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Michael Baumann

Publications and source records attributed to Michael Baumann.

At least 37 records · Page 2Linked to original sources
PubMed2005

Recovery from sublethal damage during fractionated irradiation of human FaDu SCC.

BACKGROUND AND PURPOSE: The present study addresses whether recovery of sublethal damage in tumours may change during fractionated irradiation in FaDu human squamous cell carcinoma and whether such an effect might contribute to the pronounced time factor of fractionated irradiation previously found in this tumour. PATIENTS AND METHODS: FaDu tumours were transplanted s.c. into the right hind leg of NMRI nu/nu mice. Single doses or 2, 4, and 8 equal fractions in 3.5 days were applied in previously unirradiated tumours and after priming with 18 fractions of 3 Gy in 18 or 36 days. All irradiations were given under clamp hypoxic conditions. Experimental endpoints were tumour control dose 50% (TCD50) and alpha/ beta values without and after priming. RESULTS: Without priming TCD50 increased with increasing number of fractions from 38.8 Gy (95% CI 35;45) after single dose irradiation to 54.0 Gy (42;57) after 8 fractions. No increase in TCD50 when given in 1, 2, 4, or 8 fractions in 3.5 days was found after priming with 18 3-Gy fractions in 18 and 36 days. After priming with 18 fractions in 18 days TCD50 remained constant at 25 Gy and after priming with 18 fractions in 36 days at 42 Gy. The alpha/beta ratio without priming was 68 Gy (42;127). After fractionated irradiation with 18 3-Gy fractions in 18 and 36 days the alpha/beta ratio increased to 317 Gy (38; infinity) and to infinite, respectively. CONCLUSIONS: Our results indicate that clonogenic cells in FaDu tumours lose entirely their capacity to recover from sublethal radiation damage during fractionated irradiation. Therefore, an increased repair capacity as an explanation for the pronounced time factor of fractionated irradiation in this tumour can be ruled out.

Animals↗
PubMed2005

Does heterogeneity of pimonidazole labelling correspond to the heterogeneity of radiation-response of FaDu human squamous cell carcinoma?

BACKGROUND AND PURPOSE: Pimonidazole is a marker for hypoxic cells which are radioresistant and thereby important for the outcome of radiotherapy. The present study evaluates heterogeneity in pimonidazole binding within and between tumours and relates the results to the heterogeneity of radiation response in the same tumour cell line. MATERIALS AND METHODS: FaDu, a poorly differentiated human squamous cell carcinoma line, was transplanted subcutaneously into the right hind-leg of NMRI nude mice. Tumours were irradiated with graded single doses either under ambient or clamped blood flow conditions and local tumour control was evaluated after 120 days. Complete dose-response curves for local tumour control were generated and the slope, a measure of heterogeneity of radiation response, was determined. In parallel, 12 unirradiated tumours were examined histologically. Seven serial 10 microm cross-sections per tumour were evaluated using fluorescence microscopy and computerised image analysis to determine the pimonidazole hypoxic fraction (pHF). Heterogeneity in pHF was quantified by its coefficient of variation (CV). Poisson-based model calculations considering the intertumoural heterogeneity of pHF were performed and the slopes of the predicted and the observed dose-response curves were compared. RESULTS: The mean pHF was 11% [CV 50%] when one central section per tumour was evaluated. Measurements of multiple sections per tumour resulted in a mean pHF of 12% [CV 46%] (P=0.7). Intertumoural heterogeneity in pHF was more pronounced than heterogeneity in individual tumours by a factor of 2. Model calculations based on the variability in pHF resulted in similar slopes of the dose-response curve for local tumour control in comparison with the observed slope when the heterogeneity in an unknown and arbitrarily chosen additional radiobiologically relevant parameter, in this example clonogen density, was taken into account. CONCLUSIONS: While the average pimonidazole hypoxic fraction in FaDu tumours corresponds well to the radiobiological hypoxic fraction, the variability of pHF in FaDu tumours was not sufficient to explain the heterogeneity of radiation response in the same tumour line. Information on at least one additional parameter is expected to substantially enhance the predictive power of histological markers of tumour hypoxia.

Animals↗
PubMed2005

Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway.

