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)

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Prostate specific antigen bounce after intensity-modulated radiation therapy in an Asian population

AbstractObjectiveSerum prostate specific antigen (PSA) is commonly used to evaluate treatment response after definitive radiation therapy (RT). However, PSA levels can temporarily rise without a clear reason, termed “PSA bounce”, and often engender great anxiety for both patients and physicians. The present study aimed to determine the prevalence and factors that predict “PSA bounce” after intensity-modulated radiation therapy (IMRT), and the relevance to biochemical failure and cancer recurrence in an Asian population.MethodsWe retrospectively reviewed 206 patients who received IMRT for prostate cancer from 2004 to 2012 in the National Cancer Centre Singapore. These patients were followed up with regular PSA monitoring. We defined “PSA bounce” as a rise of 0.1 ng/mL, followed by two consecutive falls. Patients with biochemical failure (PSA nadir + 2 ng/mL) were further evaluated for cancer recurrence.ResultsSixty-one patients (29.6%) experienced “PSA bounce”, at a median time of 16 months and lasted for 12 months. Age remained the most consistent predictor of the incidence, duration and extent of “PSA bounce”. Other contributory factors included baseline PSA, Gleason score and PSA nadir. Hormonal therapy and prostate volume did not affect this phenomenon. Sixteen patients (7.8%) developed biochemical recurrence, at median time of 32 months, of which 11 were confirmed to have metastatic disease. The median follow-up time was 71 months.ConclusionA younger age predicts PSA bounce incidence, duration and magnitude. The extent of bounce appears to be lower in Asian population. The interval to occurrence and extent of PSA elevation separates PSA bounce from disease recurrence

Treatment of nasopharyngeal carcinoma using intensity-modulated radiotherapy - the national cancer centre Singapore experience

Purpose: The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating nasopharyngeal carcinoma (NPC) patients with intensity-modulated radiotherapy (IMRT). Methods and materials: A review was conducted on case records of 195 patients with histologically proven, nonmetastatic NPC treated with IMRT between 2002 and 2005. MRI of the head and neck was fused with CT simulation images. All plans had target volumes at three dose levels, with a prescribed dose of 70 Gy to the gross disease, in 2.0–2.12 Gy/fraction over 33–35 fractions. Cisplatin-based chemotherapy was offered to Stage III/IV patients. Results: Median patient age was 52 years, and 69% were male. Median follow-up was 36.5 months. One hundred and twenty-three patients had Stage III/IV disease (63%); 50 (26%) had T4 disease. One hundred and eighty-eight (96%) had complete response; 7 (4%) had partial response. Of the complete responders, 10 (5.3%) had local recurrence, giving a 3-year local recurrence-free survival estimate of 93.1% and a 3-year disease-free survival of 82.1%. Fifty-one patients (26%) had at least one Grade 3 toxicity. Conclusions: Results from our series are comparable to those reported by other centers. Acute toxicity is common. Local failure or persistent disease, especially in patients with bulky T4 disease, are issues that must be addressed in future trials

An assessment of the magnitude of intra-fraction movement of head-and-neck IMRT cases and its implication on the action-level of the imaging protocol.

BACKGROUND AND PURPOSE: A planning margin ⩽3mm is employed in some head-and-neck IMRT cases due to the proximity of critical structures. This study aims to explore the need to redefine the action-level in the head-and-neck imaging protocol in consideration of the intra-fraction movement. MATERIAL AND METHODS: This is a local study of 18 patients treated using the same immobilisation system and setup protocol. Post-treatment orthogonal pair of kilovoltage X-ray images was acquired on the first three days of treatment. 106 sets of pre- and post-treatment kV X-ray images acquired over 53 fractions were analysed against the treatment planning DRR for calculation of intra-fraction movement. RESULTS: Individual mean intra-fraction movement in all directions ranged from -1.8 to 1.1mm. Population mean (median) intra-fraction movement in the x-, y-, and z-planes were -0.1mm (0mm), -0.3mm (-0.3mm) and -0.2mm (-0.2mm) respectively. Intra-fraction movement in all three dimensions, x-, y- and z-planes were considered statistically significant (p<0.05). 7 out of 53 fractions (13.2%) were highlighted as the combined magnitude of the intra-fraction motion with the uncorrected pre-treatment setup errors had exceeded the boundaries of given margins. CONCLUSIONS: 3mm-AL was not adequate to account for intra-fraction movement when the CTV-PTV margin was ⩽3mm and should be excluded from the routine imaging protocol and daily image-guided radiotherapy should be employed. Adjusting the action-level to 2mm would allow a more confident approach in delivery of the prescribed dose in head-and-neck IMRT cases

