Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer

Background

To evaluate the metabolic changes on ¹⁸?F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (¹⁸?F-FDG PET-CT) performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiation dose and with the clinical outcome.

Methods

Twenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent ¹⁸?F-FDG PET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PET-CT) of chemo-radiotherapy, and 4?weeks from the end of chemo-radiotherapy (post-RT PET-CT). The parameters evaluated were: the maximum standardized uptake value (SUVmax) of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV).

Results

SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4?weeks from the end of treatment (p<0.0000, p<0.0002, respectively). SUVmax of lymph nodes showed a trend towards a reduction during chemo-radiotherapy (p=0.06) and decreased significantly (p=0.0006) at the end of treatment. There was a significant correlation (r=0.53, p=0.001) between SUVmax of the tumor measured at during-RT PET-CT and the total dose of radiotherapy reached at the moment of the scan. Disease progression free survival was significantly (p=0.01) longer in patients with complete metabolic response measured at post-RT PET-CT.

Conclusions

In patients with locally advanced NSCLC, ¹⁸?F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET.     

In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease

IntroductionThe utility of [¹⁸F]FPBM [2-(2′-((dimethylamino)methyl)-4′-(3-[¹⁸F]-fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [¹⁸F]AV-133 [(+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine], a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model.MethodsPositron emission tomography (PET) imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (Rats 1–3) were performed with [¹⁸F]FPBM and [¹⁸F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [¹⁸F]FPBM and the dopamine transporter ligand, [¹²⁵I]IPT [N-(3′-[¹²⁵I]-iodopropen-2′-yl)-2-beta-carbomethoxy-3-beta-(4-chloro phenyl) tropane, for confirmation. Biodistribution of [¹⁸F]FPBM in a separate group of p-chloroamphetamine (PCA) treated rats were also performed.ResultsPET image analysis showed varying levels of SERT binding reduction (Rat 1=-11%, Rat 2=-4%, Rat 3=-43%; n=2) and a clear and definitive loss of VMAT2 binding (Rat 1=-87%, Rat 2=-72%, and Rat 3=-91%; n=1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (p-chloroamphetamine) showed a significant reduction of [¹⁸F]FPBM uptake in the cortex and hypothalamus regions of the brain.ConclusionThe preliminary data suggest that [¹⁸F]FPBM and [¹⁸F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain.     

An improved radiosynthesis of [18F]AV-133: a PET imaging agent for vesicular monoamine transporter 2

IntroductionRecently, a PET tracer, 9-[¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine ([¹⁸F]AV-133), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system has been reported. It is currently under Phase II clinical trials to establish its usefulness in the diagnosis of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. The radiolabeling of [¹⁸F]AV-133, nucleophilic fluorination reaction and potential effects of pseudo-carrier were evaluated by in vivo biodistribution.MethodsThe preparation of [¹⁸F]AV-133 was evaluated under different conditions, specifically by employing different precursors (–OTs or –Br as the leaving group at the 9-propoxy position), reagents (K222/K₂CO₃ vs. tributylammonium bicarbonate) and solvents (acetonitrile vs. DMSO), reaction temperature and reaction time. With optimized conditions from these experiments, radiosynthesis and purification with solid-phase extraction (SPE) of [¹⁸F]AV-133 were performed by an automated nucleophilic [¹⁸F]fluorination module. In vivo biodistribution in mice on [¹⁸F]AV-133 purified by either HPLC (no-carrier-added) or the SPE method (containing a pseudo-carrier) was performed and the results compared.ResultsUnder a mild fluorination condition (heating at 115°C for 5 min in dimethyl sulfoxide), [¹⁸F]AV-133 was obtained in a high yield using either –OTs or –Br as the leaving group. However, the –OTs precursor gave better radiochemical yields (>70%, thin layer chromatography analysis) compared to those of the –Br precursor. The optimized reaction conditions were successfully implemented to an automated nucleophilic fluorination module. Labeling and purification of [¹⁸F]AV133 were readily achieved via this automatic module in good radiochemical yield of 21–41% (n=10) in 40 min. The radiochemical purity was larger than 95%. Biodistribution of SPE-purified product (containing a pseudo-carrier) in mice showed a high striatum/cerebellum ratio (4.18±0.51), which was comparable to that of HPLC-purified [¹⁸F]AV-133 (4.51±0.10).ConclusionsThe formation of [¹⁸F]AV-133 was evaluated under different labeling conditions. These improved labeling conditions and SPE purification were successfully implemented into an automated synthesis module. This offers a short preparation time (about 40 min), simplicity in operation and ready applicability for routine clinical operation.     

