Evaluation of late effects of postoperative radiotherapy in patients with medulloblastoma.

We aimed to evaluate long-term toxicity in children with medulloblastoma treated with postoperative radiotherapy (RT). This study included 21 patients aged 4-16 who had been diagnosed with medulloblastoma. All of the patients in the study received postoperative craniospinal RT. Postoperative RT followed by chemotherapy was the treatment protocol. A total of 13 patients (62%) received chemotherapy concurrently with RT. Overall survival was 50 months (range, 1-169 months) and disease-free survival was 39 months (range, 4-171 months). In the data analysis, the heights of 11 patients (91.6%) were found to be below 50% on the height curve, and 8 (66.6%) patients had weights below 50% on the weight curve. Mean sitting height was 72.58 ± 6.33 cm, and this was statistically correlated with parameters such as LH level (p=0.037), testosterone level (p=0.020), height (p=0.002), weight (p=0.033) and age at diagnosis (p=0.002). Radiation therapy for medulloblastoma seems to have a late toxic effect on long-term survivors. With the improving survival rate of medulloblastoma patients, RT doses should be as low as possible without sacrificing efficacy.

Effects of EGFR, CK19, CK20 and Survinin gene expression on radiotherapy results in patients with locally advanced head and neck cancer.

PURPOSE: To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). MATERIALS AND METHODS: Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the ΔΔCt method. The same process was repeated for peripheral blood samples taken after RT (AR). RESULTS: The female/male ratio was 3:23 and the mean age was 56.5 years (38-75 years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). CONCLUSIONS: In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.

[Our results of postoperative radiation therapy in patients with salivary gland cancer]. / Tükürük bezi kanserli olgularda ameliyat sonrasi radyoterapi sonuçlarimiz.

OBJECTIVES: This study aims to evaluate our single center experience in patients with a salivary gland tumor receiving postoperative radiation therapy (RT). PATIENTS AND METHODS: Between January 1996 and December 2011, the records of 34 salivary gland tumor patients who were operated and referred to our clinic for adjuvant RT were retrospectively analyzed. Radiation therapy was applied to the primary tumor and lymphatics at a median dose of 60 Gy (54 to 60 Gy) with 1.8-2 Gy/fraction. RESULTS: The median follow-up was 38 months (range, 3 to 204 months). The most common site of involvement was the parotid gland in 21 patients (62%), followed by the submandibular gland in 11 patients (%24) and minor salivary gland in two patients (9%). Five-year overall survival (OS) was 49% (range, 3 to 206 months) and disease free survival (DFS) was 61% (range, 1 to 173 months). Six patients had local or regional recurrences (18%), while 13 patients (38%) had distant metastasis. A tumor size larger than 4 cm, over six weeks referral time to RT, and existence of metastatic lymph node were found to be poor prognostic factors for OS (p=0.023, p=0.039, respectively), and DFS (p=0.046). While extracapsular involvement significantly reduced the DFS and OS (p=0.022, p=0.050, respectively), overall RT time affected DFS alone (p=0.046). CONCLUSION: We recommend adjuvant RT in high-risk patients operated due to a salivary gland tumor.

Radio-protective effect of cinnamic acid, a phenolic phytochemical, on genomic instability induced by X-rays in human blood lymphocytes in vitro.

The present study was designed to determine the protective activity of cinnamic acid against induction by X-rays of genomic instability in normal human blood lymphocytes. This radio-protective activity was assessed by use of the cytokinesis-block micronucleus test and the alkaline comet assay, with human blood lymphocytes isolated from two healthy donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for the irradiation with 1 or 2 Gy. Treatment of the lymphocytes with cinnamic acid prior to irradiation reduced the number of micronuclei when compared with that in control samples. Treatment with cinnamic acid without irradiation did not increase the number of micronuclei and did not show a cytostatic effect in the lymphocytes. The results of the alkaline comet assay revealed that cinnamic acid reduces the DNA damage induced by X-rays, showing a significant radio-protective effect. Cinnamic acid decreased the frequency of irradiation-induced micronuclei by 16-55% and reduced DNA breakage by 17-50%, as determined by the alkaline comet assay. Cinnamic acid may thus act as a radio-protective compound, and future studies may focus on elucidating the mechanism by which cinnamic acid offers radioprotection.

Role of PET/CT in treatment planning for head and neck cancer patients undergoing definitive radiotherapy.

