Impact of Prolonged Fraction Delivery Times Simulating IMRT on Cultured Nasopharyngeal Carcinoma Cell Killing

Zheng, Xuelian; Chen, Longhua; Wang, Wenjun; Ye, Feng; Liu, Jia-Bing; Li, Qisheng; Sun, Hen-Wen

doi:10.1016/j.ijrobp.2010.07.005

Cited by 28 publications

(24 citation statements)

References 36 publications

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“…Treatment time may be important for the patient's comfort as well astumorcontrol. In an in vitro study on nasopharyngeal carcinoma cell lines, Zheng et al showed that longer fraction delivery time results in less tumor cell kill, probably due to sublethal damage repair during the irradiation [74]. However, with HT, although the full treatment may take up to 5-10 minutes, each slice of tissue is treated with a very high dose rate, thus preventing sublethal damage repair by excluding any dose-rate effect (Fig.…”

Section: The Limitations Of Htmentioning

confidence: 99%

The Potential of Helical Tomotherapy in the Treatment of Head and Neck Cancer

et al. 2013

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A decade after its first introduction into the clinic, little is known about the clinical impact of helical tomotherapy (HT) on head and neck cancer (HNC) treatment. Therefore, we analyzed the basics of this technique and reviewed the literature regarding HT's potential benefit in HNC. The past two decades have been characterized by a huge technological evolution in photon beam radiotherapy (RT). In HNC, static beam intensitymodulated radiotherapy (IMRT) has shown superiority over three-dimensional conformal RT in terms of xerostomia and is considered the standard of care. However, the next-generation IMRT, the rotational IMRT, has been introduced into the clinic without any evidence of superiority over static beam IMRT other than being substantially faster. Of these rotational techniques, HT is the first system especially developed for IMRT in combination with image-guided RT. HT is particularly promising for the treatment of HNC because its sharp dose gradients maximally spare the many radiosensitive organs at risk nearby. In addition, HT's integrated computed tomography scan assures a very precise dose administration and allows for some adaptive RT. Because HT is specifically developed for IMRT in combination with (integrated) imageguidance, it allows for precise dose distribution ("dose painting"), patient setup, and dose delivery. As such, it is an excellent tool for difficult HNC irradiation. The literature on the clinical results of HT in HNC all show excellent short-term (Յ2 years) results with acceptable toxicity profiles. However, properly designed trials are still warranted to further substantiate these results. The Oncologist 2013;18:697-706 Implications for Practice: This article highlights the advantages of helical tomotherapy in the treatment of head and neck cancer as it combines three recent evolutions and challenges in radiotherapy in an integrated system. (1) A rotational IMRT technique that is very efficient in generating homogeneous dose distributions to the target volume while sparing the organs at risk more precisely than conventional IMRT approaches. (2) Three-dimensional image guidance permits a more precise administration of the radiation than the classical two-dimensional imaging. This allows for reduction of the safety margins, which in turn, reduces toxicity. (3) Adaptive radiotherapy is still very labor intensive and no software is able to provide daily online adaptation. Tomotherapy offers a platform that allows for pioneering attempts at adaptive radiotherapy with the possibility of recalculating the administered treatment based on the daily CT scan. Properly designed trials are still warranted to further substantiate the results of this promising treatment modality. INTRODUCTIONDespite major progress in locoregional control, the treatment outcomes of locoregionally advanced head and neck cancer (HNC) remain poor, with a 5-year survival rate of approximately 35% due to the development of distant metastases, locoregional failures, second primaries, and/or comorbidities [1][...

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Section: The Limitations Of Htmentioning

confidence: 99%

The Potential of Helical Tomotherapy in the Treatment of Head and Neck Cancer

et al. 2013

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“…Late-responding normal tissue with a lower α/β ratio showed a stronger ability to demonstrate sub-lethal damage repair (SLDR) compared to acute-responding normal tissue. When the fraction delivery time was prolonged, SLDR occurred during the inter-subfraction615. Our results revealed that acute- and late-responding normal tissues have different sensitivities to changes in FDT (Fig.…”

Section: Discussionmentioning

confidence: 63%

“…Previous studies have shown that prolonged FDTs can cause a significant decrease in cell killing in tumor cells with a low α/β ratio, but only slight decrease, without significance, in tumor cells with a high α/β ratio1521. We also irradiated nasopharyngeal carcinoma cell lines CNE1 and CNE2 with the same dosing schedules that had been used for normal cells.…”

Section: Discussionmentioning

confidence: 99%

Late-responding normal tissue cells benefit from high-precision radiotherapy with prolonged fraction delivery times via enhanced autophagy

Yao

Zheng

Xie

et al. 2015

Sci Rep

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High-precision radiotherapy (HPR) has established its important role in the treatment of tumors due to its precise dose distribution. Given its more complicated delivery process, HPR commonly requires more fraction delivery time (FDT). However, it is unknown whether it has an identical response of prolonged FDT on different normal tissues. Our results showed that fractionated irradiation with prolonged FDTs (15, 36, and 50 minutes) enhanced cell surviving fractions for normal tissue cells compared with irradiation with an FDT of 2 minutes. However, the late-responding normal cell line HEI-OC1 was more responsive to prolonged FDTs and demonstrated higher surviving fractions and significantly decreased apoptosis and DNA damage compared to the acute-responding normal cell line HaCaT. Increased autophagy mediated via the ATM-AMPK pathway was observed in HEI-OC1 cells compared with HaCaT cells when irradiated with prolonged FDTs. Furthermore, treatment with the autophagy inhibitor 3-MA or ATM inhibitor KU55933 resulted in enhanced ROS accumulation and attenuation of the effect of prolonged FDT-mediated protection on irradiated HEI-OC1 cells. Our results indicated that late-responding normal tissue cells benefitted more from prolonged FDTs compared with acute-responding tissue cells, which was mainly attributed to enhanced cytoprotective autophagy mediated via the ATM/AMPK signaling pathway.

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“…[5][6][7] This can be accomplished in the clinic by adjusting the DRs in the new treatment machines capable of IMRT. Increasing the DR twice will half the duration of each fraction.…”

Section: Discussionmentioning

confidence: 99%