The schemes of dose fractionation play an important role in tumor radiotherapy. We used mathematical methods to describe the process of tumor cells evolution during radiotherapy, trying to find how the schemes of dose fractionation affect tumor cells. In clinical radiobiology, linear-quadratic (LQ) model is frequently used to describe radiation effects of tumor cells. We integrated LQ model with effect of oxygen, and with the phenomenon of repopulation and reoxygenation in the theory of radiation biology. While we considered the disappearing progress of doomed cells in tumor, we established the mathematical model of tumor evolution in radiotherapy. We simulated some common treatment schedules, and studied the change role of tumor cells during radiotherapy. These results can serve for the optimization of dose fractionation scheme based on tumor radiobiological characteristics.
Cell Growth Processes ; radiation effects ; Dose Fractionation ; Humans ; Models, Theoretical ; Neoplasms ; pathology ; physiopathology ; radiotherapy ; Radiobiology

OBJECTIVETo investigate the effect of mannatide injection (MI) in enhancing the efficacy of radiotherapy in two therapeutic schedules in mice bearing Lewis lung cancer.

METHODSC57BL/6 mice bearing Lewis lung cancer xenograft were assigned randomly into control group, fractionated schedule (FS) group, nonfractionated schedule (NFS) group, MI group, FS+MI group, and NFS+MI group (n=10). MI (4.5 mg/kg) or saline was given intraperitoneally for 14 consecutive days in the corresponding groups. Radiation with 8 MeV electron beam was delivered in a single 4 Gy dose in NFS and in 4 fractions (total dose 4 Gy) in FS. Tumor inhibition rate and the spleen and thymus index were calculated after the treatments.

RESULTSMI significantly enhanced the efficacy of radiotherapy with a tumor inhibition rate reaching 70% in FS+MI group (P<0.01). FS resulted in a significantly higher tumor inhibition rate than NFS (P<0.05), but the rates were comparable between FS+MI and NFS+MI groups. The spleen index and thymus indices were significantly higher in FS+MI and NFS+MI groups than in FS and NFS groups (P<0.05).

CONCLUSIONMI can enhance the efficacy of radiotherapy with different therapeutic schedules in mice bear Lewis lung cancer, and MI plus fractionated radiation produces the optimal effect.

Animals ; Biological Products ; therapeutic use ; Carcinoma, Lewis Lung ; drug therapy ; radiotherapy ; Combined Modality Therapy ; Dose Fractionation ; Dose-Response Relationship, Radiation ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Radiation-Sensitizing Agents ; therapeutic use ; Streptococcus

PURPOSE: High dose definitive radiation therapy (RT) alone is recommended to patients with cT1-3N0 non-small cell lung cancer, who are unfit for surgery or stereotactic RT. This study was conducted to evaluate the clinical outcomes and cost-effectiveness following RT alone using two different modest hypofractionation dose schemes. MATERIALS AND METHODS: Between 2001 and 2014, 124 patients underwent RT alone. From 2001 till 2010, 60 Gy in 20 fractions was delivered to 79 patients (group 1). Since 2011, 60 Gy in 20 fractions (group 2, 20 patients), and 60 Gy in 15 fractions (group 3, 25 patients) were selectively chosen depending on estimated risk of esophagitis. RESULTS: At follow-up of 16.7 months, 2-year rates of local control, progression-free survival, and overall survival were 62.6%, 39.1%, and 59.1%, respectively. Overall survival was significantly better in group 3 (p=0.002). In multivariate analyses, cT3 was the most powerful adverse factor affecting clinical outcomes. Incidence and severity of radiation pneumonitis were not different among groups, while no patients developed grade 2 esophagitis in group 3 (p=0.003). Under current Korean Health Insurance Policy, RT cost per person was 22.5% less in group 3 compared with others. CONCLUSION: The current study demonstrated that 60 Gy in 15 fractions instead of 60 Gy in 20 fractions resulted in comparable clinical outcomes with excellent safety, direct cost saving, and improved convenience to the patients with tumors located at ≥ 1.5 cm from the esophagus.
Appointments and Schedules* ; Carcinoma, Non-Small-Cell Lung* ; Cost Savings ; Disease-Free Survival ; Dose Fractionation ; Esophagitis ; Esophagus ; Follow-Up Studies ; Humans ; Incidence ; Insurance, Health ; Multivariate Analysis ; Radiation Pneumonitis ; Radiotherapy

