Reirradiation with concurrent bevacizumab for recurrent high-grade gliomas in adult patients.

PURPOSE: To analyse feasibility, prognostic factors and patterns of recurrence after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas. PATIENTS AND METHODS: Between 2009 and 2015, 35 patients (median 57-year-old; 21 men, 14 women) with WHO grade III (n=11) or grade IV (n=24) gliomas were included in this retrospective and consecutive single-centre study. All patients received bevacizumab (median number of treatments: 12) concomitant with reirradiation (median dose: 45Gy, median number of fractions: 18) for recurrence with median 22 months (range: 5.6-123.7 months) from first irradiation (median dose: 60Gy). RESULTS: The median follow-up was 9.2 months from reirradiation. The median overall survival from reirradiation was 10.5 months (95% confidence interval [95% CI]: 4.9-16.1) and the progression-free survival from reirradiation was 6.7 months (95% CI: 2.9-10.5). The median overall survival from initial diagnosis was 44.6 months (95% CI: 32-57.1). No grade 3 toxicity or above was reported. Prognostic factors significantly correlated with better overall survival in univariate analysis were: age at least 55 (P=0.024), initial surgery (P=0.003), and 2Gy equivalent dose (EQD2) at least 50Gy at reirradiation (P=0.046). Twenty-two patients bevacizumab-naïve at time of reirradiation had a significantly increased overall survival from reirradiation compared to patients treated with reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P<0.001) as well as overall survival from initial diagnosis (58.9 vs. 33.5 months, P=0.006). This outcome was similar in patients with initial glioblastomas (P=0.018) or anaplastic gliomas (P=0.021). There was no correlation between overall survival and gross tumour volume or planning target volume, frontal localization, or number of salvage therapies before reirradiation (P>0.05). CONCLUSIONS: Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows encouraging results in terms of survival and toxicities. Our data suggest that reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least 50Gy.

Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria.

BACKGROUND: Immune checkpoint inhibitors are an important tool in the therapeutic strategy against metastatic non-small cell lung cancer (NSCLC); however, radiological evaluation is challenging due to the emergence of atypical patterns of responses. Several evaluation criteria have been proposed, such as the Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, immune -related RECIST (irRECIST) and iRECIST, but have not been systematically compared in a homogeneous population. PATIENTS AND METHODS: We conducted a monocentric retrospective analysis of consecutive advanced NSCLC patients treated with an anti-programmed cell death-1 or anti-program death-ligand 1. Response patterns and the discordance between RECIST 1.1, irRECIST and iRECIST guidelines were described, and associations of response patterns and clinical outcome were explored. RESULTS: Overall, 160 patients treated between February 2013 and October 2016 were included. Atypical responses were observed in 20 patients (13%), including eight pseudoprogressions (PsPDs) (5%) and 12 dissociated responses (8%). Thirteen of the 20 patients demonstrated clinical benefit. Per the RECIST 1.1, 37 patients (23%) showed an objective response or stable disease, and 123 patients (77%) exhibited progression. Eighty progressive patients were assessable for irRECIST and iRECIST: 15 patients were assessed differently; however, only three (3.8%) mismatches with a theoretical impact on the therapeutic decision were identified. Patients with PsPD or dissociated response had higher overall survival than patients with true progression. CONCLUSION: Atypical responses (PsPD/dissociated response) occurred in 13% of NSCLC patients under immune checkpoint inhibitors. Based on survival analyses, the RECIST 1.1 evaluation underestimated the benefit of immune checkpoint inhibitors in 11% of the progressive patients. Immune-related RECIST and iRECIST identified these unconventional responses, with a 3.8% discrepancy rate.

[Pulmonary tumor thrombotic microangiopathy]. / Microangiopathie thrombotique tumorale pulmonaire.

Pulmonary tumor thrombotic microangiopathy syndrome is a rare clinicopathological entity in which tumor cell micro-emboli in the pulmonary microcirculation induced thrombotic microangiopathy. This can cause respiratory failure, and acute or sub-acute right heart failure. Histological features include micro tumor emboli in the small arteries and arterioles of the lung associated with thrombus formation and fibro-cellular and fibro-muscular intimal proliferation. The diagnosis is however extremely difficult to make before death. Thus, most of the observations reported are based on autopsy data. Very rare diagnostic observations made before death suggest the potential effectiveness of chemotherapy. Many details remain to be elucidated, interdisciplinary research is a priority with close collaboration between pathologists and clinicians to better understand this, often fatal, syndrome. It may be that the use of targeted therapies will improve the very poor prognosis allowing survival of several weeks or months after diagnosis.