What Does Teaching Declaratives Tell Us About the Criteria by Which we Can Judge the Developmental Importance of Treatment Outcomes?

This paper uses examples of treatment research on declaratives to illustrate criteria for determining whether a taught behavior is a "skill", not just a context-bound behavior and whether the taught skill has associations with other theoretically linked skills as one type of validation evidence. The paper uses data from three treatment studies to illustrate the issues and proposed criteria. The paper concludes with a call to consumers and producers of treatment research to use the criteria to judge the developmental importance of treatment outcomes.     

胃癌及其癌前病变组织Yes相关蛋白和Survivin的表达及其意义

目的:检测YAP和Survivin的表达水平,探讨YAP及Survivin表达与胃癌发生的关系和意义。方法:采用PV9000免疫组化方法分别检测98例胃癌及配对正常胃黏膜,58例肠上皮化生,32例不典型增生组织中YAP和Survivin的表达水平。结果:YAP在不典型增生(37.5%)、胃癌组织(48.0%)中的阳性表达率显著高于正常胃黏膜组织(13.3%),P<0.01;Survivin在肠上皮化生(53.4%)、不典型增生(59.4%)及胃癌(65.3%)组织中的阳性表达率显著高于正常胃黏膜组织(11.2%),P<0.01;弥漫型胃癌组(74.6%)Survivin阳性表达率显著高于肠型胃癌组(51.3%),P<0.05。伴淋巴结转移胃癌组Survivin阳性表达率(76.9%)显著高于无淋巴结转移组(41.2%),P<0.01。在98例胃癌组织中YAP与Sur-vivin表达呈正相关,等级相关系数rk=0.246,P<0.01。结论:YAP可能诱导凋亡抑制因子Survivin的表达,Survivin可能通过抑制胃癌中细胞凋亡及调节细胞有丝分裂的发生进而参与胃癌的发生、发展及转移。将两指标联合检测,有助于...     

T regulatory cell markers in oral squamous cell carcinoma: Relationship with survival and tumor aggressiveness

Tumor-infiltrating lymphocytes (TILs) are a heterogeneous cell family which plays an important role in tumor-associated immune response. Of these, T regulatory (Treg) cells have also been shown to inhibit anti-tumor response. We aimed to evaluate the expression of T regulatory cell markers (CD4, CD25, CTLA-4 and FoxP3) in samples of oral cavity squamous cell carcinoma (OCSCC) and lip SCC (LSCC) by immunohistochemistry. The relationship of Treg markers with survival data and the proliferative index were also evaluated. We observed similar numbers of CD4-, CD25- and FoxP3(+) cells in OCSCC and LSCC. On the other hand, numbers of CTLA-4(+) cells were significantly lower in OCSCC than in LSCC. OCSCC samples with high numbers of CD4 exhibited a high proliferative index, while samples with high CTLA-4 counts demonstrated a low tumoral proliferative index. A log-rank test showed that patients with OCSCC that presented high counts of CD4 showed a significantly decreased survival compared with patients with low cell counts. In contrast, high CD25(+) cell counts were associated with increased survival. Our results suggest an association of CD4 with poor prognosis, while CD25 expression is related with favorable prognosis. These findings result from the heterogeneity of TIL subsets that display an antagonistic role in tumor immune cell response.     

Developing a Quality Screening Colonoscopy Referral System in Primary Care Practice: A Report from the National Colorectal Cancer Roundtable

The use of colonoscopy in colorectal cancer (CRC) screening has increased substantially in recent years. Media messages and changes in insurance reimbursement, as well as new screening guidelines from the American Cancer Society and the US Preventive Services Task Force, have contributed to this increase. Primary care providers (PCPs) are frequently responsible for making the recommendation and referral for screening. The process of successfully referring a patient for screening colonoscopy can be cumbersome and requires a coordinated effort between the PCP and the endoscopist. In recognition of the potential complexity of this process, the National Colorectal Cancer Roundtable has issued a report to describe the components of a quality screening colonoscopy referral system in primary care practice. The elements of a quality program include an optimal scheduling and referral system, the appropriate patient preparation information, consistent reporting and follow–up systems, and a detailed approach to dealing with special situations. CA Cancer J Clin 2010. © 2009 American Cancer Society, Inc.