BACKGROUND: In this study, we aimed to investigate the benefits of 18F-deoxyglucose positron emission tomography/computed tomography (FGD-PET/CT) imaging for staging and radiotherapy planning in patients with head and neck cancer undergoing definitive radiotherapy. MATERIALS AND METHODS: Thirty-seven head and neck cancer patients who had undergone definitive radiotherapy and PET/CT at the Uludag University Medical Faculty Department of Radiation Oncology were investigated in order to determine the role of PET/CT in staging and radiotherapy planning. RESULTS: The median age of this patient group of 32 males and 5 females was 57 years (13-84years). The stage remained the same in 18 cases, decreased in 5 cases and increased in 14 cases with PET/CT imaging. Total gross tumor volume (GTV) determined by CT (GTVCT-Total) was increased in 32 cases (86.5%) when compared to total GTV determined by PET/CT (GTVPET/CT-Total). The GTV of the primary tumor determined by PET/CT (GTVPET/CT) was larger in 3 cases and smaller in 34 cases compared to that determined by CT (GTVCT). The GTV of lymph nodes determined by PET/CT (GTVLNPET/CT) was larger in 20 cases (54%) and smaller in 12 cases (32.5%) when compared to GTV values determined by CT (GTVLNCT). No pathological lymph nodes were observed in the remaining five cases with both CT and PET/ CT. CONCLUSIONS: We can conclude that PET/CT can significantly affect both pretreatment staging and assessed target tumor volume in patients with head and neck cancer. We therefore recommend examining such cases with PEC/CT before treatment.

An evaluation of the results of chemoradiotherapy and surgical treatment for hypopharyngeal cancer.

OBJECTIVES: This study aims to evaluate the efficacy chemoradiotherapy and surgical treatment in patients with hypopharyngeal cancer. PATIENTS AND METHODS: Between January 2003 and July 2009, 48 patients (31 males, 17 females; mean age 55.5±13.4 years; range 29 to 84 years) who were diagnosed with hypopharyngeal cancer were retrospectively evaluated. The patients were assigned into surgery (n=17) and chemoradiotherapy (n=31) groups. RESULTS: The overall survival of the patients with advanced disease in the surgery group was statistically higher than those in the chemoradiotherapy group. The recurrence rate of the patients was 35.3% in the surgery group, whereas it was 41.4% in the chemoradiotherapy group. CONCLUSION: Our study results indicated that the survival rates were higher in the surgery group. On the other hand, chemoradiotherapy had the advantage of laryngeal preservation.

The evaluation of bcl-2 expression as a prognostic marker in early stage laryngeal cancer.

AIMS AND BACKGROUND: To evaluate the effect of bcl-2 expression on the local control and overall survival of patients with early stage laryngeal cancer treated with radiotherapy alone. METHODS AND STUDY DESIGN: We included 53 patients with stage Tis, T1, and T2 laryngeal cancer who were irradiated in our department. Paraffin blocks of all biopsy specimens were subjected to immunohistochemical analysis with a bcl-2 oncoprotein mouse clone 124 Scytek kit. RESULTS: The mean follow-up time was 61 months (range, 7-166). Local-regional recurrence was observed in 10 (19%) patients. Forty-three patients (81%) had negative bcl-2 staining, 5 patients (9%) had + staining, 3 patients (6%) ++ staining, and 2 patients (4%) +++ staining. No relationship was detected between bcl-2 expression and local control or overall survival. The emergence of a recurrence and a younger age (<50 years) were significantly related to poor overall survival (P = 0.000 and P = 0.021, respectively). Patients with hemoglobin levels in the middle of radiotherapy and at the end of radiotherapy higher than 13 g/dl had improved overall survival in multivariate analyses (P = 0.002 and P = 0.001, respectively). Regarding local control, the following were poor prognostic factors: smoking more than 20 cigarettes a day (P = 0.001) and being younger than 50 years of age (P = 0.001). CONCLUSIONS: No correlation was observed between bcl-2 expression and local control or overall survival. Whereas hemoglobin level, age and existence of a recurrence had a prognostic impact on overall survival, patient age and smoking status influenced local control rates.

Radioprotection by two phenolic compounds: chlorogenic and quinic acid, on X-ray induced DNA damage in human blood lymphocytes in vitro.

