Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT).

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.

Intratumoral immunotherapy: using the tumor as the remedy.

Immune checkpoint-targeted monoclonal antibodies directed at Programmed Death Receptor 1 (PD-1), Programmed Death Ligand 1 (PD-L1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4) are currently revolutionizing the prognosis of many cancers. By blocking co-inhibitory receptors expressed by antitumor T cells, these antibodies can break the immune tolerance against tumor cells and allow the generation of durable cancer immunity. Benefits in overall survival over conventional therapies have been demonstrated for patients treated with these immunotherapies, leading to multiple approvals of such therapies by regulatory authorities. However, only a minority of patients develop an objective tumor response with long-term survival benefits. Moreover, the systemic delivery of immunotherapies can be responsible for severe auto-immune toxicities. This risk increases dramatically with anti-PD(L)1 and anti-CTLA-4 combinations and currently hampers the development of triple combination immunotherapies. In addition, the price of these novel treatments is probably too high to be reimbursed by health insurances for all the potential indications where immunotherapy has shown activity (i.e. in more than 30 different cancer types). Intratumoral immunotherapy is a therapeutic strategy which aims to use the tumor as its own vaccine. Upon direct injections into the tumor, a high concentration of immunostimulatory products can be achieved in situ, while using small amounts of drugs. Local delivery of immunotherapies allows multiple combination therapies, while preventing significant systemic exposure and off-target toxicities. Despite being uncertain of the dominant epitopes of a given cancer, one can therefore trigger an immune response against the relevant neo-antigens or tumor-associated antigens without the need for their characterization. Such immune stimulation can induce a strong priming of the cancer immunity locally while generating systemic (abscopal) tumor responses, thanks to the circulation of properly activated antitumor immune cells. While addressing many of the current limitations of cancer immunotherapy development, intratumoral immunotherapy also offers a unique opportunity to better understand the dynamics of cancer immunity by allowing sequential and multifocal biopsies at every tumor injection.

Lung ablation: Best practice/results/response assessment/role alongside other ablative therapies.

Today, in addition to surgery, other local therapies are available for patients with small-size non-small-cell lung cancer (NSCLC) and oligometastatic disease from various cancers. Local therapies include stereotactic ablation radiotherapy (SABR) and thermal ablative therapies through percutaneously inserted applicators. Although radiofrequency ablation (RFA) has been explored in series with several hundreds of patients with pulmonary tumours, investigation of the potential of other ablation technologies including microwave ablation, cryoablation, and irreversible electroporation is ongoing. There are no randomised studies available to compare surgery, SABR, and thermal ablation. In small-size lung metastases, RFA seems to produce results very close to surgical series with >90% local control and 5-year overall survival of 50%. In primary lung cancer, the technique is reserved for non-surgical candidates. In future, the low invasiveness of thermal ablative therapies will allow for a combination of ablation and systemic therapies in order to improve the outcomes of ablation alone. Another major advantage of thermal ablation is the possibility to treat several metastases in close proximity to one another and retreatment in the same location in case of failure, which is not possible with SABR.

Conversion to resection of liver metastases from colorectal cancer with hepatic artery infusion of combined chemotherapy and systemic cetuximab in multicenter trial OPTILIV.

BACKGROUND: Systemic chemotherapy typically converts previously unresectable liver metastases (LM) from colorectal cancer to curative intent resection in ∼15% of patients. This European multicenter phase II trial tested whether hepatic artery infusion (HAI) with triplet chemotherapy and systemic cetuximab could increase this rate to 30% in previously treated patients. PATIENTS AND METHODS: Participants had unresectable LM from wt KRAS colorectal cancer. Main non-inclusion criteria were advanced extra hepatic disease, prior HAI and grade 3 neuropathy. Irinotecan (180 mg/m(2)), oxaliplatin (85 mg/m(2)) and 5-fluorouracil (2800 mg/m(2)) were delivered via an implanted HAI access port and combined with i.v. cetuximab (500 mg/m(2)) every 14 days. Multidisciplinary decisions to resect LM were taken after every three courses. The rate of macroscopic complete resections (R0 + R1) of LM, progression-free survival (PFS) and overall survival (OS) were computed according to intent to treat. RESULTS: The patient population consisted of 42 men and 22 women, aged 33-76 years, with a median of 10 LM involving a median of six segments. Up to 3 extrahepatic lesions of <1 cm were found in 41% of the patients. A median of six courses was delivered. The primary end point was met, with R0-R1 hepatectomy for 19 of the 64 previously treated patients, 29.7% (95% confidence interval 18.5-40.9). Grade 3-4 neutropenia (42.6%), abdominal pain (26.2%), fatigue (18%) and diarrhea (16.4%) were frequent. Objective response rate was 40.6% (28.6-52.3). Median PFS and OS reached 9.3 (7.8-10.9) and 25.5 months (18.8-32.1) respectively. Those with R0-R1 hepatectomy had a median OS of 35.2 months (32.6-37.8), with 37.4% (23.6-51.2) alive at 4 years. CONCLUSION: The coordination of liver-specific intensive chemotherapy and surgery had a high curative intent potential that deserves upfront randomized testing. PROTOCOL NUMBERS: EUDRACT 2007-004632-24, NCT00852228.

Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases.

BACKGROUND: Minimal invasive methods are needed as an alternative to surgery for treatment of lung metastases. PATIENTS AND METHODS: The prospective database of two cancer centers including all consecutive patients treated with radiofrequency ablation (RFA) for lung metastasis over 8 years was reviewed. RFA was carried out under general anesthesia, with computed tomography guidance using a 15-gauge multitined expandable electrodes RF needle. RESULTS: Five hundred sixty-six patients including 290 men (51%), 62.7 ± 13.2 years old with primary tumor to the colon (34%), rectum (18%), kidney (12%), soft tissue (9%) and miscellaneous (27%) received 642 RFA for 1037 lung metastases. Fifty-three percent of patients had 1 metastasis, 25% had 2, 14% had 3, 5% had 4 and 4% had 5-8. Metastases were unilateral (75%), or bilateral (25%). The median diameter [extremes] of metastases was 15 mm (4-70). Twenty-two percent of patients had extrapulmonary disease amenable to local therapy including 49 liver, 16 bone and 60 miscellaneous metastases. Median follow-up was 35.5 months. Median overall survival (OS) was 62 months. Four-year local efficacy was 89%. Four-year lung disease control rate was 44.1%, with patient retreated safely up to four times. Primary origin, disease-free interval, size and number of metastases were associated with OS in multivariate analysis. Progression at RFA site was associated with poor OS [P = 0.011, hazard ratio (HR): 1.69 (95% confidence interval 1.13-2.54)]. In the 293 colorectal cancer metastases, size >2 cm (HR = 2.10, P = 0.0027) and a number of metastases ≥3 (HR = 1.86, P = 0.011) remained significantly associated with OS. A prognostic score made of three groups based on the four above-mentioned prognostic factors demonstrated 3-year OS rates of respectively 82.2%, 69.5% and 53.6% (log-rank test, P ≤ 0.0001) among the three groups in the overall population, and of 81.3%, 72.8% and 57.9% (log-rank test, P = 0.005) in the colorectal cancer patients. CONCLUSION: Radiofrequency is an option for treatment of small size lung metastases, namely the ones below 2-3 cm.

Thermal ablation techniques: a curative treatment of bone metastases in selected patients?

INTRODUCTION: Thermal ablation techniques (radiofrequency-ablation/cryotherapy) can be indicated with a curative intent. The success rate and prognostic factors for complete treatment were analysed. MATERIAL/METHODS: The medical records of all patients who had undergone curatively intended thermal ablation of bone metastases between September 2001 and February 2012 were retrospectively analysed. The goal was to achieve complete treatment of all bone metastases in patients with oligometastatic disease (group 1) or only of bone metastases that could potentially lead to skeletal-related events in patients with a long life expectancy (group 2). We report the rate of complete treatment according to patient characteristics, primary tumour site, bone metastasis characteristics, radiofrequency ablation/cryotherapy and the treatment group (group 1/group 2). RESULTS: Eighty-nine consecutive patients had undergone curatively intended thermal ablation of 122 bone metastases. The median follow-up was 22.8 months [IQR = 12.2-44.4]. In the intent-to-treat analysis, the 1-year complete treatment rate was 67% (95%CI: 50%-76%). In the multivariate analysis the favourable prognostic factors for complete local treatment were oligometastatic status (p = 0.02), metachronous (p = 0.004) and small-sized (p = 0.001) bone metastases, without cortical bone erosion (p = 0.01) or neurological structures in the vicinity (p = 0.002). CONCLUSION: Thermal ablation should be included in the therapeutic arsenal for the cure of bone metastases. KEY POINTS: • Thermal ablation techniques are currently performed to palliate pain caused by bone metastases. • In selected patients, thermal ablation can also be indicated with a curative intent. • Oligometastatic and/or metachronous diseases are good prognostic factors for local success. • Small-size (<2 cm) bone metastases and no cortical erosion are good prognostic factors.