Evaluation of inter- and intra-observer variations in prostate gland delineation using CT-alone versus CT/TPUS

Background: This study aims to explore the role of four-dimensional (4D) transperineal ultrasound (TPUS) in the contouring of prostate gland with planning computed tomography (CT) images, in the absence of magnetic resonance imaging (MRI). Materials and methods: Five radiation oncologists (ROs) performed two rounds of prostate gland contouring (single-blinded) on CT-alone and CT/TPUS datasets obtained from 10 patients who underwent TPUS-guided external beam radiotherapy. Parameters include prostate volume, DICE similarity coefficient (DSC) and centroid position. Wilcoxon signed-rank test assessed the significance of inter-modality differences, and the intraclass correlation coefficient (ICC) reflected inter- and intra-observer reliability of parameters. Results: Inter-modality analysis revealed high agreement (based on DSC and centroid position) of prostate gland contours between CT-alone and CT/TPUS. Statistical significant difference was observed in the superior-inferior direction of the prostate centroid position (p = 0.011). All modalities yielded excellent inter-observer reliability of delineated prostate volume with ICC &gt; 0.9, mean DSC &gt; 0.8 and centroid position: CT-alone (ICC = 1.000) and CT/TPUS (ICC = 0.999) left-right (L/R); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 0.998) anterior-posterior (A/P); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 1.000) superior-inferior (S/I). Similarly, all modalities yielded excellent intra-observer reliability of delineated prostate volume, ICC &gt; 0.9 and mean DSC &gt; 0.8. Lastly, intra-observer reliability was excellent on both imaging modalities for the prostate centroid position, ICC &gt; 0.9. Conclusion: TPUS does not add significantly to the amount of anatomical information provided by CT images. However, TPUS can supplement planning CT to achieve a higher positional accuracy in the S/I direction if access to CT/MRI fusion is limited

Intra-patient and inter-patient comparisons of DNA damage response biomarkers in Nasopharynx Cancer (NPC): analysis of NCC0901 randomised controlled trial of induction chemotherapy in locally advanced NPC

Abstract Background Inter-patient heterogeneity in radiation-induced DNA damage responses is proposed to reflect intrinsic variations in tumour and normal tissue radiation sensitivity, but the prediction of phenotype by a molecular biomarker is influenced by clinical confounders and assay reproducibility. Here, we characterised the intrapatient and inter-patient heterogeneity in biomarkers of DNA damage and repair and radiation-induced apoptosis. Methods We enrolled 85 of 172 patients with locally advanced nasopharynx cancer from a randomised controlled phase II/III trial of induction chemotherapy added to chemo-radiotherapy. G0 blood lymphocytes were harvested from these patients, and irradiated with 1, 4, and 8 Gy ex vivo. DNA damage induction (1 Gy 0.5 h) and repair (4 Gy 24 h) were assessed by duplicate γH2AX foci assays in 50–100 cells. Duplicate FLICA assays performed at 48 h post-8 Gy were employed as surrogate of radiation-induced apoptosis; %FLICA-positive cells were quantified by flow cytometry. Results We observed limited intrapatient variation in γH2AX foci and %FLICA readouts; median difference of duplicate foci scores was − 0.37 (IQR = − 1.256-0.800) for 1 Gy 0.5 h and 0.09 (IQR = − 0.685-0.792) for 4 Gy 24 h; ICC of ≥0.80 was observed for duplicate %FLICA0Gy and %FLICA8Gy assays of CD4+ and CD8+ T lymphocytes. As expected, we observed wide inter-patient heterogeneity in both assays that was independent of intrapatient variation and clinical covariates, with the exception of age, which was inversely correlated with %FLICAbackground-corrected (Spearman R = − 0.406, P < 0.001 [CD4+]; R = − 0.220, P = 0.04 [CD8+]). Lastly, an exploratory case-control analysis indicates increased levels of γH2AX foci at 4 Gy 24 h in patients with severe late radiotherapy-induced xerostomia (P = 0.05). Conclusion Here, we confirmed the technical reproducibility of DNA damage response assays for clinical implementation as biomarkers of clinical radiosensitivity in nasopharynx cancer patients