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Objectives:We assessed the impact of three-dimensional (3D) conformal planning vs conventional planning of preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) on small bowel and bladder sparing and in optimising coverage of tumour target volume. Methods: Conformal and conventional plans were created for 50 consecutive patients. The conformal plan delineated a gross tumour volume (GTV), a clinical target volume (CTV) 1 to cover potential subclinical disease spread, a CTV2 to outline the mesorectum and lymph node areas at risk, and a planning target volume (PTV) to cover set-up error and organ movement. The conventional plan was created using digitally reconstructed radiographs (DRRs). Patients were treated with a dose of 45 Gy in 25 fractions with concurrent chemotherapy over 5 weeks. Dose-volume histograms (DVHs) were created and compared for GTV, PTV, small bowel and bladder. The GTV was covered by the conventional plan in all patients. Results: Significant differences were shown for median PTV coverage with conformal planning compared with conventional planning: 99.2% vs 94.2% (range 95.9-100% vs 75.5-100%); p,0.05. The median volume of irradiated small bowel was significantly lower for CT plans at all DVH levels. Median bladder doses did not differ significantly. Conclusion: 3D conformal CT planning is superior to conventional planning in terms of coverage of the tumour volume. It significantly reduces the volume of small bowel irradiated with no decrease in the rate of R0 resection compared with published data, and at the present time should be considered as the standard of care for rectal cancer planning. Chemoradiotherapy (CRT) followed by total mesorectal excision is the standard for care when MRI staging demonstrates threatened surgical margins in locally advanced rectal cancer (LARC) [1,2]. Radiotherapy planning for rectal cancer uses conventional orthogonal simulation with standardised radiation fields based on patterns of loco-regional relapse in relation to pelvic bony anatomy [3]. Three-field conventional orthogonal planning is considered an acceptable technique for planning preoperative CRT and major trials evaluating long-course chemoradiation for rectal cancer have permitted the use of conventional planning within their protocols [4,5]. In recent years, the treatment of rectal cancer has improved through advances in the planning and delivery of radiotherapy as well as improved preoperative imaging with MRI, the development of surgical techniques using total mesorectal excision (TME) and more accurate histopathological reporting [6]. Radiotherapy planning must ensure all clinically and radiologically identifiable disease is encompassed while still minimising the dose to the surrounding organs at risk, particularly the small bowel and bladder. Potential areas of microscopic spread and the appropriate pelvic lymph nodes should also be treated.Preoperative MRI has improved the knowledge of pelvic anatomy and identification of pelvic lymph nodes at risk according to tumour l...

Purpose Modulated electro-hyperthermia (mEHT) stands to be a significant technological advancement in the hyperthermia field, utilizing autofocusing electromagnetic power on the cell membrane to create massive apoptosis. Since mEHT possesses the unique ability to excite cell membranes, we hypothesized that mEHT could enhance the uptake of liposomal drugs by enhancing phagocytic activity. Materials and methods Water bath control and mEHT were used to compare the enhancement of liposome-encapsulated doxorubicin (Lipodox ® ) uptake by cancer cells. Cancer cells were made visible by doxorubicin fluorescence to investigate drug uptake. Viable cell yield was determined via the Trypan Blue exclusion method. Various substrates were used to investigate the mechanism of drug-uptake enhancement. The murine colon carcinoma model, CT26, was used to confirm the tissue infiltration of Lipodox ® and its therapeutic effect. Results mEHT treatment showed a significant enhancement of Lipodox ® uptake of doxorubicin fluorescence compared with 37°C or 42°C water bath treatment. Tumor tissue sections also confirmed that mEHT treatment achieved the highest doxorubicin concentration in vivo (1.44±0.32 µg/g in mEHT group and 0.79±0.32 µg/g in 42°C water bath). Wortmannin was used to inhibit the macropinocytosis effect and 70 kDa dextran-FITC served as uptake substance. The uptake of dextran-FITC by cancer cells significantly increased after mEHT treatment whereas such enhancement was significantly inhibited by wortmannin. Conclusion The result showed mEHT-induced particle-uptake through macropinocytosis. mEHT-enhanced uptake of Lipodox ® may amplify the therapeutic effect of liposomal drugs. This novel finding warrants further clinical investigation.

Modulated electro-hyperthermia (meHt) is a form of mild hyperthermia (Ht) used for cancer treatment. the principle utility of Ht is the ability not only to increase cell temperature, but also to increase blood flow and associated pO 2 to the microenvironment. While investigational evidence has shown the unique ability of meHt to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional Ht. there is dissension as to what allows meHt to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. for this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by meHt. to evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10 min. mark): escalation from 25 °C to 37 °C Phase II (10 min. mark to 15 min. mark): escalation from 37 °C to 42 °C Phase III (15 min. mark to 45 min. mark): maintenance at 42 °C Combinations of mEHT at 18 W power, mEHT at 7.5 W power, water bath, and incubator were applied to each of the three phases. power output was recorded per second and calculated as average power per second. total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 ± 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 ± 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 ± 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 °C or incubator at 37 °C, resulted in nearly identical apoptosis rates, 26 ± 4.4% and 25.9 ± 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18 W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18 W/sec), apoptosis was limited during temperature maintenance with lower power (7.5 W/sec). This presents that neither maintenance of 42 °C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment. Hyperthermia (HT) is a method of cancer treatment in which patients are subjected to supra-normal body temperatures, and is often used in conjunction with radiotherapy or chemotherapy 1,2. Modulated electro-hyperthermia (mEHT) is a loco-regional hyperthermia method utilizing electromagnetic current at