Developing a Clinical Service in Interventional Radiology: Results from the 2024 CIRSE Clinical Practice Survey.

PURPOSE: Engaging in clinical service development is a prerequisite for Interventional Radiology (IR) to prosper as a full clinical discipline. The CIRSE Clinical Services in IR Task Force conducted a survey of CIRSE members worldwide to assess the current status of their clinical practice and to identify areas of practice requiring further support. MATERIALS AND METHODS: An online questionnaire with 63 structured items was sent to 7,501 CIRSE members in November 2023. The survey was closed in January 2024 and a statistical data analysis was performed. RESULTS: A total of 520 complete responses were collected. 49.6% of respondents have an IR outpatient clinic, 34.5% have a dedicated IR day-case ward and 19.8% have dedicated inpatient beds. While 62% of respondents treat patients as the primary consultant responsible for their patients' care, 40.3% of respondents currently without their own beds have admitting rights to the hospital. Clinical practice activities are itemised in the work schedule of 41.3% of respondents and 45% routinely perform ward rounds. A total of 40% feel very positive with their personal clinical practice competency. CONCLUSION: With half of responding IRs having primary patient access and clinical services in place, the results are encouraging; however further engagement by those who are not yet involved is required. The authors advocate a step-wise approach towards clinical services starting with ward rounds, and subsequently taking increasing responsibility for each step in the IR patient pathway.

A phase I, dose-escalation study of the Eg5-inhibitor EMD 534085 in patients with advanced solid tumors or lymphoma.

BACKGROUND: The kinesin spindle protein Eg5 is involved in mitosis, and its inhibition promotes mitotic arrest. EMD 534085, a potent, reversible Eg5 inhibitor, demonstrated significant preclinical antitumor activity. METHODS: This first-in-man, single-center, open-label, phase I dose-escalation study (3 + 3 design) investigated EMD 534085 safety, pharmacokinetics and antitumor activity in refractory solid tumors, Hodgkin's lymphoma, or non-Hodgkin's lymphoma. EMD 534085 (starting dose 2 mg/m²/day) was administered intravenously every 3 weeks. Doses were escalated in 100% steps in successive cohorts of 3 patients until grade 2 toxicity occurred, followed by 50% until the first dose-limiting toxicity (DLT) arose. If <2 of 6 patients experienced a DLT, doses were further increased by 25%. Dose-escalation was stopped if a DLT occurred in ≥2 of 6 patients. RESULTS: Forty-four patients received EMD 534085. Median treatment duration was 43 days (range, 21-337). Thirty-eight patients (86%) received ≥2 cycles. DLTs were grade 4 neutropenia (1 patient each at 108 and 135 mg/m²/day), and grade 3 acute coronary syndrome with troponin I elevation (1 patient at 135 mg/m²/day). The maximum tolerated dose (MTD) was 108 mg/m²/day. The most common treatment-related adverse events were asthenia (50%) and neutropenia (32%). EMD 534085 appeared to have linear pharmacokinetics. Increase in phospho-histone H3 positive cells in paired pre- and on-treatment biopsies showed evidence of target modulation. No complete or partial responses were observed. Best response was stable disease in 23 patients (52%). CONCLUSIONS: EMD 534085 appeared to be well tolerated; MTD was 108 mg/m²/day. Preliminary antitumor results suggested limited activity in monotherapy.

The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

Sequential research-related biopsies in phase I trials: acceptance, feasibility and safety.