The present study was designed to determine the radioprotective effect of two phytochemicals, namely, quinic acid and chlorogenic acid, against X-ray irradiation-induced genomic instability in non-tumorigenic human blood lymphocytes. The protective ability of two phenolic acids against radiation-induced DNA damage was assessed using the alkaline comet assay in human blood lymphocytes isolated from two healthy human donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for irradiation. The results of the alkaline comet assay revealed that quinic acid and chlorogenic acid decreased the DNA damage induced by X-ray irradiation and provided a significant radioprotective effect. Quinic acid decreased the presence of irradiation-induced DNA damage by 5.99-53.57% and chlorogenic acid by 4.49-48.15%, as determined by the alkaline comet assay. The results show that quinic acid and chlorogenic acid may act as radioprotective compounds. Future studies should focus on determining the mechanism by which these phenolic acids provide radioprotection.

Thyroid functions in long-term survivors of pediatric Hodgkin's lymphoma treated with chemotherapy and radiotherapy.

OBJECTIVE: Post-treatment endocrine disturbances are common in cancer patients who have received radiotherapy or chemotherapy. The objective of this study was to evaluate the thyroid functions of long-term survivors of pediatric Hodgkin's lymphoma treated with chemotherapy and radiotherapy. METHODS: Thyroid functions of 55 Hodgkin's lymphoma patients (M/F:2.05/1) in complete remission were evaluated retrospectively. RESULTS: The mean age of the patients at diagnosis was 10.35±4.09 (range: 2.83-17) years and the mean follow-up period was 5.54±3.68 (range: 0.92-13.92) years. All patients received chemotherapy; a total of 50 patients (90.9%) underwent radiotherapy, 42 (76.4%) of whom received neck/mantle radiotherapy. Thyroid function tests were abnormal in 14 (24.5%) patients and normal - in the remaining 41 (74.5%). A diagnosis of subclinical and overt hypothyroidism was made in 11 (78.6%) and 3 (21.4%) patients with abnormal thyroid function tests, respectively. Nearly one-fourth (21.4%) of all thyroid function disorders were detected in the first year of follow-up. A statistically significant correlation was found between the dose of mantle radiotherapy and thyroid function disorder (p=0.002). In addition, statistically significant correlations were established between thyroid examination or thyroid ultrasonography findings and thyroid functions (p <0.001 or p=0.006, respectively). CONCLUSIONS: Radiation-induced thyroid disorders may develop in pediatric Hodgkin's lymphoma patients in complete remission starting as early as the first year after treatment and are dose-dependent. Patients, particularly those who have been exposed to radiotherapy of the neck, must be followed up closely for occurrence of thyroid dysfunctions.

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer.

BACKGROUND/AIMS: 5-Fluorouracil-based chemoradiotherapy is the most widely used treatment modality in the adjuvant treatment of rectal cancer. Capecitabine represents a valuable alternative to 5-Fluorouracil in this situation. METHODOLOGY: Patients with stage II and stage III rectal adenocarcinoma, who were included in this analysis, received adjuvant chemoradiotherapy consisting of external-beam radiotherapy (50.4-54Gy) either with 5-Fluorouracil at a median dose of 300 mg/m2/day by protracted venous infusion for 5 days a week, or capecitabine at a median dose of 1650 mg/m2/day for 5 days a week after surgery. The data concerning the toxicity and the efficacy of the treatments were compared in patients treated with 5-Fluorouracil- and capecitabine-based chemoradiotherapy. RESULTS: Forty-three patients received 5-Fluorouracil, and 24 patients received capecitabine during adjuvant radiotherapy. Although there were no differences between the groups in terms of toxicity rates, distant metastasis-free survival, disease-free survival, and overall survival rates; a trend for improved loco-regional recurrence-free survival rate was observed in the capecitabine arm (p = 0.063). CONCLUSIONS: Capecitabine is at least as effective as 5-Fluorouracil in the postoperative treatment of rectal adenocarcinoma. Considering the trend for improved loco-regional recurrence-free survival rate in the capecitabine arm, it seems that the drug exerts better synergy with radiotherapy in this situation.

Carcinoma originating from aberrant breast tissue. A case report and review of the literature.

Carcinoma arising from ectopic breast tissue, either supernumerary breast or aberrant breast tissue, is extremely rare. Carcinoma occurs more frequently in the ectopic breast tissue of the axilla than in extra-axillary ectopic breast tissue. Here we report a case of an invasive lobular carcinoma arising from extra-axillary ectopic breast tissue and presenting as a subcutaneous nodule.

Patterns of care for lung cancer in radiation oncology departments of Turkey.

