3-T magnetic resonance-guided high-intensity focused ultrasound (3 T-MR-HIFU) for the treatment of pain from bone metastases of solid tumors.

INTRODUCTION: Bone metastases (BM) are still the main cause of morbidity and mortality in cancer patients, not only because of their complications, defined as skeletal-related events (SREs), but also because of the negative impact bone pain has on quality of life (QoL) and survival, especially when opioid analgesics and locoregional treatments fail. MATERIALS AND METHODS: A single-center prospective study was carried out on 12 patients with symptomatic BM treated with MRI-guided focused ultrasound (MR-HIFU). The primary endpoint was the effectiveness of MR-HIFU in reducing current and breakthrough cancer pain (BTCP) scores. The main secondary aims were the evaluation of circulating markers at different time-points and their relation to pain and procedure efficacy. Other secondary objectives included temporal evolution of pain response, evaluation of QoL, and side effects of the treatment. Descriptive statistics were used to evaluate primary and secondary endpoints. Questionnaires on pain and QoL completed at baseline and at 30 days were compared using appropriate statistical tests with exploratory intent. RESULTS: MR-HIFU was successfully completed in all 12 patients enrolled between September 2015 and December 2018. On day 30, 6 (50.0%) patients showed a complete response of current pain and 6 a partial response, while 5 (41.7%) obtained a complete BTCP response. A partial response of BM evaluated by MD Anderson criteria was obtained in 9 (81.8%) patients. Only one patient progressed in the target lesion after MR-HIFU. No treatment-related adverse events were recorded. Bone turnover markers CTX/RANK-L (P) do not demonstrate any significant change with the pain or BM response. CONCLUSION: In our patients, targeted therapy of painful BM with MRI-guided focused ultrasound ablation was safe and showed encouraging early-onset and functional results.

Taxanes as a risk factor for acute adverse reactions to iodinated contrast media in cancer patients.

BACKGROUND: The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. METHODS: We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. RESULTS: Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74-1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14-2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02-4.16). CONCLUSION: Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs.

Does the time between CT scan and chemotherapy increase the risk of acute adverse reactions to iodinated contrast media in cancer patients?

BACKGROUND: Cancer patients undergo routine computed-tomography (CT) scans and, therefore, iodinated contrast media (ICM) administration. It is not known whether a time-dependent correlation exists between chemotherapy administration, contrast enhanced CT and onset of acute ICM-related adverse reactions (ARs). METHODS: All consecutive contrast-enhanced CTs performed from 1 January 2010 to 31 December 2012 within 30 days of the last chemotherapy administration were retrospectively reviewed. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. We analyzed time to CT evaluation calculated as the time elapsed from the date of the CT performed to the date of the last chemotherapy administration. Patients were classified into 4 groups based on the antineoplastic treatment: platinum-based, taxane-based, platinum plus taxane and other group. RESULTS: Out of 10,472 contrast-enhanced CTs performed, 3,945 carried out on 1,878 patients were considered for the study. Forty acute ICM-related ARs (1.01%; 95% CI, 0.70-1.33) were reported. No differences were seen among immediate (within 10 days of the last chemotherapy administration), early (11-20 days) and delayed (21-30 days) CTs. Median time to CT in patients who experienced an acute ICM-related AR by treatment group was not statistically different: 20 days (range 6-30), 17 days (range 5-22), 13 days (range 8-17), 13 days (range (2-29) for the platinum, taxane, platinum plus taxane and other group, respectively (P =0.251). CONCLUSIONS: Our results did not reveal any correlation between time to CT and risk of acute ICM-related ARs in cancer patients.

Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma.

High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up to 4 cycles, thereafter every 4 weeks for a maximum of 2 cycles. The primary endpoint was the immunological efficacy of the combined RT/HD IL-2 treatment (assessed by IFN-γ ELISPOT). Nineteen out of 22 patients were evaluable for immunological and clinical response. Partial response occurred in 3 (15.7%) patients and stable disease was observed in 7 (36.8%). The disease control rate was 52.6% after a median follow up of 39.2 months. According to Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), the majority of toxicities were grade 1-2. Immunological responses were frequent and detected in 16 (84.2%) patients. Increased levels of IL-8 and IL-10 in melanoma, circulating effector memory CD4+ and intratumoral CD8+ T cells in both tumor types were detected after therapy. Overall the treatment was well tolerated and immunologically active. Immunomonitoring and correlative data on tumor and peripheral blood cell subsets suggest that this combination treatment could be a promising strategy for patients progressing after standard treatments.

Increased frequency of acute reactions to iodinated contrast media in cancer patients treated with anti-CTLA-4 immunomodulatory antibodies.

Contrast-enhanced computed tomography (CECT) is an indispensable tool in the management of cancer patients. However, this procedure can be complicated by the development of acute adverse reactions (ARs) to iodinated contrast media (ICM). On the basis of the hypothesis that cancer immunotherapy, in particular with immune checkpoint inhibitors, increases the incidence of allergic-like immediate ARs to ICM with respect to "standard" cancer chemotherapy/targeted therapy (CHT) we retrospectively evaluated the incidence of CECT-related immediate ARs in cancer patients undergoing cancer treatments. All patients who underwent at least one CECT scan after starting any cancer treatment between 2006 and 2014 were included in a mono-institutional radiological database. The staff of the Radiology Unit recorded any ARs that occurred within 30 min of the ICM injection and classified them as "allergic-like" or "physiologic" and graded as mild, moderate, or severe according to the American College of Radiology (ACR) Manual on Contrast Media, version 10.1. Fifty-nine of the 3,521 patients included in the database received ipilimumab (Ipi), 75 received cytokines (Cys), and the remaining 3,387 received non-immunologic agents (CHT). Overall, 71 (2%) patients suffered ICM-related ARs. The incidence of ICM-related ARs was higher in Ipi- and Cy-treated patients than in those who received CHT (12%, 5%, and 2%, respectively). Our data show that immunological cancer treatments, particularly Ipi, considerably increase the proportion of patients suffering CECT-related immediate ARs with respect to non-immunologic agents. Although these findings need to be validated in larger prospective studies, they serve as a "wake-up call" for radiologists to closely monitor patients who have previously received cancer immunotherapy with anti-cytotoxic T-lymphocyte antigen-4 antibodies when using ICM in order to reduce the risk of potentially severe immediate ARs.