Comparison of Multiple Treatment Planning Techniques for High-Grade Glioma Tumors Near to Critical Organs.

AIM: The purpose of this study was to compare 6 treatment planning methods (5-beam coplanar intensity-modulated radiotherapy (IMRT), 7-beam coplanar IMRT, 7-beam noncoplanar IMRT, 2 full arc coplanar volumetric modulated arc therapy (VMAT), 2 half partial arc coplanar VMAT, and 2 half partial arc noncoplanar VMAT) for high-grade gliomas with planning target volumes (PTVs) overlapping the optic pathway and/or brainstem. PATIENTS AND METHODS: 27 previously-treated patients with high-grade gliomas were replanned for treatment with IMRT5, IMRT7, IMRT7-non, VMAT2f, VMAT2h, and VMAT2h-non. In order to perform a comparative study of the treatment outcomes, 3 tumor localizations (right-sided, left-sided, and central tumors) were selected. Patients were administered a PTV dose of 60 Gy in 30 fractions with a maximum permitted dose of 110%. RESULTS: Comparison of the 3 IMRT plans and 3 VMAT plans was performed for all 27 patients. The median conformity index was significantly higher (p < 0.05) in all IMRT plans compared to all VMAT plans in the case of right sided tumors. Significant differences were also observed between coplanar and noncoplanar plans in IMRT and VMAT in right-sided tumors (p < 0.05). Differences in brainstem mean doses were only found to be significant between coplanar and noncoplanar plans in centrally-located tumors. In right- and left-sided tumors, the VMAT2f plans demonstrated higher values than all IMRT plans in their mean values for radiation doses to the ipsilateral optic nerves, contralateral optic nerves, ipsilateral lens, ipsilateral eye, contralateral lens, contralateral eye, and contralateral optic nerves, as well in the maximums for the optic chiasm and contralateral optic nerves. Significantly faster treatment times were achieved with all VMAT plans compared to IMRT plans. CONCLUSION: IMRT techniques provided better target coverage than VMAT plans. However, VMAT techniques reduced treatment delivery time more than IMRT techniques. Technique selection for tumors located in 3 different localizations should be individualized in accordance with patients' specific parameters.

Re-Irradiation of Locoregional NSCLC Recurrence Using Robotic Stereotactic Body Radiotherapy.

BACKGROUND: We evaluated the efficacy, toxicity, and dose responses of re-irradiation with stereotactic body radiotherapy (SBRT) in patients with recurrent non- small cell lung cancer (NSCLC) after previous irradiation. PATIENTS AND METHODS: 28 patients were included. Previous median radiation doses were 54 and 66 Gy. The median interval time between previous radiotherapy and SBRT was 14 months. The median follow-up time after SBRT was 9 months (range 3-93 months). To evaluate the effectiveness of SBRT, local control, overall survival, and treatment-related toxicity were reported. RESULTS: SBRT doses and fractionation ranged from 60 to 30 Gy and from 3 to 8, respectively, according to previous doses, location of the recurrence, and interval time. 65% of tumor recurrences overlapped with previous treatment, while 35% of tumors recurred outside of the previous treatment. 4 patients had local progression after SBRT at their first follow-up. The Kaplan-Meier estimates of the 1- and 2-year actuarial overall survival were 71 and 42%, respectively. The mean survival following SBRT was 32.8 months, and the median survival was 21 months. No grade 3 or higher toxicities were observed. CONCLUSION: Robotic SBRT is a tolerable treatment option with manageable toxicity which can be used with radical or palliative intent in carefully selected patients with locally recurrent tumors after previous irradiation.

Intravascular Placement of Metallic Coils as Lung Tumor Markers for CyberKnife Stereotactic Radiation Therapy.