Radiological evaluation of response to treatment: application to metastatic renal cancers receiving anti-angiogenic treatment.

Targeted therapies have considerably improved the prognosis of patients with metastatic renal cancer (mRCC) but there are no reliable response assessment criteria reflecting the clinical benefits, because there is no regression in size, or it is delayed. Such criteria would help early identification of non-responders, who would then benefit from a change of treatment, and would avoid their being subjected to unnecessary side effects related to the treatment. We will review the imaging techniques currently available for evaluating tumour response in mRCC patients, including the response evaluation criteria in solid tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size and attenuation criteria (SACT). We will also discuss functional imaging techniques, which are based on the physiological characteristics of the tumours, such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI, DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET) tracers. It is not possible at present to propose a unanimously acknowledged criterion for evaluating tumour response to targeted therapy. However, there is a real need for this according to oncologists and the pharmaceutical industry, and radiologists need to be involved in reflecting on the subject.

Imaging criteria for assessing tumour response: RECIST, mRECIST, Cheson.

Most methods define a limited number of "target" lesions to be measured and other "non-target" lesions to be evaluated qualitatively. RECIST criteria are the most widely used although other criteria have been proposed that are derived from them based on size alone, or size and attenuation. Modified RECIST (mRECIST) criteria only concern hepatocellular carcinoma and only take into account the viable portion (enhanced after injection during the arterial phase). Cheson criteria are more complex as target lesions are defined differently depending on the organ (lymph nodes, liver or spleen, other organs), and involve both CT and PET scans, as well as the clinical examination and bone marrow biopsy.

Whole body MRI in paediatric oncology.

Whole body MRI provides excellent contrast resolution imaging and is an interesting alternative to nuclear medicine examinations in paediatric oncology because it does not involve exposure to radiation. This technique, now feasible in clinical practice, helps to evaluate metastatic spread and response to treatment, which are of great prognostic interest. Numerous studies have demonstrated the non-inferiority of this technique when compared to nuclear medicine examinations. However, there is still a need to standardize indications in each type of cancer and at every stage of it. This article first discusses the technical principles of whole body MRI, then reviews current clinical applications for the modality in children, and finally, discusses future useful developments for paediatric oncology.

Percutaneous image-guided cryoablation in inoperable extra-abdominal desmoid tumors: a study of tolerability and efficacy.

OBJECTIVE: To determine the tolerability, effectiveness and outcomes of percutaneous image-guided cryoablation on inoperable extra-abdominal desmoid tumors. METHODS: Between 2011 and 2012, 13 patients (mean age 39.3 years, range 15-74) with inoperable extra-abdominal desmoid tumors were consecutively treated with cryoablation (17 tumors treated in 17 procedures), including two patients with Gardner syndrome and nine recurrences after surgery. Disease-free survival (DFS) and local control based on RECIST criteria were calculated on prospective clinical and imaging follow-up until 2013. RESULTS: Cryoablation was performed under ultrasound (n = 8), computed tomography (n = 1), or combined (n = 8) guidance, and under general (n = 15) or local (n = 2) anesthesia. A major complication was observed in one session (5.8%). Mean follow-up was 11.3 months (6-27 months). Among all the patients treated, eight patients (47%) presented residual tumors on the first magnetic resonance follow-up, which were asymptomatic. The DFS rate was stable at 82.3% (95% confidence interval 0.55-0.94) at 6, 12, and 24 months. The local tumor progression rate was 0% at 6, 12, and 24 months. Two patients (12%) presented an in situ recurrence. CONCLUSIONS: Despite high rates of partial ablation, percutaneous image-guided cryoablation appears to be safe and effective for local control for patients with inoperable extra-abdominal desmoid tumors.

Malignant head/neck paragangliomas. Comparative study.

