant dose due to toxicity, mainly grade III anemia and diarrhea. In the second radiological evaluation 9 patients had a complete response, 9 partial and only 1 stable disease. At a mean of 24 months of follow up only 5 patients (26%) thus far have developed recurrent disease, all of the recurrences were simultaneously local as well as systemic. Conclusion Our weekly cisplatin-paclitaxel regimen has been demonstrated to be feasible and effective in terms of dose delivery, tolerance and radiological responses without compromising definitive treatment with chemor-radiation. Disclosure All authors have declared no conflicts of interest.

Tumor Response Criteria: Are They Appropriate?

Tumor Response Criteria: Are They Appropriate?

Measurement of Circulating Cell‐Free DNA in Relation to 18F‐Fluorocholine PET/CT Imaging in Chemotherapy‐Treated Advanced Prostate Cancer

Purpose: To examine the effects of chemotherapy on circulating cell‐free DNA (cfDNA) composition in relation to investigational whole‐body measurement of tumor activity by fluorine‐18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in hormone‐refractory prostate cancer (HRPC). Methods: Serial FCH PET/CT scans were performed in eight patients with HRPC receiving docetaxel‐based chemotherapy. Corresponding serial cfDNA samples were characterized by microfluidic electrophoresis, quantified by real‐time PCR, and compared with PET/CT results. Promoter methylation of two prostate cancer‐associated genes, GSTP1 and RARB2, was assessed by methylation‐specific PCR of bisulfite‐converted cfDNA. Results: Plasma cfDNA concentrations increased significantly from 13.3 ng/mL at baseline to 46.8 ng/mL and 50.9 ng/mL after one and three treatment cycles, respectively (p= 0.001). GSTP1 and/or RARB2 promoter methylation was identified in all pretreatment samples. The appearance of large (200 bp–10.4 kb) cfDNA fragments was noted in posttreatment samples along with loss of methylation at GSTP1 and/or RARB2. Tumor activity on PET/CT correlated with cfDNA concentration (r=−0.50, p= 0.01). Patients meeting criteria for PET tumor response had significantly lower pretreatment cfDNA levels than those who did not (8.0 vs. 16.4 ng/mL, p= 0.03). Conclusions: Chemotherapy is associated with significant changes in plasma cfDNA content and FCH PET/CT‐detected tumor activity. These interrelated measures are potential candidate markers of therapeutic response in HRPC. Clin Trans Sci 2012; Volume #: 1–6

CT findings of response and recurrence, independent of change in tumor size, in colorectal liver metastasis treated with bevacizumab.

The purpose of this article is to provide a practical review of newly established morphologic tumor response criteria for hepatic colorectal metastasis treated with bevacizumab-containing chemotherapy and a description of the patterns of early recurrence. We also discuss the respective value of these criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). RECIST alone are not sufficient to assess response after bevacizumab-containing chemotherapy for hepatic colorectal metastasis. The combined use of RECIST and morphologic criteria is mandatory for optimal evaluation in this population.

Radiologic Aspects of Immune-Related Tumor Response Criteria and Patterns of Immune-Related Adverse Events in Patients Undergoing Ipilimumab Therapy

The objective of this article is to illustrate examples of radiologic immune-related response criteria and toxicity in patients with advanced melanoma treated with the immunotherapeutic agent ipilimumab. Novel immune-related tumor response criteria should be applied to patients undergoing therapy with ipilimumab for advanced melanoma. Ipilimumab also produces a spectrum of immune-related adverse effects that can be recognized radiologically.

Chemotherapy Definitions and Policies for Thymic Malignancies

Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat.1 Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection, which is the mainstay of the curative-intent treatment.1 However, approximately 30% of patients present with an advanced tumor at the time of diagnosis, with invasion of neighboring organs, dissemination to the pleura, the pericardium, or less frequently extrathoracic organs. In such cases, chemotherapy has been used both to reduce the tumor burden—possibly allowing subsequent surgery or radiotherapy—and to achieve prolonged disease control. Recurrence after resection may be similarly treated with chemotherapy. Thymic carcinomas, although rare, are usually already advanced at the time of presentation, and systemic therapy is important for almost all of these patients. Knowledge regarding chemotherapy for thymic tumors has mainly been based on retrospective series,2–9 although several prospective trials have also been conducted.10–21 These studies have clearly demonstrated the chemosensitivity of thymoma, and to a lesser extent thymic carcinoma, to various cytotoxic agents and combinations. However, details of patient selection are often lacking (either disease extent or general condition), and the intent of the treatment sequence is often vague. Adoption of a common language and definition of terms is crucial for the International Thymic Malignancies Interest Group (ITMIG) effort to develop a international prospective database of thymic tumors. The article by Huang et al.22 provides definitions for survival and endpoints for recurrences assessment and discusses how to measure response to treatment. Herein, we discuss additional points with regard to chemotherapy, including treatment sequence, general modalities, and impact of corticosteroids.

Neuroradiological Response Criteria for High-grade Gliomas

The recently introduced new response criteria of the response assessment in neuro-oncology (RANO) working group and its clinical implications are the topic of this article. Establishing this working group as a work-in-progress platform and its first report, the RANO criteria represent an important step forward in the accurate assessment of response to therapy in patients with malignant gliomas not only in clinical trials but also in daily practice. Anti-angiogenic therapy and other new treatment modalities have increased the incidence and awareness of novel imaging phenomena, such as pseudoprogression and pseudoresponse not only within clinical trials. The new RANO criteria also take clinical parameters, such as steroid medication and neurological symptoms into account. Neuroradiologists and neuro-oncologists need to be aware of and experienced in applying these new criteria to correctly assess the response to treatment in patients with malignant gliomas. Further research is needed to study new imaging techniques, such as perfusion and diffusion-weighted imaging and to investigate and incorporate these for routine tumor response criteria.