BACKGROUND: Sequential tumour biopsies are of potential interest for the rational development of molecular targeted therapies. PATIENTS AND METHODS: From June 2004 to July 2009, 186 patients participated in 14 phase I clinical trials in which sequential tumour biopsies (13 trials) and/or sequential normal skin biopsies (6 trials) were optional. All patients had to sign an independent informed consent for the biopsies. RESULTS: Tumour biopsies were proposed to 155 patients and 130 (84%) signed the consent while normal skin biopsies were proposed to 70 patients and 57 (81%) signed the consent. Tumour biopsies could not be carried out in 41 (31%) of the 130 consenting patients. Tumour biopsies were collected at baseline in 33 patients, at baseline and under treatment in 56 patients. Tumour biopsies were obtained using an 18-gauge needle, under ultrasound or computed tomography guidance. Only nine minor complications were recorded. Most tumour biopsy samples collected were intended for ancillary molecular studies including protein or gene expression analysis, comparative genomic hybridization array or DNA sequencing. According to the results available, 70% of the biopsy samples met the quality criteria of each study and were suitable for ancillary studies. CONCLUSIONS: In our experience, the majority of the patients accepted skin biopsies as well as tumour biopsies. Sequential tumour and skin biopsies are feasible and safe during early-phase clinical trials, even when patients are exposed to anti-angiogenic agents. The real scientific value of such biopsies for dose selection in phase I trials has yet to be established.

Validation of a modified algorithm for the identification of yeast isolates using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS).

Optimising antifungal treatment requires the fast and species-specific identification of yeast isolates. We evaluated a modified protocol for the rapid identification of clinical yeast isolates using matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) technology. First, we evaluated a simplified extraction procedure using 54 clinical yeast isolates. Second, we validated a new protocol with this simplified extraction procedure and lower identification threshold by analysing 167 isolates with either MALDI-TOF or conventional identification techniques. MALDI-TOF analysis with both the standard and short extraction procedure yielded identical identification results, although the log-scores were lower with the latter. With the modified protocol, 163/167 (97.6%) isolates showed a correct identification as compared to conventional identification techniques. A total of 135 out of the 163 (82.8%) correct identifications showed log-scores above 1.7, which we considered as the minimum log-score for secure species identification. The rapid identification of clinical yeast isolates is crucial in patient management. The MALDI-TOF technique using a short extraction procedure can be an alternative for the labourious standard procedure, although the log-scores will be lower. The identification of clinical yeast isolates with the modified protocol is a practical and accurate alternative for conventional identification techniques. If the isolate shows a log-score below 1.7, the standard extraction procedure should be used.

Postgraduate oncology educational shifts during the COVID-19 pandemic: results of faculty and medical student surveys.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted clinical practice, research and teaching. During peaks, virtual courses were implemented but these changes are poorly described, especially for oncology postgraduate students and faculty teachers. PATIENTS AND METHODS: We administered two surveys from June 2021 to October 2021 to students and faculty teachers (250 and 80 responses, respectively) who registered at Gustave Roussy School of Cancer Sciences (Université Paris-Saclay) during 3 consecutive university years (October 2018 to October 2021), where a major shift to e-learning was associated with COVID-19 pandemic. RESULTS: Most students were female (53%), attending physicians (50%), aged 30-39 years (54%) and 2020-2021 (66.4%) was the main year of training. Most faculty teachers were male (58%), aged 40-50 years (44%) and had participated in training for at least 3 years (83%). More than half of the students received 100% virtual training [55% versus 45% face-to-face/mixed teaching modalities; online (84%) versus remote teaching (16%)]. Only 34% of students declared >80% 'active listening' and only 16% of teachers considered e-learning to be more suitable (compared with face-to-face) for postgraduate education. Virtual teaching decreased student-teacher interactions as compared with mixed/face-to-face (lessons were sufficiently interactive for 54% students if virtual only teaching versus for 71% if other teaching modalities; P = 0.009). Teachers stated that virtual learning did not lead to any improvements in terms of attendance (68%), interaction (74%) and quality of teaching (68%). However, most faculty (76%) acknowledged that partial e-learning training should be maintained outside the pandemic, if it represents ≤50% of the whole teaching (teachers: 79% versus student: 66%; P = 0.04). CONCLUSIONS: COVID-19 accelerated the transition toward novel practices. Students and faculty teachers agreed on the need for future mixed (≤50% e-learning) teaching modalities. Adequate formation and the use of codified best newer virtual practices are required.