BACKGROUND AND PURPOSE: In the context of EGFR-targeting strategies we investigated autocrine/paracrine factors leading to in vitro radioresistance of K-Ras mutated tumor cells through activation of EGFR mediated signal transduction. PATIENTS AND METHODS: Ras mutated (Rasmt) and normal Ras (Raswt) presenting human tumor cell lines were used to analyze the potential of conditioned media (CM) of both cell types to mediate radioresistance and to activate EGFR-signaling cascades. Therefore, clonogenic assays as well as SDS-PAGE combined with immunoblotting was performed. Additionally, Ras-mutated cells were transfected with K-Ras-siRNA to investigate, how downregulation of mutated K-Ras affects secretion of EGFR-ligands, stimulation of EGFR-signaling and modulation of radiation response. RESULTS: TGFalpha, Amphiregulin (ARG) and CM from Rasmt cells (Rasmt-CM) resulted in an increased clonogenic survival of irradiated Raswt cells. Both, EGFR ligands as well as Rasmt-CM led to a strong phosphorylation of EGFR and activation of downstream pathways, i.e. PI3K-AKT. However, neutralization of TGFalpha or ARG in Rasmt-CM led to a marked reduction of P-AKT. Furthermore, Rasmt-CM from K-Ras-siRNA transfected Rasmt-cells markedly inhibited phosphorylation of AKT in Raswt cells and enhanced radiation sensitivity of A549 cells transfected with the siRNA. CONCLUSION: The data suggest that constitutively upregulated autocrine/paracrine secretion of EGF receptor ligands, especially ARG from K-Ras mutated cells, mediates radioresistance in Rasmt-cells through stimulation of EGFR-PI3K-AKT pathway.

Amphiregulin↗
PubMed2005

Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation.

BACKGROUND AND PURPOSE: Inhibition of repopulation and enhanced reoxygenation has been suggested to contribute to improvement of local tumour control after fractionated irradiation combined with inhibitors of the epidermal growth factor receptor (EGFR). The present study addresses this hypothesis in FaDu human squamous cell carcinoma. For this tumour model marked repopulation and incomplete reoxygenation during fractionated irradiation has previously been demonstrated. Furthermore, the anti-EGFR monoclonal antibody C225 has been shown to significantly improve the results of fractionated irradiation in this tumour. MATERIALS AND METHODS: FaDu tumours in nude mice were irradiated with 18 fractions in 18 days (18f/18d) or 18 fractions in 36 days (18f/36d). Three Gy fractions were given either under ambient or under clamp hypoxic conditions. C225 or carrier was applied four times during the course of treatment. Fractionated irradiations were followed by graded top-up doses to obtain complete dose-response curves for local tumour control. Tumour control dose 50% (TCD50) was determined at day 120 after end of treatment. RESULTS: Significant repopulation and reoxygenation occurred during fractionated irradiation of FaDu tumours (P-values between 0.028 and <0.001). Application of C225 significantly decreased TCD50 for 18f/36d under ambient conditions (P=0.04). Bootstrap analysis revealed decreased repopulation and increased reoxygenation after application of C225 (P=0.06 for the combined effect). This was further corroborated by a significant effect of C225 on the 'repopulated' dose under ambient conditions which is influenced by both, reoxygenation and repopulation (P=0.012). CONCLUSIONS: Our study provides evidence that both decreased repopulation as well as increased reoxygenation contribute to the improvement of local control after targeting of EGFR by C225 during fractionated irradiation of FaDu tumours.

Animals↗
PubMed2005

Kinetics of EGFR expression during fractionated irradiation varies between different human squamous cell carcinoma lines in nude mice.

BACKGROUND AND PURPOSE: Preclinical and clinical data indicate that high pretherapeutic EGFR expression is associated with poor local tumour control, possibly caused by a high repopulation rate of clonogenic cells during radiotherapy in these tumours. Previous data reported from our laboratory showed a correlation between EGFR expression and acceleration of repopulation in poorly differentiated FaDu human squamous cell carcinoma (SCC) during fractionated irradiation. To test whether this is a general phenomenon, two further SCC were investigated in the present study. PATIENTS AND METHODS: GL and UT-SCC-14, two moderately well differentiated and keratinising hSCC, were grown as xenografts in nude mice. Functional data on the repopulation kinetics during fractionated irradiation for these tumour models have been previously determined. The expression of EGFR during fractionation was analysed by immunohistochemistry. Endpoints were the membrane-staining score and the proportion of EGFR-positive cells (EGFR labelling index). RESULTS: Different kinetics of EGFR expression during fractionated RT were found. In UT-SCC-14, EGFR staining score and labelling index increased significantly during radiotherapy. In GL SCC, the EGFR expression was unchanged. Both tumours are characterized by a small but significant repopulation rate during radiotherapy. CONCLUSIONS: The expression of EGFR may change significantly during fractionated irradiation. No clear correlation between EGFR expression and the repopulation kinetics of clonogenic tumour cells during fractionated irradiation was found. The changes in EGFR expression during irradiation warrant further investigation on their prognostic implications and on their importance for therapeutic interventions.

