"Mid-P strategy" versus "internal target volume strategy in locally advanced non small cell lung cancer: Clinical results from the randomized non-comparative phase II study Mid-P.

BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) reported poor 5-year survival rates with frequent local or regional recurrences. Personalized RT may contribute to improve control and clinical outcome. We investigated efficacy and tolerance of "Mid-position" (Mid-P) strategy versus the conventional Internal Target Volume (ITV) strategy in LA-NSCLC patients treated by definitive conformal radiotherapy. METHODS: This prospective non-comparative randomized monocentric phase II trial included adult patients with non-resected, non-metastatic, non-previously irradiated proven LA-NSCLC treated with definitive normo-fractionated conformal radiotherapy (+/- chemotherapy). Allocated patients (randomisation 2:1) were treated using Mid-P or ITV strategy. A Fleming single-stage design (1-sided α = 0.1, 80 % power, P0 = 30 %, P1 = 50 %) planned enrolment of 36 patients in the Mid-P group. The ITV group ensured the absence of selection bias. The primary outcome was 1-year progression-free- survival (1y-PFS) rate. RESULTS: Among 54 eligible patients included from September 2012 to May 2018, 51 patients were analyzed (Mid-P: N = 34; ITV: 17). The 1y-PFS was 38 % (1-sided 95 %CI 25 %-not reached) with Mid-P strategy, and 47 % (95 %CI [27 %-not reached[) with ITV. Loco-regional failure as first event mainly occurred within radiation-field regardless the strategy. Acute and middle-term radiation toxicities were observed with both strategies. CONCLUSION: Local control and survival remain poor using the Mid-P strategy in this prospective randomized non-comparative monocentric study investigating Mid-P strategy versus ITV strategy in LA-NSCLC. Since the Mid-P strategy is not integrated into routine software, and perceived as a time-consuming method, Mid-P strategy cannot be recommended in LA-NSCLCC treated by definitive normo-fractionated conformal radiotherapy outside clinical trials.

Colorectal Adenocarcinoma Mimicking Neuroendocrine Neoplasia on 18 F-FDOPA PET/CT.

ABSTRACT: We present a case of a 48-year-old woman who had previously undergone surgical resection for bladder paraganglioma. An 18 F-FDOPA PET/CT scan performed for suspected colorectal paraganglioma showed intense colorectal uptake associated with adenopathy. Histological examination did not support the presence of a neuroendocrine tumor but instead confirmed the presence of moderately differentiated colorectal adenocarcinoma. Colorectal adenocarcinoma belongs to the list of nonneuroendocrine false-positive tumors that can be detected using 18 F-FDOPA. Therefore, a morphological analysis is important. Thus, 18 F-FDOPA may be a marker for the aggressiveness of colorectal adenocarcinoma.

Patterns of locoregional failure in locally advanced non-small cell lung cancer treated with definitive conformal radiotherapy: Results from the Gating 2006 trial.

PURPOSE: To determine the patterns of locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy (RT). PATIENTS AND METHODS: One hundred and fifty-four patients from the Gating 2006 prospective randomized trial were treated with conformal RT with or without respiratory motion management. For patients with a LRF as first event, treatment planning with simulation CT, pre-treatment 18FDG PET-CT and post-treatment images demonstrating recurrence were registered and analyzed. Measurable LRF was contoured (rGTV) and classified as in-field, marginal, or out-of-field. RESULTS: Median follow-up was 27.8 months. Forty-eight patients presented with LRF. One-year and 2-year locoregional disease-free survival rates were 77% (95% CI 70-83) and 72% (95% CI 64-79) respectively. 79% of the patients with LRF as first event relapsed within the RT field (55% isolated), 30% had marginal LRF component. Isolated out-of-field failure occurred in only 3% of all patients. The regions of highest FDG-uptake on pre-treatment PET-CT were located within the recurrence in 91% of patients with in-field LRF. CONCLUSION: In-field failure was the most common pattern of failure. Escalated dose RT with high-dose fractions guided by PET parameters warrants further investigation.

(123)I-BZA2 as a melanin-targeted radiotracer for the identification of melanoma metastases: results and perspectives of a multicenter phase III clinical trial.