Percutaneous Transpedicular Fixation by PEEK Polymer Implants Combined with Cementoplasty for Vertebral Compression Fractures: A Pilot Study.

PURPOSE: To evaluate the feasibility and safety of percutaneous transpedicular fixation by PEEK polymer implants and cementoplasty for vertebral compression fracture (VCF). MATERIALS AND METHODS: From February 2019 to December 2019, 6 consecutive patients (3 men and 3 women; mean age 55 ± 8 years; range 40-64 years) who had percutaneous transpedicular fixation with cementoplasty for the treatment of VCF (5 tumor lesions, 1 traumatic) were included. The procedure duration, length of hospital stay, and complications were reported. Visual analog scale (VAS) and the Oswestry disability index (ODI) for pain and disability were assessed before and 2 months after the procedure. RESULTS: The mean procedure duration was 74 ± 47 min (range 20-140 min). The median length of hospital stay was 3 days (range 2-63) after the procedure. Only minor adverse events were reported (4 asymptomatic cement leakages) but no severe complications. No cases of procedural site fracture during follow-up were noted (median 198 days; range 78-238 days). The mean VAS score decreased from 6.2 ± 1.8 mm (median 6 mm; range 4-9 mm) before the procedure to 1.7 ± 2.1 mm (median 1; range 0-5 mm) after the procedure. The ODI decreased from 36 ± 14% (range 18-54%) before the procedure to 23 ± 10% (range 11-30%) at 2-months follow-up. CONCLUSIONS: Percutaneous transpedicular fixation of VCF by PEEK implants with cementoplasty appears feasible and safe.

Radiofrequency ablation versus surgical resection for the treatment of oligometastatic lung disease.

PURPOSE: The purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease. MATERIALS AND METHODS: This retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and pulmonary or local tumor progression rates. RESULTS: Among 204 patients identified, 78 patients (42 men, 36 women; mean age, 53.3±14.9 [SD]; age range: 15-81 years) were treated surgically, while 126 patients (59 men, 67 women; mean age, 62.2±10.8 [SD]; age range: 33-80 years) were treated by RFA. In the RFA cohort, patients were significantly older (P<0.0001), with more extra-thoracic localisation (P=0.015) and bilateral tumour burden (P=0.0014). In comparison between surgery and RFA cohorts, respectively, the 1- and 3-year OS were 94.8 and 67.2% vs. 94 and 72.1% (P=0.46), the 1- and 3-year PFS were 49.4% and 26.1% vs. 38.9% and 14.8% (P=0.12), the pulmonary progression rates were 39.1% and 56% vs. 41.2% and 65.3% (P>0.99), and the local tumour progression rates were 5.4% and 10.6% vs. 4.8% and 18.6% (P=0.07). Tumour size>2cm was associated with a significantly higher local tumor progression in the RFA group (P=0.010). Hospitalisation stay was significantly shorter in the RFA group (median of 3 days; IQR=2 days; range: 2-12 days) than in the surgery group (median of 9 days; IQR=2 days; range: 6-21 days) (P<0.01). CONCLUSION: RFA should be considered a minimally-invasive alternative with similar OS and PFS to surgery in the treatment of solitary or multiple lung metastases measuring less than 4cm in diameter without associated pleural involvement or thoracic lymphadenopathy.

Endocrine pancreatic tumours: which are the most useful MRI sequences?

OBJECTIVES: To determine magnetic resonance imaging (MRI) signal and enhancement characteristics of endocrine pancreatic tumours (ETPs) and which MR sequences show them most consistently. METHODS: Fifty-five consecutive patients with 68 ETPs underwent 1.5-T abdominal MRI comprising T2-weighted, unenhanced T1-weighted and dynamic T1-weighted after injection of gadopentetate dimeglumine sequences. Twenty-one patients underwent diffusion-weighted imaging (DWI). Two radiologists identified the number, location, size, signal and enhancement patterns of ETPs, and determined a confidence scale indicating the presence of tumours on DWI. The results were compared with echo-endoscopy (endoscopic ultrasound) findings. RESULTS: The detection sensitivity was 95%, similar to that of echo-endoscopy. T2-weighted and T1-weighted sequences at the arterial phase had the highest contrast-to-noise ratio (CNR) median value. On DWI, the mean sensitivity was 65%. The mean apparent diffusion coefficient (ADC) value of ETP was significantly lower than in the normal parenchyma. CONCLUSION: In suspected ETP, MRI is a sensitive method, similar to echo-endoscopy and could be recommended as the first imaging technique. T2-weighted sequences and T1-weighted sequences in the arterial phase are the optimal pulse sequences. The quantitative assessment of ADC values is a promising tool for the characterisation of pancreatic lesions.