Animals↗
PubMed2005

Low-dose hyperradiosensitivity of human glioblastoma cell lines in vitro does not translate into improved outcome of ultrafractionated radiotherapy in vivo.

PURPOSE: Low dose hyperradiosensitivity (HRS) has been observed in HGL21- and T98G human glioblastoma cells in vitro. The present study investigates whether these effects translate into improved outcome of ultrafractionated irradiation (UF) in vivo. MATERIAL AND METHODS: T98G or HGL21 were transplanted on the hind leg of nude mice. Tumours were irradiated with UF (3 fractions of 0.4 Gy per day, interval 4 h, 7 days per week) or with conventional fractionation (CF; 1 fraction of 1.68 Gy per day, 5 days per week) over 2 or 4 weeks in HGL21 and 2,4 or 6 weeks in T98G. In HGL21, graded top-up doses under clamped hypoxia were applied after 4 weeks of fractionated irradiation. Additional groups of animals were irradiated with single doses under clamp hypoxic conditions with or without whole body irradiation (WBI) before tumour transplantation. Experimental endpoints were growth delay (time to 5-fold starting volume, GD(V5)) and local tumour control. RESULTS: In T98G tumours median relative GD(V5) was 1.2 [95% C.I. 0.96; 8] in the CF and 0.8 [0.7; 1.02] in the UF arm (p = 0.009) indicating that ultrafractionation is less efficient than conventional fractionation. The TCD50 value of 33.5 Gy [22; 45] after UF was higher than TCD50 of 23.6 Gy [16; 31] after CF (p = 0.15). In HGL21 the median relative GD(V5) was not significantly different between CF and UF. The top-up TCD50 value of 16.1 Gy [95% C.I. 9; 23 Gy] after CF was significantly lower than the corresponding value of 33.2 Gy [23; 44] after UF irradiation (p = 0.007), indicating a higher efficacy of CF compared to UF. CONCLUSION: The results on human T98G and HGL21 glioblastoma do not support the hypothesis that HRS in vitro translates into improved outcome of ultrafractionated irradiation in vivo.

Animals↗
PubMed2005

Comparative analysis of antigen specificities in the monomeric and dimeric fractions of intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) preparations are derived from the pooled plasma of thousands of healthy donors and contain a complex mix of antibodies. Depending on the formulation, IVIG preparations contain variable amounts of monomeric and dimeric IgG. The biological and therapeutic significance of these IVIG fractions is still ill defined. Kinetic analysis of monomeric and dimeric IgG isolated by size-exclusion chromatography revealed a stable monomeric versus an unstable dimeric IgG fraction tending to dissociation. Biochemical analysis by 2D gel electrophoresis and isotype analysis showed no significant differences between the fractions. In contrast, comparative analysis by immunodot, ELISA, FACS, and immunohistology of monomeric and dimeric IgG fractions showed a preferential reactivity of the dimeric IgG on a variety of both self-antigens and exoantigens.

Animals↗
PubMed2004

Radiosensitization of Ras-mutated human tumor cells in vitro by the specific EGF receptor antagonist BIBX1382BS.

BACKGROUND AND PURPOSE: To investigate the cellular and molecular consequences of antagonizing radiation-induced EGFR-activation in vitro. PATIENTS AND METHODS: The effect of the EGFR tyrosine kinase inhibitor BIBX1382BS on radiation sensitivity was determined after single- and fractionated-dose irradiation in human cell lines of bronchial carcinoma (A549), breast adeno-carcinoma (MDA-MB-231), pharyngeal squamous-cell carcinoma (FaDu), squamous-cell carcinoma of cervix (HTB-35) as well as normal (HSF-7) and transformed (HH4-DED) human skin fibroblasts. Applying immuno-precipitation and western blotting pattern of radiation-dependent activation of different components of EGFR-signaling after pre-treatment with and without BIBX1382BS or other tyrosine kinase inhibitors was analyzed. RESULTS: Autophosphorylation of EGFR which occurred 1-5 min after irradiation (IR, 2 Gy) or treatment with EGF (100 ng/ml) could be inhibited in all cells tested by pre-treatment with BIBX1382BS for 30 min. Combination of drug treatment with fractionated irradiation (4x2 Gy) led to a strong radiosensitizing effect in Ras-mutated A549 and MDA-MB-231 cells, but not in normal Ras presenting cell lines FaDu and HTB-35 or normal and transformed human skin fibroblasts. Both BIBX1382BS as well as the PI3 kinase inhibitor LY294002 led to a blockage (for A549 cells) or reduction (for FaDu cells) of radiation-induced P-AKT. In contrast to FaDu cells, treatment of A549 cells with LY294002 resulted in a significant decrease of post-irradiation survival of A549 cells. Furthermore, only in Ras-mutated cells, but not in normal Ras cells clonogenic survival and phosphorylation of AKT was sensitive to pre-treatment with TGF-alpha-neutralizing antibody indicating an important role of TGF-alpha in regulating radiation-induced EGFR signaling. CONCLUSIONS: Enhancement of radiation sensitivity by the specific EGFR-tyrosine kinase inhibitor BIBX1382BS is not generally achieved in human tumor cells, but depends most likely on the Ras genotype of the cell lines tested.