UNLABELLED: Our group has developed a new radiopharmaceutical, (123)I - N-(2-diethylaminoethyl)-2-iodobenzamide ((123)I-BZA2), a benzamide derivative able to bind to melanin pigment in melanoma cells. In a prospective and multicentric phase III clinical study, the value of (18)F-FDG PET/CT and (123)I-BZA2 scintigraphy was compared for melanoma staging. METHODS: Patients with a past history of cutaneous or ocular melanoma were included from 8 hospitals. (18)F-FDG imaging was performed according to a standard PET protocol. Whole-body, static planar, and SPECT/CT (if available) images were acquired 4 h after injection of a 2 MBq/kg dose of (123)I-BZA2. (18)F-FDG and (123)I-BZA2 sensitivity and specificity for the diagnosis of melanoma metastasis were calculated and compared on both a lesion basis and a patient basis. True-positive and true-negative lesion status was determined after 6 mo of clinical follow-up or according to lesion biopsies (if available). Melanin content in biopsies was evaluated with the standard Fontana-Masson silver method and was correlated with (123)I-BZA2 uptake. Based on statistical analysis, the number of inclusions was estimated at 186. RESULTS: In all, 87 patients were enrolled from 2008 to 2010. Of these, 45 (52%) had metastases. A total of 338 imaging abnormalities were analyzed; 86 lesions were considered metastases, and 20 of 25 lesion biopsies found melanoma metastases. In a patient-based analysis, the sensitivity of (18)F-FDG for diagnosis of melanoma metastases was higher than that of (123)I-BZA2, at 87% and 39%, respectively (P < 0.05). For specificity, (18)F-FDG and (123)I-BZA2 were not statistically different, at 78% and 94%, respectively. In a lesion-based analysis, the sensitivity of (18)F-FDG was statistically higher than that of (123)I-BZA2 (80% vs. 23%, P < 0.05). The specificity of (18)F-FDG was lower than that of (123)I-BZA2 (54% vs. 86%, P < 0.05). According to biopsy analysis, only 9 of 20 metastatic lesions (45%) were pigmented with high melanin content. (123)I-BZA2 imaging was positive for 6 of 8 melanin-positive lesions, fairly positive for 3 of 10 melanin-negative lesions, and negative for 7 of 10 melanin-negative lesions. The sensitivity and specificity of (123)I-BZA2 for the diagnosis of melanin-positive lesions were 75% and 70%, respectively. Because of a low (123)I-BZA2 sensitivity, this clinical trial was prematurely closed after 87 patients had been included. CONCLUSION: This study confirms the value of (18)F-FDG PET/CT for melanoma staging and strengthens the high accuracy of (123)I-BZA2 for diagnosis of melanin-positive metastatic melanoma. Moreover, benzamide derivatives radiolabeled with therapeutic radionuclide may offer a new strategy for the treatment of metastatic melanoma patients harboring melanin-positive metastases.

Is [(99m)Tc]glucarate uptake mediated by fructose transporter GLUT-5?

PURPOSE: There is growing interest in the ability of [(99m)Tc]Glucarate ([(99m)Tc]GLA) to accumulate in viable tumor cells. Recent vivo studies suggest that [(99m)Tc]Glucarate could be helpful for tumor detection. Fructose transport is thought to be implicated. It is clearly established that facilitated fructose transport in tumor cells is related to the GLUT-5 transporter. This study therefore investigated whether [(99m)Tc]GLA uptake is mediated by GLUT-5 transporter. METHODS: Different tumor cell lines were used. Modulation of GLUT-5 expression was assessed with and without antisense oligonucleotides directed against GLUT-5. GLUT-5 expression was assessed by indirect cell ELISA. To correlate GLUT-5 expression with tracer accumulation, [(99m)Tc]GLA uptake was determined after antisense treatment. A competition with fructose was also monitored. RESULTS: Inhibition of GLUT-5 expression by antisense oligonucleotides directed against GLUT-5 was effective after 24 h. An optimal of 10µM antisense oligonucleotides directed against GLUT-5 produced a 30%-40% decrease in protein expression. Modulation of [(99m)Tc]GLA uptake was monitored either by use of specific antisense oligonucleotides or by competition with fructose. Both of them produced a significant decrease of [(99m)Tc]GLA accumulation in all tested cell lines. CONCLUSION: Our results clearly demonstrate that [(99m)Tc]GLA uptake is related to GLUT-5 transporter expression and transport. In tumor imaging, [(99m)Tc]GLA may be a useful tool for non-invasive detection of malignant tumors expressing high levels of GLUT-5 transporter as, for example, breast cancers.