OBJECTIVE: To compare the dosimetric differences of dosiology between intensity-modulated arc radiotherapy (IMAT) and dynamic intensity-modulated radiation therapy (dIMRT) in nasopharyngeal carcinoma. METHODS: CT data from 25 patients treated in our radiotherapy center were selected randomly for this study. For each patient, the IMAT technique and the fixed beam dIMRT technique were accomplished by the simultaneously integrated boost. Dose volume histogram (DVH) data, isodose distribution, monitor units (MUs) and treatment time were compared in the two techniques. RESULTS: There was no significant difference between the IMAT and the dIMRT in dose received by 95% of target volumes (D(95)) (P>0.05). Overall, the mean dose (D(mean)), maximal dose (D(max)) and volume percentage receiving at least of 107% of the prescribed dose (V(107%)) of planning target volume (PTV) for the IMAT were increased slightly ,compared with the dlMRT (P<0.05). There were no significant differences in dosimetric indices of organs at risk (OARs) including spinal cord,optical nerves,lens and temporomandibular joints in the two techniques (P>0.05). Compared with the dlMRI, the D(max) of brain stem for the IMAT was increased slightly (P<0.05). Similar trends was observed for the D(mean) and dose received by 50% of volume (D(50)) of the left and right parotid glands (P<0.05). Healthy tissue (defined as the volume of the body minus PTV,B-P) irradiated from 800 cGy in the IMAT was higher, and that from 1200-4500 cGy was lower compared with the dlMRI (P<0.05).The average number of MUs was reduced by 62.7% per fraction, and the treatment time was on average reduced by 60.1% per fraction in the IMAT compared with the dlMRI. CONCLUSION There is a slight difference in dosiology between the two radiotherapy techniques investigated, but they both meet the clinical requirement. Compared with the dIMRT, the IMAT delivers less irradiation to healthy tissue, uses fewer MUs and takes less time during radiotherapy for nasopharyngeal carcinoma.
Carcinoma, Squamous Cell ; radiotherapy ; Dose Fractionation, Radiation ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Radiometry ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; methods ; Radiotherapy, Intensity-Modulated ; methods

OBJECTIVETo evaluate the radiation induced parotid dysfunction in nasopharyngeal carcinoma (NPC) patients who had received different methods of radiotherapy.

METHODSFrom January 1996 to January 2000, 380 NPC patients were divided into conventional fraction (CF-175 patients), late-course accelerated hyperfractionation (LCAF-63 patients) and intensity modulated radiation therapy (IMRT-142 patients) groups. Conventional radiotherapy was given with a total dose of 70 Gy. Patients in the LCAF group were treated with the same fractionation as CF group until the dose of 36 - 40 Gy, then followed by LCAF radiotherapy to a total dose of 75 Gy. IMRT in the form of full-course was given to a total dose of 72 Gy. Acute parotiditis was observed during the treatment. The parotid secretory function was examined 2 years after radiotherapy.

RESULTSThe dose of parotid in IMRT was much lower than those in the other 2 groups. Extreme damage rates of parotid secretory function in CF, LCAF and IMRT groups were 81.7%, 81.0% and 69.7% (P < 0.05); acute parotiditis rates were 23.4%, 20.4% and 41.3% respectively, with the differences among the 3 groups significant (P < 0.05).

CONCLUSIONThe radiation parotid functional damage differs in the various methods of radiotherapy. IMRT, being able to improve the tumor target coverage and spare the adjacent critical structures, is indicated for NPC.

Adolescent ; Adult ; Carcinoma, Squamous Cell ; radiotherapy ; Dose Fractionation ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Parotid Gland ; physiopathology ; radiation effects ; Parotitis ; etiology ; Radiation Injuries ; physiopathology ; Radiotherapy, Intensity-Modulated ; methods

BACKGROUNDRadiotherapy plays a critical role in the management of non-small cell lung cancer (NSCLC). This study was conducted to identify gene expression profiles of acquired radioresistant NSCLC cell line established by fractionated ionizing radiation (FIR) by cDNA microarray.

METHODSThe human lung adenocarcinoma cell line Anip973 was treated with high energy X-ray to receive 60 Gy in 4 Gy fractions. The radiosensitivity of Anip973R and its parental line were measured by clonogenic assay. Gene expression profiles of Anip973R and its parental line were analyzed using cDNA microarray consisting of 21 522 human genes. Identified partly different expressive genes were validated by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR).