OBJECTIVE: To present our experience with placing endovascular coils in pulmonary arteries used as a fiducial marker for CyberKnife therapy and to describe the technical details and complications of the procedure. MATERIALS AND METHODS: Between June 2005 and September 2013, 163 patients with primary or secondary lung malignancies, referred for fiducial placement for stereotactic radiosurgery, were retrospectively reviewed. Fourteen patients (9 men, 5 women; mean age, 70 years) with a history of pneumonectomy (n = 3), lobectomy (n = 3) or with severe cardiopulmonary co-morbidity (n = 8) underwent coil (fiducial marker) placement. Pushable or detachable platinum micro coils (n = 49) 2-3 mm in size were inserted through coaxial microcatheters into a small distal pulmonary artery in the vicinity of the tumor under biplane angiography/fluoroscopy guidance. RESULTS: Forty nine coils with a median number of 3 coils per tumor were placed with a mean tumor-coil distance of 2.7 cm. Forty three (87.7%) of 49 coils were successfully used as fiducial markers. Two coils could not be used due to a larger tumor-coil distance (> 50 mm). Four coils were in an acceptable position but their non-coiling shape precluded tumor tracking for CyberKnife treatment. No major complications needing further medication other than nominal therapy, hospitalization more than one night or permanent adverse sequale were observed. CONCLUSION: Endovascular placement of coil as a fiducial marker is safe and feasible during CyberKnife therapy, and might be an option for the patients in which percutaneous transthoracic fiducial placement might be risky.

Tumor-Cut: segmentation of brain tumors on contrast enhanced MR images for radiosurgery applications.

In this paper, we present a fast and robust practical tool for segmentation of solid tumors with minimal user interaction to assist clinicians and researchers in radiosurgery planning and assessment of the response to the therapy. Particularly, a cellular automata (CA) based seeded tumor segmentation method on contrast enhanced T1 weighted magnetic resonance (MR) images, which standardizes the volume of interest (VOI) and seed selection, is proposed. First, we establish the connection of the CA-based segmentation to the graph-theoretic methods to show that the iterative CA framework solves the shortest path problem. In that regard, we modify the state transition function of the CA to calculate the exact shortest path solution. Furthermore, a sensitivity parameter is introduced to adapt to the heterogeneous tumor segmentation problem, and an implicit level set surface is evolved on a tumor probability map constructed from CA states to impose spatial smoothness. Sufficient information to initialize the algorithm is gathered from the user simply by a line drawn on the maximum diameter of the tumor, in line with the clinical practice. Furthermore, an algorithm based on CA is presented to differentiate necrotic and enhancing tumor tissue content, which gains importance for a detailed assessment of radiation therapy response. Validation studies on both clinical and synthetic brain tumor datasets demonstrate 80%-90% overlap performance of the proposed algorithm with an emphasis on less sensitivity to seed initialization, robustness with respect to different and heterogeneous tumor types, and its efficiency in terms of computation time.

Comparison of dose distributions and organs at risk (OAR) doses in conventional tangential technique (CTT) and IMRT plans with different numbers of beam in left-sided breast cancer.

