Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial

<p>Abstract</p> <p>Background</p> <p>Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed.</p> <p>Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.</p> <p>Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions.</p> <p>Methods and design</p> <p>In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study.</p> <p>Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied.</p> <p>The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival.</p> <p>Discussion</p> <p>With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01528683">NCT01528683</a></p

Effect of HNTs modification in nanocomposite membrane enhancement for bacterial removal by cross-flow ultrafiltration system

This study investigated the potential of silver lactate (SL)-holloysite nanotube clay (HNTs) nano-filler embedded into the polyvinylidene fluoride (PVDF) polymer matrix as an antibacterial separator. Three different nanocomposite membranes were fabricated via phase inversion technique aimed to enhance the permeation flux and fouling resistance with complete bacterial rejection. HNT has been modified by N-β-(aminoethyl)-É£-aminopropyltrimethoxy silane (AEAPTMS) aiming for immobilization of SL on the surface HNT during dope preparation. Salmonella and Enterobacter aerogenes (E. aerogenes) were considered as two types of bacteria to be removed from contaminated water in this experimental work. Nanocomposite membranes were characterized and analyzed by thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR), field emission scanning electron microscopy (FESEM) combined with energy dispersive X-ray (EDX), X-ray photoelectron spectroscope (XPS), atomic force microscopy (AFM), contact angle, molecular weight cut-off (MWCO) and tensile strength. Potential silver ion loss was assessed by measuring the silver content in the coagulation bath and in the UF permeate using inductive-coupled plasma mass spectrometer (ICP-MS). Moreover, antibacterial effect of the membrane was examined in terms of removal of microorganisms by filtration, Log Reduction Value (LRV) and thickness of inhibition zone. From the experimental results, the prepared nanocomposite membranes have shown more than 99% bacterial rejection, LRV of more than 3 and broad inhibition zones in the agar plate. In particular, the nanocomposite membrane consisting M-HNTs/SL/PVDF showed significant improvement in permeation flux and flux declination among all the tested membranes. It was also found that modification of HNTs resulted in reduction of silver leaching by uniform distributing of SL, which contributed to significant inhibition for both types of growth bacteria within 24 h of incubation