RESULTSFifty-nine upregulated and 43 downregulated genes were identified to radio-resistant Anip973R. Up-regulated genes were associated with DNA damage repair (DDB2), extracellular matrix (LOX), cell adhesion (CDH2), and apoptosis (CRYAB). Down-regulated genes were associated with angiogenesis (GBP-1), immune response (CD83), and calcium signaling pathway (TNNC1). Subsequent validation of selected eleven genes (CD24, DDB2, IGFBP3, LOX, CDH2, CRYAB, PROCR, ANXA1 DCN, GBP-1 and CD83) by Q-RT-PCR was consistent with microarray analysis.

CONCLUSIONSFractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.

Adenocarcinoma ; genetics ; radiotherapy ; Carcinoma, Non-Small-Cell Lung ; genetics ; radiotherapy ; Cell Line, Tumor ; radiation effects ; Dose Fractionation ; Dose-Response Relationship, Radiation ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; genetics ; radiotherapy ; Oligonucleotide Array Sequence Analysis ; Radiation Tolerance ; Reverse Transcriptase Polymerase Chain Reaction

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity> or =grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV(5Gy)-rV(35Gy): normal liver volume receiving or =grade 2 occurred in 10 patients (13%): grade 2 in 9 patients and grade 3 in 1 patient. On univariate analysis, baseline Child-Pugh (CP) score (5 vs. 6-8), normal liver volume, and planning target volume were the significant clinical predictors. All dosimetric parameters were significant: rV(20Gy) was the most significant predictor. On multivariate analysis, baseline CP score (hazard ratio, 0.026; P=0.001) was the only significant predictor. In conclusion, SABR using 3 fractions in primary and metastatic liver cancers produces low hepatic toxicity, especially in patients with a baseline CP score of 5. However, further studies are needed to minimize hepatic toxicity in patients with baseline CP scores> or =6.
Aged ; *Dose Fractionation ; Female ; Hepatitis/*etiology/pathology/prevention & control ; Humans ; Liver Neoplasms/complications/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Metastasis ; Radiation Injuries/*etiology/pathology/prevention & control ; Radiosurgery/*adverse effects/*methods ; Radiotherapy Dosage ; Treatment Outcome

BACKGROUND AND OBJECTIVEMany patterns of treatment have been used to treat esophageal carcinoma in the past years, however, an optimal treatment is still the key issue to be explored. Therefore, we analyzed the published literature about radiotherapy for esophageal cancer in recent 15 years in China, and observed the survival rate, local control rate, adverse events, and so on.

METHODSA total of 56 eligible papers about radiotherapy for esophageal squamous cell carcinoma published in Chinese core periodicals between 1994 and 2009 were selected. The survival rates, local control rates, and adverse events were analyzed.

RESULTSThe 1-, 2-, 3-, and 5-year overall survival rates of the patients reported in the 56 papers were (67.99 ± 12.55)%, (49.59 ± 11.79)%, (34.50 ± 11.49)%, and (23.31 ± 10.21)%, respectively. The 1-, 2-, 3-, and 5-year local control rates were (73.04 ± 13.37)%, (61.60 ± 15.50)%, (51.77 ± 15.00)%, and (50.15 ± 21.36)%, respectively. The acute esophageal toxicity rate was (44.84 ± 25.71)% in 32 papers reported in recent 15 years, and the acute esophageal toxicity over grade II accounted for (35.93 ± 22.90)%. The rates of acute esophageal toxicity were (26.84 ± 13.12)% for conventional radiation, (53.72 ± 21.82)% for late course accelerated hyperfractionation radiation, (61.33 ± 28.69)% for concurrent chemoradiotherapy, and (40.31 ± 27.22)% for other ways of radiation. The late toxicity rate described in 23 papers was (5.13 ± 4.07)% in recent 15 years. The late toxicity rates were (5.66 ± 3.42)% for conventional radiation, (4.53± 4.07)% for late course accelerated hyperfractionation radiation, (2.24±1.31)% for concurrent chemoradiotherapy, and (7.34 ± 5.06)% for other ways of radiation. The Meta analysis indicated that concurrent chemoradiotherapy was better than late course accelerated hyperfractionation radiation and conventional radiation.

