Negligible or weak expression of cyclooxygenase-2 is associated with poorer outcome in endemic nasopharyngeal carcinoma: analysis of data from randomized trial between radiation alone versus concurrent chemo-radiation (SQNP-01)

Background:
Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.
Methods:
58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.
Results:
58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.
Conclusions:
Contrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients.

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Implications of a high-definition multileaf collimator (HD-MLC) on treatment planning techniques for stereotactic body radiation therapy (SBRT): a planning study

PurposeTo assess the impact of two multileaf collimator (MLC) systems (2.5 and 5 mm leaf widths) on three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and dynamic conformal arc techniques for stereotactic body radiation therapy (SBRT) of liver and lung lesions.
Methods:
Twenty-nine SBRT plans of primary liver (n=11) and lung (n=18) tumors were the basis of this study. Five-millimeter leaf width 120-leaf Varian Millennium (M120) MLC-based plans served as reference, and were designed using static conformal beams (3DCRT), sliding-window intensity-modulated beams (IMRT), or dynamic conformal arcs (DCA). Reference plans were either re-optimized or recomputed, with identical planning parameters, for a 2.5-mm width 120-leaf BrainLAB/Varian high-definition (HD120) MLC system. Dose computation was based on the anisotropic analytical algorithm (AAA, Varian Medical Systems) with tissue heterogeneity taken into account. Each plan was normalized such that 100% of the prescription dose covered 95% of the planning target volume (PTV). Isodose distributions and dose-volume histograms (DVHs) were computed and plans were evaluated with respect to target coverage criteria, normal tissue sparing criteria, as well as treatment efficiency.
Results:
Dosimetric differences achieved using M120 and the HD120 MLC planning were generally small. Dose conformality improved in 51.7%, 62.1% and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. Dose heterogeneity increased in 75.9%, 51.7%, and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. DVH curves demonstrated a decreased volume of normal tissue irradiated to the lower (90%, 50% and 25%) isodose levels with the HD120 MLC.
Conclusions:
Data derived from the present comparative assessment suggest dosimetric merit of the high definition MLC system over the millennium MLC system. However, the clinical significance of these results warrants further investigation in order to determine whether the observed dosimetric advantages translate into outcome improvements.

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Radiation-induced cancer after radiotherapy for non-Hodgkin’s lymphoma of the head and neck: a retrospective study

Background:
Survivors of non-Hodgkin’s lymphoma (NHL) are well known to be at an increased risk of second malignancies. In this study, we evaluated the incidence and clinical features of head and neck cancer (HNC) occurring after radiotherapy (RT) for NHL.Material and methodsWe investigated the clinical records of 322 patients who had received RT for early-stage NHL of the head and neck at our institute between 1952 and 2000.
Results:
There were 4 patients with a second HNC developing in the irradiated field, consisting of 2 patients with gum cancer, 1 case with tongue cancer and 1 case with maxillary sinus cancer. The pathological diagnosis in all the 4 patients was squamous cell carcinoma (SCC). Two of the patients (one with gum cancer and one with maxillary sinus cancer) died of the second HNC, while the remaining 2 patients are still living at the time of writing after therapy for the second HNC, with neither recurrence of the second tumor nor relapse of the primary tumor. The ratio of the observed to the expected number (O/E ratio) of a second HNC was calculated to be 12.7 (95%CI, 4.07-35.0), and the absolute excess risk (AER) per 10,000 person-years was 13.3. The median interval between the RT and the diagnosis of the second HNC was 17.0 years (range, 8.7 to 22.7years).Conlusions: The risk of HNC significantly increased after RT for early-stage NHL. These results suggest that second HNC can be regarded as one of the late complications of RT for NHL of the head and neck.

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Extraneural metastases from cranial meningioma: a case report

Extracranial metastases from brain meningiomas is a rare, but well-documented entity. Metastases occur mostly in the lungs, pleura and liver, but may also affect lymph nodes and bones. We report here on a patient who was treated for an atypical brain meningioma with multiple surgeries and multiple sessions of stereotactic radiosurgery with good control of his brain disease. Thirteen years after diagnosis, he developed bilateral large sacroiliac and abdominal metastases.

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Clinical outcome of breast cancer occurring after treatment for Hodgkin’s lymphoma: case-control analysis

Background:
To evaluate diagnosis, management and outcome of breast cancer (BC) occurring after irradiation for Hodgkin’s lymphoma (HL).
Methods:
39 cases of BC in 28 HL survivors were retrospectively reviewed. 21 patients were included in a case-control analysis.
Results:
The median age at diagnosis of HL and BC was 25.3 and 45.3 years, respectively. The median interval to develop BC was 16.1 years. Eleven women (39.2%) had bilateral disease. Mode of detection of the index breast cancers was by mammographic screening in 17 patients (60.7%), palpable lump in 8 patients (28.6%), clinical examination in two patients (7.1%), and unknown in one patient (3.6%). Case-control analysis showed that histological features and prognosis of BC after HL were similar to those of primary BC, however, for BC after HL, mastectomy was the predominant surgery (P = 0.001) and adjuvant radiotherapy and anthracycline-based chemotherapy were less frequently used as compared to primary BC (P < 0.001 and 0.003, respectively).
Conclusions:
The previous history of HL does not appear to be a poor prognostic factor for BC occurring thereafter.