BACKGROUND: The objective of this study was to report 11 cases of malignant head and neck paraganglioma and to compare their epidemiological, clinical, and genetic characteristics, their natural history and their treatment with those of a series of 131 benign paragangliomas. PATIENTS AND METHODS: Retrospective analysis of 142 patients with head and neck paraganglioma managed between 2001 and 2008. Age at the time of diagnosis, gender, primary tumour site, presence of other non-head/neck paragangliomas and/or metastases diagnosed by imaging (CT, MRI, Octreoscan or (18)F-FDG PET), histology, urinary catecholamine and metanephrine levels, family history, and genetic test results were recorded. RESULTS: This series comprised 131 benign head and neck paragangliomas, mostly observed in women with a mean age at diagnosis of 45 years and a predominance of tympanojugular sites (followed by carotid and vagal sites) with 5% of secreting tumours and 20% of multifocal tumours. Eleven patients (7.7%) with a 1:1 sex ratio presented criteria of malignancy. These patients, with a lower mean age (38 years), predominantly presented carotid lesions with a higher rate of secreting and multifocal tumours, 27% and 46% respectively. The main sites of metastases were bone and lymph nodes. No tympanic paragangliomas were observed. CONCLUSIONS: Malignant paragangliomas are mainly observed in young patients with multifocal tumours, particularly carotid tumours, and are predominantly related to subunit SDH-B mutation. The work-up in these high-risk patients must include whole body scintigraphy and spine MRI. Malignancy is not necessarily associated with a poor short-term prognosis due to the slow course of the disease.

Breast elastography: the technical process and its applications.

Breast elastography is being increasingly used to better characterize breast lesions. Published studies have shown that it improved specificity of B mode ultrasound. Two elastography modes are available: free-hand elastography and shear wave elastography. Free-hand elastography is obtained by a mechanic wave induced by the ultrasound probe, deforming the target, either by small movements induced by breathe. An elastogram is obtained and displayed either as a colour map or a size ratio or elasticity ratio measurement. The second mode is shear wave elastography; two methods are available: Shear Wave Elastography (SWE) and ARFI mode (Acoustic Radiation Force Impulse). Shear wave elastography is less operator-dependent than free-hand elastography mode and provides a quantitative approach. A value of over 80kPa (SWE) or velocity results of over 2m/s (ARFI) are considered as suspicious. False negatives may occur in soft breast cancers (mucinous carcinoma, carcinoma with an inflammatory stroma, etc.) and false positives may be seen with poorly deformable benign lesions such as old fibrous adenomas. In practical use, elastography is a useful complementary tool for undetermined breast lesions categorized as BI-RADS 4a or BI-RADS 3, or for cystic lesions but cannot avoid fine needle aspiration or core biopsy if ultrasound features are clearly suspicious.

Radiologically guided percutaneous cryotherapy for soft tissue tumours: A promising treatment.

Studies of percutaneous cryotherapy in the treatment of benign or malignant soft tissue tumours are rare and mainly involve small populations. Nevertheless, results show cryotherapy's potential in terms of local control of tumours, analgesic efficacy, reduced intra- and postoperative complications, and reduction in the length of convalescence after the procedure. The objective of this update is to set out the short-term prospects for this technique in the treatment of soft tissue tumours, so that it may be more widely offered in these indications.

Verrucous carcinoma of the skin: case report with literature review.

We present a case of verrucous carcinoma of the axilla with multiple recurrences and we review the literature with regard to the optimal therapeutic approach for this rare entity.

Gastrointestinal tract metastasis as first presentation of breast cancer.

Gastrointestinal metastases of breast cancer are a rare occurrence. It is even rarer to be the first manifestation of an unknown breast cancer. We present 2 cases of metastatic breast cancer of the lobular type to the stomach and large bowel in 2 women, initially considered as primary disease. The establishment of diagnosis required experienced histopathologic and immunohistochemical examination. The management follows the principles of the primary disease. Surgery is spared for complications. Mean survival is one year. Prognosis is better for patients with positive hormonal receptors.

Malignant paraganglioma of the abdomen.

We present a case of non-functioning malignant paraganglioma of the abdomen with cervical lymph node metastases. At laparotomy the tumor was considered unresectable. The patient received palliative radiation therapy and died 3 months later from disseminated disease. We discuss the diagnostic approach and the therapeutic options.