CONCLUSIONSThe long-term survival of patients with esophageal cancer is still disappointed in recent years. Concurrent chemoradiotherapy shows advantages in treating esophageal cancer and, currently, is the best non-surgical treatment of esophageal cancer.

Carcinoma, Squamous Cell ; drug therapy ; radiotherapy ; Chemoradiotherapy ; adverse effects ; methods ; China ; Dose Fractionation ; Esophageal Neoplasms ; drug therapy ; radiotherapy ; Esophagitis ; etiology ; Humans ; Radiation Injuries ; etiology ; Radiotherapy ; adverse effects ; methods ; Survival Rate

OBJECTIVETo evaluate the efficacy of late accelerated hyperfractionated conformal radiotherapy (LACF) combined with capecitabine on esophageal carcinoma.

METHODSOne hundred and sixty eight patients of esophageal cancer were randomly divided into 3 groups, including the radiotherapy alone group (CF) which received conventional conformal radiotherapy to a total of 60 - 66 Gy, LCAF group which received conventional fractionated conformal radiotherapy during the first two-thirds of the treatment to a dose about 40 Gy/20F/4W, then followed by late accelerated hyperfractionated conformal radiotherapy, twice daily radiotherapy at 1.3 Gy per fraction to a total dose about 64 - 69 Gy, and LCAF + C group (late accelerated hyperfractionated radiotherapy combined with capecitabine), in which patients were treated as the same as the LCAF group, except that they were treated with capecitabine (1.5 g po bid) from beginning of the radiotherapy to the end.

RESULTSThe short-term results of the 3 groups were 74.0%, 85.5% and 95.2%, respectively (P = 0.006). The local control rates at 1, 3 and 5 years were 64.0%, 30.0%, 24.0% in the CF group, 81.8%, 65.5%, 58.2% in the LCAF group and 90.1%, 77.8%, 74.6% in the LCAF+C group, respectively. The 1-, 3- and 5-year survival rates of the 3 groups were 58.0%, 20.0%, 8.0%; 78.2%, 36.4%, 17.0% and 85.7%, 55.6%, 30.2%, respectively. The effect of LCAF+C group was better than that of LCAF group and CF group. The incidence of acute tracheitis and acute esophagitis in the LCAF+C group and LCAF group was higher than that in the CF group, but there was no stastistically significant difference between the 2 groups. There was no statistically significant difference in distant metastasis in the 3 groups.

CONCLUSIONSCapecitabine, as an effective chemosensitizater combined with late accelerate hyperfractionated radiotherapy can improve the short-term results of treatment of esophageal cancer. The value of this combined treatment in distant metastasis reqires further study in the clinic.

Antimetabolites, Antineoplastic ; therapeutic use ; Capecitabine ; Carcinoma, Squamous Cell ; mortality ; pathology ; therapy ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Dose Fractionation ; Esophageal Neoplasms ; mortality ; pathology ; therapy ; Esophagitis ; etiology ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; adverse effects ; methods ; Remission Induction ; Survival Rate

OBJECTIVETo examine the effect of fractioned ionizing radiation on the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and multidrug resistance (MDR1) in human esophageal cancer cells.

METHODSThe mRNA and protein levels of HIF-1alpha and MDR1 in esophageal caner EC9706 cells incubated in the presence of 150 micromol/L CoCl(2) were measured before and after the irradiation by quantitative RT-PCR and Western blotting, respectively. The chemosensitivity and radiosensitivity of the cells were analyzed by MTT assay and clone formation assay.

RESULTSMDR1 and HIF1alpha expressions were significantly up-regulated in the cells following hypoxia or irradiation (P<0.05). The surviving cell fraction in the exclusive irradiation group was significantly lower than that irradiation+hypoxia group (P<0.05). Compared with exclusive hypoxia group, MDR1 and HIF1alpha expressions were decreased significantly in irradiation+hypoxia group (P<0.05). HIF1alpha expression showed a positive correlation to MDR1 expression (P<0.01).

CONCLUSIONHypoxia is an important factor to induce resistance to chemo- and radiotherapy. Low-dose fractioned irradiation can lower MDR1 and HIF1alpha expressions in esophageal cancer cells, which should be considered when combining radiotherapy chemotherapy for esophageal cancer patients.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; Cell Line, Tumor ; Dose Fractionation ; Esophageal Neoplasms ; pathology ; radiotherapy ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Radiation, Ionizing