Adenocarcinoma↗
PubMed2004

In vivo verification of electron beam energy by patient exit dose and optical density of portal films.

BACKGROUND AND PURPOSE: The depth-dose curve of electron beams is mainly determined by their energy. For accelerators with scatter foils, the electron energy can, in principle, be verified by measuring the amount of the contaminating photons. This paper investigates whether exit dose measurements and evaluations of the optical density of portal films can be used to verify the energy of the electron beam in a clinically relevant setting. MATERIAL AND METHODS: During irradiation of the head and neck region of an Alderson-Rando phantom with 6- to 21-MeV electron beams, the exit dose rates behind the phantom and the dose rates at the position of a film cassette were measured. The optical density of films (EC film/EC-L Regular and EC-L Fast cassettes, Eastman Kodak Comp., Rochester, NY, USA) exposed to beams of different energies was evaluated. RESULTS: The exit and the cassette dose rates showed a steep increase with increasing electron energy. Due to its density behavior, the film with both types of cassettes failed to generate images for lower electron energies (6 and 9 MeV) but presented a strong ascent of the optical density-until reaching the saturation-with increasing electron energy. CONCLUSION: Measurements of the exit dose and evaluations of the optical density of portal films can be used to verify and document the energy of electron beams during radiotherapy.

Artifacts↗
PubMed2004

Effect of the hypoxic cell sensitizer isometronidazole on local control of two human squamous cell carcinomas after fractionated irradiation.

BACKGROUND AND PURPOSE: Hypoxia of clonogenic tumor cells is a major reason for radioresistance and hence local failure in radiotherapy. The objective of the present study was to test the efficacy of the hypoxic cell sensitizer isometronidazole (ISO) during fractionated irradiation in two different human squamous cell carcinomas. MATERIAL AND METHODS: Local control was evaluated for FaDu (radiobiological hypoxic fraction [rHF] 7%) and GL tumors (rHF 0.1%) after single-dose (SD) irradiation under ambient conditions and after 30 fractions within 6 weeks (30 f/6 w). ISO was applied 60 min before SD irradiation at a concentration of 100 mg/kg body weight (b.w.) or 750 mg/kg b.w. in both tumors. During fractionated irradiation, ISO was applied daily 60 min before each fraction (100 mg/kg b.w., in FaDu also 750 mg/kg b.w.). RESULTS: 100 mg/kg b. w. ISO did not improve local control after SD irradiation or 30 f/6 w in both tumor models. Application of 750 mg/kg b. w. ISO significantly decreased the SD-TCD(50) in FaDu tumors (dose-modifying factor [DMF] = 1.2; p = 0.01) but not in the better oxygenated GL tumor. ISO at 750 mg/kg b.w. also significantly improved local control of FaDu tumors after 30 fractions in 6 weeks (DMF = 1.2; p = 0.01), indicating that hypoxic clonogenic cells in FaDu tumors are not only present before start of irradiation but also limit the efficacy of treatment during a fractionated course of radiotherapy. CONCLUSION: ISO at a concentration of 750 mg/kg b.w. shows an efficacy as a hypoxic cell sensitizer in severely hypoxic FaDu tumors but not in less hypoxic GL tumors. This supports the principle of hypoxic cell sensitization and improvement of local control of hypoxic tumors by nitroimidazole derivatives. However, doses of 750 mg/kg b. w. before each fraction may be difficult to achieve in the clinical situation. This, in light of the fact that other well-tolerable hypoxic cell sensitizers such as nimorazole with clinically proven efficacy at daily oral doses of < 3 g are available, limits the potential usefulness of ISO for radiation oncology.

Animals↗
PubMed2004

Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multi-institutional research project.