PURPOSE: To determine the patterns of care for lung cancer in Turkish radiation oncology centers. METHODS AND MATERIALS: Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. RESULTS: The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were ">/= IB" disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIA unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. CONCLUSION: There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach.

Factors influencing axillary node metastasis in breast cancer.

AIMS AND BACKGROUND: The status of the axillary lymph nodes at the time of diagnosis has been accepted as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. The aim of our study was to determine which factors influence axillary node involvement in invasive breast cancer. METHODS: The data presented here were obtained from 344 patients who were treated for invasive breast cancer at the Department of Radiation Oncology, Uludag University Medical College, Bursa, Turkey. Possible prognostic factors were categorized as patient related and tumor related. The Mann-Whitney U test was used for univariate analysis and logistic regression was used for multivariate analysis. RESULTS: In univariate analysis, a familial cancer history (P = 0.0042), age < 40 years (P = 0.0276), higher T stage (P < 0.0000), nipple involvement (P = 0.0345), skin involvement (P = 0.0270), perineural invasion (P = 0.0231), and lymphatic vessel invasion (P < 0.0000) were correlated with increased axillary node involvement. A higher incidence of > or = 4 involved lymph nodes was associated with higher T stage (P = 0.0004), nipple involvement (P = 0.0292), presence of an extensive intraductal component (P = 0.0023), skin involvement (P = 0.0008), perineural invasion (P = 0.0523), and lymphatic vessel invasion (P < 0.0000) in univariate analysis. In multivariate analysis, age < 40 years (P = 0.0454), cancer history within the family (P = 0.0024), higher T stage (P = 0.0339), lymphatic vessel invasion (P = 0.0003), and perineural invasion (P = 0.0408) were found to be independent factors for axillary lymph node positivity. Age < 40 years (P = 0.0221), perineural invasion (P = 0.0408), and an extensive intraductal component (P = 0.0132) were associated with an increased incidence of > or = 4 involved nodes in the logistic regression analysis. In patients with breast cancer, the incidence of axillary lymph node involvement was independently influenced by age < 40 years, presence of cancer history within the family, higher T stage, lymphatic vessel invasion, and perineural invasion. CONCLUSIONS: In conclusion, absence of familial cancer history, presence of lymphatic vessel invasion, higher T stage, and age below 40 years independently increased the risk of axillary node involvement. Presence of perineural invasion and lymphatic vessel invasion, age below 40, and an extensive intraductal component of more than 25% independently affected the risk of having > or = 4 nodes involved. Patients characterized by these factors may be classified into a higher risk group for nodal involvement, but more data are needed to define factors that can help in the decision-making regarding the omission of axillary treatment.

Synchronous breast cancer in spouses.

Breast cancer in both spouses is extremely rare. There are 7 metachronous cases and 1 synchronous case in the English literature. No case has been reported in which 1 of the spouses had bilateral breast cancer. In this paper, we report a synchronous pair of cases where 1 of the spouses (wife) had bilateral breast cancer and the other (husband) had breast cancer.

Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer.

AIMS AND BACKGROUND: To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. RESULTS: After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). CONCLUSIONS: The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incorporation of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

Postoperative concomitant chemoradiotherapy in locally advanced rectal cancer.

BACKGROUND/AIMS: To gain maximal effectiveness while decreasing toxicity by giving 5-fluorouracil for 45 minutes starting just within 5 minutes after the completion of radiotherapy thrice weekly. METHODOLOGY: Thirty-eight patients with locally advanced rectal cancer were enrolled in the study. Ranges of total radiation doses were between 50.4 Gy and 61.2 Gy with a median of 59.4 Gy with fraction size of 1.8 Gy five times weekly. 5-fluorouracil was administered thrice weekly with the dose of 250-300mg/m2/day concomitantly with radiation therapy. RESULTS: Median follow-up time was 30 months. Administration of chemotherapy concomitant with radiotherapy (p=0.089), AJCC stage III (p=0.079), Duke's stage C (p=0.079), presence of lymph node involvement (p=0.079) and presence of local recurrence (p=0.066) appeared to be effecting distant metastasis although differences did not reach statistically significance. Mean overall survival was 46 months in patients without any distant metastasis (SD: 3.28; 95% CI: 39.46 and 52.31) while it was 35 months in patients with distant metastasis (SD: 5.71; 95% CI: 23.52 and 45.90, p=0.016). CONCLUSIONS: Our results have provided further evidence of the ability of postoperative chemoradiotherapy to delay and prevent local recurrence and metastasis of rectal cancer.

Preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

BACKGROUND/AIMS: To determine the percentage of responders and the resectability rate for patients with locally advanced carcinoma of the rectum treated by infusional 5-fluorouracil chemotherapy and pelvic radiation. METHODOLOGY: Twenty-four patients with a diagnosis of locally advanced unresectable rectal cancer received preoperative 5-fluorouracil by intravenous infusion at the dose of 250-300mg/m2/day concurrent with pelvic radiation (median 50.4 Gy/28 fractions). Surgery was performed with a mean delay of 15 days after completion of irradiation and included 11 abdominoperineal resections and five anal sphincter-preserving procedures. RESULTS: The median follow-up was 22 months. Complete histological response occurred in 6%, and tumor down-staging in 58% of cases. There was a significant difference in the rate of local control based on the distance of the tumor from the anal verge (>5.4cm; p=0.046). Our results have suggested the importance of the total dose on the local control (p=0.061). Higher local failure rate has been observed with prolonged treatment time (p=0.018). With metastasis-free survival as the endpoint, only stage (p=0.027) was a statistically significant prognostic factor. CONCLUSIONS: The favorable influence of higher doses of preoperative radiotherapy on pathologic stage has been observed. Even after preoperative radiotherapy, postoperative staging remained a prognostic factor.

Successful salvage therapy of resistant gestational trophoblastic disease with etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP).

A 26-year-old woman who had been treated for nonmetastatic gestational trophoblastic tumor with three courses of methotrexate with folinic acid rescue and had been lost to follow up for 4 years was referred with the fractional curettage diagnosis of choriocarcinoma that had been performed for abnormal vaginal bleeding. Her serum beta human chorionic gonadotropin (betahCG) was 706000 mIU/mL and there were multiple pulmonary metastatic foci. The uterus was 12 weeks pregnant-size and a 6 x 6-cm tumor mass was seen within the anterior uterine wall at ultrasonography. Following total abdominal hysterectomy etoposide, methotrexate, actinomycin-D, vincristine and cyclophosphamide (EMA/CO) regimen was given. Whole brain radiation of 30 Gy in 3 weeks for brain metastasis, discovered in magnetic resonance imaging was given after the first course. Since serum betahCG levels plateaued after three courses of chemotherapy and multiple pulmonary metastases persisted, treatment was shifted to etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP) regimen. She was in remission after three courses of chemotherapy.

Investigation of genotoxic effect of taxol plus radiation on mice bone marrow cells.

In this study, we investigated the genotoxic effect of taxol, radiation, or taxol plus radiation on highly proliferative normal tissue-bone marrow cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered bolus intravenously through the tail vein. Radiation was given by using a linear accelerator. There were four treatment categories, which had a total of 34 groups. Each group consisted of five animals. The first was the control category that had one group (n = 5). The second treatment category was taxol alone, which had three groups as per taxol dose alone (n = 15). The third treatment category was radiation alone, which had three groups as per the radiation dose (n = 15). The fourth treatment category was taxol plus radiation, which had 27 groups as per combined radiation dose plus taxol dose concentration and as per pre-treatment timing sequence of taxol before radiation (n = 135). Mice were sacrificed 24 h after taxol or radiation or combined administration using ether anesthesia. The cells were then dropped on two labeled slides, flamed, air dried, and stained in 7% Giemsa; 20-30 well-spread mitotic metaphases were analyzed for each animal; the cells with chromosome breaks, acentric fragments, and rearrangements were evaluated on x1,000 magnification with light microscope (Zeiss axioplan). The mitotic index was determined by counting the number of mitotic cells among 1,000 cells per animal. Differences between groups were evaluated with Student's t-test statistically. Taxol caused a dose-dependent increase in chromosomal aberrations (P = 0.027). Similarly, radiation caused a dose-dependent increase in chromosomal aberrations (P = 0.003) and decreased mitotic index (P = 0.002). In combination, there were a small enhancements at the 40 mg/kg taxol dose level and at 0.25 and 0.5 Gy radiation doses in the 48 h group. However, an increase in chromosomal aberrations was observed after 48 hours of taxol exposure when compared 12 or 24 h of taxol exposure (P = 0.001 and P = 0.019). These findings suggest that taxol at the high doses with low dose radiation caused radiosensitizing effect in bone marrow cells. Forty-eight-hour pretreatment of taxol exposure followed by radiation caused significant induction of chromosomal aberrations and a reduction of mitotic index when compared to other taxol timing sequence.