Measurement of tumor size in adult glioblastoma: Classical cross-sectional criteria on 2D MRI or volumetric criteria on high resolution 3D MRI?

ObjectiveTo investigate the added value of volume on post-contrast three dimensional (3D) T1-weighted image (T1WI) over classical cross-sectional area on two dimensional (2D) T1WI in evaluating tumor response in glioblastoma multiforme (GBM). MethodsTumor cross-sectional area and volume measurements were performed on 104 MRI studies from 42 adult patients with GBM on post-contrast 5mm 2D T1WI and isotropic high resolution 3D T1WI, respectively. 52 pairs of MRI scans were analyzed for relative change. Radiographic responses were determined based on change in either area or volume. ResultsA high correlation was revealed between tumor size measured by area on thick 2D and volume on high resolution 3D MRI in 104 scans (r=0.82, p<0.001). When four tumor response criteria were used according to the percentage changes (complete response/partial response/stable disease/progression), the kappa coefficient between the area on 2D and volume on 3D was 0.68 (p<0.05) with an overall agreement of 81%. ConclusionsTumor cross-sectional area on post-contrast 2D T1WI appears comparable to volume on 3D T1WI and should still be a practical alternate of volume on 3D for evaluating tumor response.

Randomized phase II study of the efficacy and safety of gemcitabine plus TH-302 versus gemcitabine alone in previously untreated patients with advanced pancreatic cancer.

TPS176 Background: A hypoxic microenvironment is believed to be a characteristic of solid tumors including pancreatic adenocarcinoma (PAC) and is associated with resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to specifically target the hypoxic microenvironment. Combining gemcitabine (G) with TH-302 may enable the targeting of both the normoxic and hypoxic regions of PAC. TH-302 was investigated in combination with full-dose G as part of a phase I/II study and the efficacy of the combination was higher than generally reported with single agent G (Burris, JCO 1997). 43 PAC patients received 1000 mg/m2 G in combination with 240 – 575 mg/m2 TH-302. By RECIST tumor response criteria, 1 (2%) had a CR, 8 (19%) had a PR, 39 (91%) patients had SD or better. Median PFS and OS were 5.95 and 8.5 months, respectively. Based upon these data, an ongoing randomized study (NCT01144455) is being conducted to assess the benefit of adding TH-302 to the standard dose G regimen for first-line therapy of PAC. Methods: An open-label multi-center Phase II study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone was initiated in June 2010. Patients are randomized at a ratio of 1:1:1. TH-302 is administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. G (1000 mg/m2) is administered IV over 30 minutes on Days 1, 8 and 15 starting 2 hours after completion of the TH-302 infusion when used in combination. Patients on the G arm who discontinue for disease progression and meet eligibility may crossover and be randomized to a TH-302 plus G arm. Key eligibility criteria: locally advanced unresectable or metastatic PAC untreated with chemotherapy, ECOG status 0 or 1, measurable disease by RECIST and adequate hematologic, hepatic and renal function. The primary efficacy endpoint is a progression-free (PFS)/event-free (EFS) comparison of the combination arms vs G alone. Interim analyses for efficacy and safety are scheduled after approximately 50, 75 and 100 PFS or EFS events. Additional analyses comparing each of the two TH-302 dose levels with G versus the G alone arm will also be conducted. Over 90 of 165 planned patients have been enrolled.

Radiologists Urge FDA To Accept PET-Based Tumor Response Criteria in Clinical Trials

Radiologists Urge FDA To Accept PET-Based Tumor Response Criteria in Clinical Trials

Restoration of tumor equilibrium after immunotherapy for advanced melanoma

Metastatic melanoma runs a predictable detrimental course in the vast majority of patients. New modalities of immunotherapy, such as melanoma antigen-specific therapeutic vaccination and cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor blockade by monoclonal antibodies (mAbs), have been associated with atypical kinetics of tumor response that differ from those observed during cytotoxic treatment. Recently, new tumor response criteria have been proposed based on the tumor response characteristics observed in clinical studies with ipilimumab (the so-called 'immune-related response criteria'). We report three illustrative cases of the American Joint Committee on Cancer stage IV-M1c melanoma patients who experienced atypical kinetics of tumor response to the treatment with the CTLA-4-blocking mAb, ipilimumab (case 1), or an autologous dendritic cell vaccine in combination with interferon α-2b (cases 2 and 3). These cases show that atypical response patterns not only relate to the outcome of CTLA-4-blocking mAb therapy but also to the treatment with therapeutic vaccines and interferon α-2b.

Radiologische Evaluation des Tumoransprechens in onkologischen Therapiestudien (Tumor Response Evaluation)

Radiological-morphological response evaluation plays a major role in oncological therapy and studies for approval. Specific criteria have been developed for some tumor entities and chemotherapeutics. Application, limitations and definitions of the most frequently used criteria for tumor response evaluation will be presented. Review based on a selective literature research. In clinical oncological therapy studies, WHO and RECIST are the most frequently used criteria to evaluate morphological therapy response. RECIST criteria have been modified recently, especially with respect to the evaluation of lymph nodes, and were published as RECIST 1.1 in 2009. All criteria were originally developed and defined to review clinical multicenter trials for approval. Using these criteria in a clinical situation, certain limitations have to be considered. To evaluate response, a baseline scan before therapy start is mandatory. Special tumor response criteria have been defined for some certain tumor entities. Oncologists and radiologists should define in advance which criteria are used before starting therapy. The use of defined criteria is very important in oncology response evaluation. In-depth knowledge of the criteria and their limits is required for correct usage.