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Monte Carlo dose verification of prostate patients treated with simultaneous integrated boost intensity modulated radiation therapy

Background:
To evaluate the dosimetric differences between Superposition/Convolution (SC) and Monte Carlo (MC) calculated dose distributions for simultaneous integrated boost (SIB) prostate cancer intensity modulated radiotherapy (IMRT) compared to experimental (film) measurements and the implications for clinical treatments.
Methods:
Twenty-two prostate patients treated with an in-house SIB-IMRT protocol were selected. SC-based plans used for treatment were re-evaluated with EGS4-based MC calculations for treatment verification. Accuracy was evaluated with-respect-to film-based dosimetry. Comparisons used gamma (gamma)-index, distance-to-agreement (DTA), and superimposed dose distributions. The treatment plans were also compared based on dose-volume indices and 3-D gamma index for targets and critical structures.
Results:
Flat-phantom comparisons demonstrated that the MC algorithm predicted measurements better than the SC algorithm. The average PTVprostate D98 agreement between SC and MC was 1.2% +/- 1.1. For rectum, the average differences in SC and MC calculated D50 ranged from -3.6% to 3.4%. For small bowel, there were up to 30.2% +/- 40.7 (range: 0.2%, 115%) differences between SC and MC calculated average D50 index. For femurs, the differences in average D50 reached up to 8.6% +/- 3.6 (range: 1.2%, 14.5%). For PTVprostate and PTVnodes, the average gamma scores were >95.0%.
Conclusion:
MC agrees better with film measurements than SC. Although, on average, SC-calculated doses agreed with MC calculations within the targets within 2%, there were deviations up to 5% for some patient’s treatment plans. For some patients, the magnitude of such deviations might decrease the intended target dose levels that are required for the treatment protocol, placing the patients in different dose levels that do not satisfy the protocol dose requirements.

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Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (http://www.ncbi.nlm.nih.gov/geo/). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results.

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Radiotherapy quality assurance review in a multi-center randomized trial of limited-disease small cell lung cancer: the Japan Clinical Oncology Group (JCOG) trial 0202

Background:
The purpose of this study was to analyze the radiotherapy (RT) quality assurance (QA) assessment in Japan Clinical Oncology Group (JCOG) 0202, which was the first trial that required on-going RT QA review in the JCOG.
Methods:
JCOG 0202 was a multi-center phase III trial comparing two types of consolidation chemotherapy after concurrent chemoradiotherapy for limited-disease small cell lung cancer. RT requirements included a total dose of 45 Gy / 30 fx (bis in die, BID / twice a day) without heterogeneity correction; elective nodal irradiation (ENI) of 30 Gy; at least 1 cm margin around the clinical target volume (CTV); and interfraction interval of 6 hours or longer. Dose constraints were defined in regards to the spinal cord and the lung. The QA assessment was classed as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable (I/NE).
Results:
A total of 283 cases were accrued, of which 204 were fully evaluable, excluding 79 I/NE cases. There were 18 VU in gross tumor volume (GTV) coverage (8% of 238 evaluated); 4 VU and 23 DA in elective nodal irradiation (ENI) (2% and 9% of 243 evaluated, respectively). Some VU were observed in organs at risk (1 VU in the lung and 5 VU in the spinal cord). Overall RT compliance (PP + DA) was 92% (187 of 204 fully evaluable). Comparison between the former and latter halves of the accrued cases revealed that the number of VU and DA had decreased.
Conclusions:
The results of the RT QA assessment in JCOG 0202 seemed to be acceptable, providing reliable results.

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Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

Background:
In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system.
Methods:
Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days.
Results:
By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients.
Conclusions:
Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.

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Comparison of rectal volume definition techniques and their influence on rectal toxicity in patients with prostate cancer treated with 3D conformal radiotherapy: a dose-volume analysis

Background:
To evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT).
Methods:
Clinical and dosimetric data were evaluated for 94 patients who received a total dose 3DCRT of 70 Gy, and rectal doses were compared in four different rectal contouring techniques: the prostate-containing CT sections (method 1); 1 cm above and below the planning target volume (PTV) (method 2); 110 mm starting from the anal verge (method 3); and from the anal verge to the sigmoid flexure (method 4). The percentage of rectal volume receiving RT doses (30-70 Gy) and minimum, mean rectal doses were assessed.
Results:
Median age was 69 years. Percentage of rectal volume receiving high doses (>70 Gy) were higher with the techniques that contoured smaller rectal volumes. In methods 2 and 3, the percentage of rectal volume receiving > 70 Gy was significantly higher in patients with than without rectal bleeding (method 2: 30.8% vs. 22.5%, respectively (p = 0.03); method 3: 26.9% vs. 18.1%, respectively (p = 0.006)). Mean rectal dose was significant predictor of rectal bleeding only in method 3 (48.8 Gy in patients with bleeding vs. 44.4 Gy in patients without bleeding; p = 0.02).
Conclusions:
Different techniques of rectal contouring significantly influence the calculation of radiation doses to the rectum and the prediction of rectal toxicity. Rectal volume receiving higher doses (>70 Gy) and mean rectal doses may significantly predict rectal bleeding for techniques contouring larger rectal volumes, as was in method 3.

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