BACKGROUND: Recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation. MATERIAL AND METHODS: The present article will introduce a multi-institutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Würzburg, Germany. RESULTS: The joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined. CONCLUSION: Besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation.

Animals↗
PubMed2004

Ribosomal p70S6K basal activity increases upon induction of differentiation of myelomonocytic leukemic cell lines HL60, AML14 and MPD.

The role of ribosomal p70S6K in the cell cycle has been studied extensively, and it is known that this enzyme is crucial for cell advancement through G(1). Conversely, the participation of p70S6K in cell differentiation is not well understood. We have studied the response of p70S6K to the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in three differentiation-capable leukemic cell lines (MPD, AML-14 and HL-60) and in normal mature neutrophils. Immature leukemic cells starved for 16 h showed a robust ( approximately 3.5-fold over controls) p70S6K phosphorylation on T(421)/S(424) residues in response to an acute (5 min) 10 nM GM-CSF stimulation. On the other hand, cells that had been induced to differentiate and express granulocytic phenotypes, showed an increased ( approximately 6-fold) basal level of p70S6K T(421)/S(424) phosphorylation over immature cells, as well as an increased baseline tyrosyl phosphorylation of the GM-CSF receptor beta subunit (GM-CSF.Rbeta). However, the differentiated cells displayed a weak ( approximately 1.4-fold over controls) response to GM-CSF even at prolonged incubation times (20 min). In vitro p70S6K enzymatic activity paralleled p70S6K T(421)/S(424) phosphorylation in both high basal, unstimulated, levels in immature cells and a low degree of response to GM-CSF. Lastly, peripheral blood mature neutrophils had low basal GM-CSF.Rbeta and p70S6K activity, with both parameters being robustly stimulated following addition of GM-CSF, a situation in contrast with the cell lines, indicative perhaps of their incomplete terminal differentiation. In summary, these findings show the increase in basal phosphorylation of p70S6K upon granulocytic differentiation of myeloid leukemic cells and their responses to GM-CSF that are closely paralleled with tyrosyl phosphorylation of its receptor, and help in pointing to specific cell signaling molecules that are different in leukemic blasts from normal leukocytes.

Cell Differentiation↗
PubMed2004

Molecular targeting in radiotherapy of lung cancer.

Molecular targeting is a promising option to increase the radiation response of tumours and to decrease normal tissue reactions, i.e. to achieve therapeutic gain. Molecular targeting substances in themselves are not curative while radiation is a highly efficient cytotoxic agent, with local recurrences often occurring from only few surviving clonogenic cells. High-dose radiotherapy therefore offers optimal conditions to evaluate the potential of specific biology-driven drugs for oncology. This review summarises the current status of preclinical and clinical research on combined radiation with examples of molecular targeting substances relevant for the treatment of NSCLC (EGFR, COX-2, VEGFR, KGF, TGF-beta, BBI).

Angiogenesis Inhibitors↗
PubMed2004

Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: a literature review.

Late complications are one of the major factors limiting radiotherapy treatment, and their treatment is not codified. Hyperbaric oxygen (HBO) has been used in combination with radiotherapy for over half a century, either to maximise its effectiveness or in an attempt to treat late complications. In this latter case, retrospective trials and case reports are prevailing in literature. This prompted European Society for Therapeutic Radiotherapy and Oncology and European Committee for Hyperbaric Medicine to organise a consensus conference in October 2001, dealing with the HBO indications on radiotherapy for the treatment and prevention of late complications. This updated literature review is part of the documents the jury based its opinion on. A systematic search was done on literature from 1960 to 2004, by only taking into account the articles that appeared in peer review journals. Hyperbaric oxygen treatment involving complications to the head and neck, pelvis and nervous system, and the prevention of complications after surgery in irradiated tissues have been studied. Despite the small number of controlled trials, it may be indicated for the treatment of mandibular osteoradionecrosis in combination with surgery, haemorrhagic cystitis resistant to conventional treatments and the prevention of osteoradionecrosis after dental extraction, whose level of evidence seems to be the most significant though randomised trials are still necessary. The other treatment methods are also outlined for each location.

Humans↗
PubMed2004

Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results.

BACKGROUND AND PURPOSE: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. MATERIALS AND METHODS: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. RESULTS: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. CONCLUSIONS AND OUTLOOK: Further investigations at all levels of the translational research chain exploring the mechanisms of EGFR inhibition in the context of radiotherapy are needed to fully exploit the potential of such combinations and to develop predictive tests that direct their use.

Combined Modality Therapy↗