Interventional oncology at the time of COVID-19 pandemic: Problems and solutions.

The COVID-19 pandemic has deeply impacted the activity of interventional oncology in hospitals and cancer centers. In this review based on official recommendations of different international societies, but also on local solutions found in different expert large-volume centers, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology. A literature review of potential solutions in a context of scarce anesthesiologic resources, limited staff and limited access to hospital beds are proposed and discussed based on the literature data.

Otitis media microbes: culture, PCR, and confocal laser scanning microscopy.

OBJECTIVES: To assess the presence of middle ear pathogens in nasopharynx (NP), middle ear fluid (MEF), and middle ear mucosal swabs (MES) of 14 patients undergoing middle ear surgery. METHODOLOGY: Bacteria were assessed by culture and species specific PCR. Biofilm was investigated by confocal laser scanning microscopy (CLSM) of middle ear biopsies (MEBs). RESULTS: Bacteria were absent in CLSM of MEBs in three of the four closed and healthy middle ears. Bacteria occurred in the ear with a foreign body (middle ear prosthesis), which showed localized living and dead bacteria, indicating biofilm. Bacterial growth was present in ten patient ears, but biofilm occurred in only one patient. CLSM indicated biofilm in the middle ear of two patients for whom PCR detected Haemophilus influenzae in the MEF. The three classical pathogens could frequently be found in the nasopharynx, by culture and PCR, but not from the middle ear. Alloiococcus otitidis was detected in the MEF of all five patients with open inflamed ears, though virtually absent from the nasopharynx. Pseudomonas aeruginosa was present in seven. It was the only pathogen found on several occasions in all three locations in one patient. CONCLUSIONS: This study confirms the association of H. influenzae with middle ear biofilm, and indicates a potential role of P. aeruginosa in middle ear inflammation and biofilm formation. Biofilm does not seem to cause inflammation. It is unclear whether the predominance of A. otitidis in chronically inflamed open middle ears indicates a pathogenic or contaminant role for this organism.

Thermal-ablation of vertebral metastases prevents adverse events in patients with differentiated thyroid carcinoma.

PURPOSE: To evaluate a strategy that used thermal-ablation of vertebral metastases (VM) to prevent vertebral related events (VRE) in patients with differentiated thyroid cancer (DTC). METHODS: This single center study retrospectively reviewed records and post-operative imaging of all DTC patients treated with thermal-ablation for asymptomatic VMs. Rate of local tumor control at first post-operative imaging, 12 and 24 months after thermal-ablation and rate of VREs at 12 and 24 months among the treated VMs were reported. New VMs that occurred during the follow-up and were not considered for additional thermal-ablation were moniroted and VREs were reported. RESULTS: Thermal-ablation was used to achieve local control of 41 VMs in 28 patients. Median post-treatment follow-up was 22 months [range: 12-80] and the mean delay for first post-operative imaging was 2 months [range: 0.6-7.5]. Local control at first post-operative imaging, 12 and 24 months was achieved in 87.8%, 82.9% and 75.6%, respectively. Among the treated VMs the rates of VRE was 7.3% at 2 years, significantly lower if local control was achieved at first post-operative imaging than if it was not (0% vs 30%, p = 0.011, OR = 0.184 [95%CI = 0.094-0.360]). After thermal-ablation procedures, 19 news VMs occurred in 11 patients (39.2%) with a median interval of 8 months [range 1-26] and remained untreated. Among these untreated VMs, the rate of VREs at 2 years was significantly higher compared to the treated VMs: (36.8% vs. 7.3%, p = 0.008, OR = 0.135, [95%CI = 0.030-0.607]). CONCLUSION: local tumor control of VMs using thermal-ablation decreases the risk of VREs in DTC patients.