In vitro evaluation of photon and carbon ion radiotherapy in combination with chemotherapy in glioblastoma cells

Combs, Stephanie E.; Zipp, Lisa; Rieken, Stefan; Habermehl, Daniel; Brons, Stefan; Winter, Marcus; Haberer, Thomas; Debus, Jürgen; Weber, Klaus-Josef

doi:10.1186/1748-717x-7-9

Cited by 51 publications

(35 citation statements)

References 17 publications

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“…Additionally, having already shown that a combination of gemcitabine chemotherapy and photon irradiation benefits resectability [4], it was another aim to evaluate the effects of a combination of gemcitabine and carbon ions and in this study we have found out that additive effects, as well as a slight radiosensitizing effect in one cell line, can be achieved for this combination. Similar effects have already been confirmed at our department for glioblastoma cell lines using a combination of carbon ion irradiation and several chemotherapeutic agents including gemcitabine [27]. …”

Section: Discussionsupporting

confidence: 70%

In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines

Shafie

Habermehl

Rieken

et al. 2013

Journal of Radiation Research

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Background: Pancreatic cancer is the fourth leading cause of cancer deaths, being responsible for 6% of all cancer-related deaths. Conventional radiotherapy with or without additional chemotherapy has been applied in the past in the context of neoadjuvant or adjuvant therapy concepts with only modest results, however new radiation modalities, such as particle therapy with promising physical and biological characteristics, present an alternative treatment option for patients with pancreatic cancer. Up until now the raster scanning technique employed at our institution for the application of carbon ions has been unique, and no radiobiological data using pancreatic cancer cells has been available yet. The aim of this study was to evaluate cytotoxic effects that can be achieved by treating pancreatic cancer cell lines with combinations of X-rays and gemcitabine, or alternatively with carbon ion irradiation and gemcitabine, respectively. Materials and Methods: Human pancreatic cancer cell lines AsPC-1, BxPC-3 and Panc-1 were irradiated with photons and carbon ions at various doses and treated with gemcitabine. Photon irradiation was applied with a biological cabin X-ray irradiator, and carbon ion irradiation was applied with an extended Bragg peak (linear energy transfer (LET) 103 keV/μm) using the raster scanning technique at the Heidelberg Ion Therapy Center (HIT). Responsiveness of pancreatic cancer cells to the treatment was measured by clonogenic survival. Clonogenic survival curves were then compared to predicted curves that were calculated employing the local effect model (LEM). Results: Cell survival curves were calculated from the surviving fractions of each combination experiment and compared to a drug control that was only irradiated with X-rays or carbon ions, without application of gemcitabine. In terms of cytotoxicity, additive effects were achieved for the cell lines Panc-1 and BxPC-3, and a slight radiosensitizing effect was observed for AsPC-1. Relative biological effectiveness (RBE) of carbon ion irradiation ranged from 1.5–4.5 depending on survival level and dose. Sensitizer enhancement ratio (SER) values calculated at 10% cell survival ranged from 1.24–1.66, depending on cell line, gemcitabine dose and irradiation modality. Experimentally ascertained survival curves matched those predicted by LEM-calculation. Conclusion: Our experiments have shown a combined treatment of irradiation and chemotherapy with gemcitabine to be a good means of achieving additive cytotoxic effects on pancreatic cancer cell lines. The data generated in this study will serve as radiobiological basis for further preclinical and clinical studies.

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Section: Discussionsupporting

confidence: 70%

In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines

Shafie

Habermehl

Rieken

et al. 2013

Journal of Radiation Research

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“…Thus, it is possible that concomitant use of cisplatin will also increase the efficacy of carbon ion radiotherapy. However, preclinical data regarding the combined effect of carbon ions and cisplatin are limited; only a few small-scale studies have been conducted (Supplementary Table 1)78910. Data from these studies are unclear as to whether the cell killing effect of carbon ions plus cisplatin is synergistic.…”

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confidence: 99%

“…The combined effect of X-rays and cisplatin has been extensively studied in the preclinical setting; however, there are no firm conclusions as to whether the effects are synergistic or purely additive because results vary widely from marked synergism to none at all (Supplementary Table 1)89101112131415161718192021. Furthermore, the presence/absence of synergism is inconsistent even between studies using the same cell lines (i.e., Agoni et al vs. Flentje et al .…”

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confidence: 99%

Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin

Kobayashi

Oike

Shibata

et al. 2017

Sci Rep

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In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4′,6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.

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“…Patients with SE < 30 days had a predicted better 5-year survival rate that was greater than 20%. The effect of sequential TRT could be reduced by prolonged chemotherapy, which might result in the regeneration of drug-resistant tumor cells (Brade and Tannock, 2006;Combs et al, 2012).…”

Section: Modalities and Timing Of Radiotherapymentioning

confidence: 99%

Effect of radiotherapy on the treatment of patients with extensive stage small cell lung cancer

Wu¹,

Wang²,

Wang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Small cell lung cancer (SCLC) is an aggressive disease, in which more than 80% of patients present distant metastases at the time of first diagnosis. Chemotherapy is considered as the main treatment of extensive disease of SCLC (ED-SCLC), while the role of radiotherapy in the treatment of ED-SCLC is controversial. A case-control study was undertaken of patients diagnosed as ED-SCLC between 2004 and 2010. Fifty-eight patients with overall survival (OS) over 1 year were chosen, and another 58 patients with OS less than 1 year were selected as the control group, with the age, gender, metastasis or no metastasis of the liver, and the response after the first line of chemotherapy matched. The 1-year, 2-year, 3-year, and median OS of the 75 ED-SCLC patients who received radiation were 81.47, 29.89, 22.77%, and 17 months, respectively, and were 61.18, 23.53, 0%, and 16 months, respectively, for patients who did not receive radiation. The χ 2 test and odds ratio (OR) estimate demonstrated that these differences were statistically significant (χ 2 = 6.38, P = 0.0116; OR = 2.74, 95% confidence interval = 1.24-6.05). These results show that radiotherapy also plays a role in responding patients with extensive stage of SCLC.

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In vitro evaluation of photon and carbon ion radiotherapy in combination with chemotherapy in glioblastoma cells

Cited by 51 publications

References 17 publications

In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines

In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines

Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin

Effect of radiotherapy on the treatment of patients with extensive stage small cell lung cancer

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