Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review.

Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source, thus limiting its effects to the site of delivery. However, the off-target diversion of yttrium-90 microspheres to tissues other than the tumor may lead to complications. The most prominent of these complications include radiation gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radioembolization-induced liver disease, which may occur despite careful pretreatment planning. Thus, selective internal radiation therapy demands an expert multidisciplinary team approach in order to provide comprehensive care for patients. This review provides recommendations to multidisciplinary teams on the optimal medical processes in order to ensure the safe delivery of selective internal radiation therapy. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis, and management of potential radiation injury to the liver and to other organs. (Hepatology 2017;66:969-982).

Monitoring metabolic response using FDG PET-CT during targeted therapy for metastatic colorectal cancer.

INTRODUCTION: The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient's unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine. METHODS: This substudy was performed within the framework of a wider prospective multicenter study on the predictive value of early FDG PET-CT response assessment (SoMore study). A lesion-based response analysis was performed, including all measurable lesions identified on the baseline PET. On a per-patient basis, a descriptive 4-class response categorization was applied based upon the presence and proportion of non-responding lesions. For dichotomic response comparison, all patients with at least one resistant lesion were classified as non-responding. RESULTS: On baseline FDG PET-CT, 124 measurable "target" lesions were identified in 38 patients. Early mR assessments showed 18 patients (47 %) without treatment resistant lesions and 12 patients (32 %) with interlesional response heterogeneity. The NPV and PPV of early mR were 85 % (35/41) and 84 % (70/83), respectively, on a per-lesion basis and 95 % (19/20) and 72 % (13/18), respectively, on a dichotomized per-patient basis. CONCLUSIONS: Early mR assessment performed after one cycle of sorafenib-capecitabine in mCRC is highly predictive of non-response at a standard response assessment time. The high NPV (95 %) of early mR could be useful as the basis for early treatment discontinuation or adaptation to spare patients from exposure to non-effective drugs.

Phase II trial evaluating the efficacy of sorafenib (BAY 43-9006) and correlating early fluorodeoxyglucose positron emission tomography-CT response to outcome in patients with recurrent and/or metastatic head and neck cancer.

BACKGROUND: The purpose of this study was to assess the efficacy and safety of sorafenib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) and to explore the predictive value of early metabolic responses. METHODS: Sorafenib was administered orally at 400 mg bid on a continuous basis. The primary endpoint was the response rate. Correlation of early (18)fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT response to time-to-event outcomes was a secondary objective. RESULTS: Twenty-three patients were included in this study. Grade 3 to 4 toxicities included fatigue (22%), hand-foot syndrome (9%), lymphopenia (17%), hyponatremia (39%), and hypophosphatemia (48%). One patient (5%) had a partial response (PR) and 12 patients (55%) had stable disease. Early metabolic response rate was 38%. Median progression-free survival (PFS) was 2.2 months in early metabolic nonresponders (13 of 21 patients) in comparison to 7.4 months in the 8 patients with class I early metabolic response (p = .006). CONCLUSION: Sorafenib showed a modest antitumor activity. Data suggest a possible role of (18)FDG PET metabolic response as an early predictor of a prolonged PFS.

Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study.

BACKGROUND: Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available. METHODS/DESIGN: PePiTA is a prospective, multicenter, non-randomised trial built on the hypothesis that preoperative chemosensitivity testing using FDG-PET/CT before and after one course of FOLFOX can identify the patients who are unlikely to benefit from 6 months of adjuvant FOLFOX treatment for stage III colon cancer. DISCUSSION: PePiTA is the first study to use the primitive tumor chemosensitivity assessed by metabolic imaging as a guidance for adjuvant therapy in colon cancer. It could pave the way for tailoring the treatment and avoiding useless toxicities for the patients and inadequate expenses for the society. It could also give an interesting insight into tumoral heterogeneity, resistance to chemotherapy, genetic predisposants to oxaliplatin toxicity and immune response to cancer. EUDRACT NUMBER: 2009-011445-13 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00994864.

Role of positron emission tomography in the management of head and neck cancer in the molecular therapy era.

PURPOSE OF REVIEW: The utility of positron emission tomography-computed tomography has increasingly been studied during the last years. Positron emission tomography-computed tomography offers a holistic approach of cancer diagnosis as it can integrate structural, functional, metabolic, and molecular information of tumour. The technique offers three-dimensional, high-resolution, whole body, and quantitative imaging. 18F-Fluoro-2-deoxy-D-glucose still remains the only tracer widely available. Other tracers have been designed for assessment of proliferation, amino acid uptake, and hypoxia. RECENT FINDINGS: 18F-Fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography seems the most appropriate technique for the assessment of locoregional lymph node involvement in head and neck cancer. False negativity of positron emission tomography-computed tomography in case of micrometastatic lymph node disease should be compensated by the implementation of the sentinel node scintigraphy guided biopsy. 18F-Fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography has a very high sensitivity and negative predictive value in detecting residual disease after radiotherapy or early recurrent disease. Radiotherapy planning can use the 18F-fluoro-2-deoxy-D-glucose uptake distribution for increasing the accuracy of delineation of the target volumes in conformal radiotherapy. Positron emission tomography-computed tomography with other tracers such as deoxy-18F-fluorothymidine for proliferation mapping and [F-18] fluoromisonidazole for hypoxia mapping are currently being studied. SUMMARY: Major studies have now confirmed the utility of positron emission tomography-computed tomography in the different phases of diagnostic and therapeutic phases of the management of patients with head and neck cancer.