AIM: Our aim was to improve dose distribution to the left breast and to determine the dose received by the ipsilateral lung, heart, contralateral lung and contralateral breast during primary left-sided breast irradiation by using intensity modulated radiotherapy (IMRT) techniques compared to conventional tangential techniques (CTT). At the same time, different beams of IMRT plans were compared to each other in respect to CI, HI and organs at risk (OAR) dose. BACKGROUND: Conventional early breast cancer treatment consists of lumpectomy followed by whole breast radiation therapy. CTT is a traditional method used for whole breast radiotherapy and includes standard wedged tangents (two opposed wedged tangential photon beams). The IMRT technique has been widely used for many treatment sites, allowing both improved sparing of normal tissues and more conformal dose distributions. IMRT is a new technique for whole breast radiotherapy. IMRT is used to improve conformity and homogeneity and used to reduce OAR doses. MATERIALS AND METHODS: Thirty patients with left-sided breast carcinoma were treated between 2005 and 2008 using 6, 18 or mixed 6/18 MV photons for primary breast irradiation following breast conserving surgery (BCS). The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, ipsilateral lung, contralateral lung and heart tissues as organs at risk (OAR). IMRT with seven beams (IMRT7), nine beams (IMRT9) and 11 beams (IMRT11) plans were developed and compared with CTT and among each other. The conformity index (CI), homogeneity index (HI), and doses to OAR were compared to each other. RESULTS: ALL OF IMRT PLANS SIGNIFICANTLY IMPROVED CI (CTT: 0.76; IMRT7: 0.84; IMRT9: 0.84; IMRT11: 0.85), HI (CTT: 1.16; IMRT7: 1.12; IMRT9: 1.11; IMRT11: 1.11), volume of the ipsilateral lung receiving more than 20 Gy (>V20 Gy) (CTT: 14.6; IMRT7: 9.08; IMRT9: 8.10; IMRT11: 8.60), and volume of the heart receiving more than 30 Gy (>V30 Gy) (CTT: 6.7; IMRT7: 4.04; IMRT9: 2.80; IMRT11: 2.98) compared to CTT. All IMRT plans were found to significantly decrease >V20 Gy and >V30 Gy volumes compared to conformal plans. But IMRT plans increased the volume of OAR receiving low dose radiotherapy: volume of contralateral lung receiving 5 and 10 Gy (CTT: 0.0-0.0; IMRT7: 19.0-0.7; IMRT9: 17.2-0.66; IMRT11: 18.7-0.58, respectively) and volume of contralateral breast receiving 10 Gy (CTT: 0.03; IMRT7: 0.38; IMRT9: 0.60; IMRT11: 0.68). The differences among IMRT plans with increased number of beams were not statistically significant. CONCLUSION: IMRT significantly improved conformity and homogeneity index for plans. Heart and lung volumes receiving high doses were decreased, but OAR receiving low doses was increased.

Cellular automata segmentation of brain tumors on post contrast MR images.

In this paper, we re-examine the cellular automata (CA) algorithm to show that the result of its state evolution converges to that of the shortest path algorithm. We proposed a complete tumor segmentation method on post contrast T1 MR images, which standardizes the VOI and seed selection, uses CA transition rules adapted to the problem and evolves a level set surface on CA states to impose spatial smoothness. Validation studies on 13 clinical and 5 synthetic brain tumors demonstrated the proposed algorithm outperforms graph cut and grow cut algorithms in all cases with a lower sensitivity to initialization and tumor type.

Dosimetric and physical comparison of IMRT and CyberKnife plans in the treatment of localized prostate cancer.

AIM: The aim of our study was the dosimetric and physical evaluation of the CK and IMRT treatment plans for 16 patients with localized prostate cancer. BACKGROUND: Intensity modulated radiation therapy (IMRT) is one of the recent technical advances in radiotherapy. The prostate is a well suited site to be treated with IMRT. The challenge of accurately delivering the IMRT needs to be supported by new advances such as image-guidance and four-dimensional computed conformal radiation therapy (4DCRT) tomography. CyberKnife (CK) provides real time orthogonal X-ray imaging of the patient during treatment course to follow gold fiducials installed into the prostate and to achieve motion correlation between online acquired X-ray imaging and digital reconstructed radiographs (DRRs) which are obtained from planning computed tomography images by translating and rotating the treatment table in five directions. METHODS AND MATERIALS: Sixteen IMRT and CK plans were performed to be compared in terms of conformity (CI), heterogeneity indices (HI), percentage doses of 100% (V100), 66% (V66), 50% (V50), 33% (V33) and 10% (V10) volumes of the bladder and rectum. Dose-volume histograms for target and critical organs, (CI) and indices (HI) and isodose lines were analyzed to evaluate the treatment plans. RESULTS: Statistically significant differences in the percentage rectal doses delivered to V10, V33, and V50 of the rectum were detected in favor of the CK plans (p values; <0.001, <0.001 and 0.019, respectively). The percentage doses for V66 and V100 of the rectum were larger in CK plans (13%, 2% in IMRT and 21%, 3% in CK plans, respectively). Percentage bladder doses for V10 and V33 were significantly lower in CK plans [96% in IMRT vs 48% in CK (p < 0.001) and 34% in IMRT vs 24% in CK (p = 0.047)]. Lower percentage doses were observed for V50, V66 of the bladder for the IMRT. They were 5.4% and 3.45% for IMRT and 13.4% and 8.05% for CK, respectively. Median CI of planning target volume (PTV) for IMRT and CK plans were 0.94 and 1.23, respectively (p < 0.001). CONCLUSION: Both systems have a very good ability to create highly conformal volumetric dose distributions. Median HI of PTV for IMRT and CK plans were 1.08 and 1.33, respectively (p < 0.001).

Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study.

INTRODUCTION: In this prospective study, the efficacy and safety of radiotherapy combined with zoledronic acid was evaluated. MATERIALS AND METHODS: Breast cancer patients with painful bone metastases were randomized to either high- or reduced-dose radiotherapy. All patients received zoledronic acid (4 mg) every 28 days from the beginning of radiotherapy. Analgesic and pain scores in addition to visual analog score (VAS) for treatment satisfaction and whole-body bone scintigraphy were evaluated. RESULTS AND CONCLUSION: No significant differences could be found in analgesic or pain scores and bone scintigraphy results between the groups. Our results suggest that reduced-dose radiotherapy produces similar response rates and response durations when used concomitantly with zoledronic acid.

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.

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.

Evaluation of infections in non-small cell lung cancer patients treated with radiotherapy.

PURPOSE: We aim to determine infections occurring in patients with non-small cell lung cancer during radiotherapy (RT). METHODS AND MATERIALS: A total of 181 patients had been treated with thoracic radiotherapy between October 1995 and December 1999. Radiotherapy was given using 1.8-3Gray (Gy) fraction daily, five fractions a week for a total dose of 59.4Gy (30-70.2Gy). A complete history was collected retrospectively for each patient. All microbiological examinations were performed according to the routine procedures of the hospital laboratory. Numeric and categoric variables were employed such as sex, age, performance status, histology, stage, chemotherapy, usage of corticosteroids, neutropenia, surgery, hospitalization, associated diseases, smoking during treatment, package per year of cigarette smoking, dose of radiotherapy, and response rates. RESULTS: Infections developed in 84 patients (46%, 84/181) during thoracic radiotherapy. A 101 episodes of infections developed in these patients. Most patients suffered from sputum production (65%), cough (59%), auscultation findings (31%) and fever (31%). Gram-negative bacteria were the most frequently isolated pathogens in the cultures of specimens (70%, 16/23 samples). Neoadjuvant chemotherapy (OR=4.81; 95% CI, 1.57-9.12; p=0.003) and neutropenia (OR=4.25; 95% CI, 1.44-6.89; p=0.009) were found as risk factors for influencing infection based on logistic regression analyses. Package per year of cigarette smoking was found statistically significantly higher in patients with infections than patients without infections (p=0.001). A slight increase in infections, which was of borderline statistical significance (p=0.07), was observed in patients age over 70. Ciprofloxacin and clarithromycin were the most frequently used agents in treatment. Median survival was 9 months in the patients with infection and 13 months in the 97 patients without infection. Overall survival seemed to be statistically significantly better in patients without infection than patients with infection (p=0.042) calculated using Kaplan-Meier method. Based on Cox regression analyses; overall survival was not correlated to presence of infection but associated with poor performance status (5940 cGy (OR=2.06; 95% CI, 0.72-7.18; p=0.007) and the absence of response to treatment (OR=2.45; 95% CI, 0.89-14.23; p<0.001) were also found to be risk factors for survival. CONCLUSIONS: Infections are important causes of morbidity and mortality in lung cancer patients. The control of infection in these patients may improve the survival. Predisposing factors and treatment management approaches in non-small cell lung cancer should be defined carefully.

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.