Jiade Jay Lu

Patients’ preference for radiotherapy fractionation schedule in the palliation of symptomatic unresectable lung cancer†

The palliative radiotherapeutic management of unresectable non‐small‐cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient’s choice of Fx schedule after involvement in a decision‐making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision‐making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients’ preferences. Of 92 patients enrolled, 55% chose the longer schedule. English‐speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2–7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision‐making process. The decision board was useful in aiding decision‐making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients’ preferences, there were significant alterations of preferred schedules because of RO’s own biases.

Tailoring distant metastatic imaging for patients with clinically localized undifferentiated nasopharyngeal carcinoma

PURPOSE The 2000 practice guidelines of the National Comprehensive Cancer Network recommend World Health Organization Type 2-3 nasopharyngeal carcinoma (NPC) be staged for distant disease using chest X-ray and bone scan. Our aim was to evaluate these modalities plus liver ultrasonography for American Joint Committee on Cancer/International Union Against Cancer 1997 clinical Stage I-IVB NPC. METHODS AND MATERIALS Between February 1999 and May 2002, all patients with clinical (examination plus CT/MRI of head and neck) Stage I-IVB undifferentiated NPC were prospectively evaluated for distant disease with chest X-ray, liver ultrasonography, and bone scan. Suspicious lesions underwent confirmatory investigation, and patients were reevaluated at 4 months. RESULTS In the 139 patients evaluated, the positive yield was 3.6% and prevalence was 5.8% (0.7% lung, 2.2% skeletal, and 2.9% liver metastases). The prevalence increased by N stage (p = 0.004) and overall stage (p = 0.05). Compared with N3 disease (odds ratio 1.0), the odds of metastases for N0, N1, and N2 disease was 0, 0.12, and 0.33, respectively. The positive yield was 0%, 1.8%, 4.8%, and 14.3% for N0, N1, N2, and N3 disease, respectively. CONCLUSION This is the first study to evaluate the use of distant staging investigations for American Joint Committee on Cancer/International Union Against Cancer 1997 staged NPC. We recommend alterations to the 2000 National Comprehensive Cancer Network guidelines as follows: high-risk (N3) disease should be fully staged with chest X-ray, bone scan, and liver ultrasonography; intermediate risk (N1 and N2) disease may be staged using all three modalities on an institutional basis. No evidence supports distant imaging for low-risk (N0 or Stage I) disease.

Clinical outcome of palliative radiotherapy for locally advanced symptomatic gastric cancer in the modern era.

AbstractThe purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques.We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity.Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (⩽39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (&agr;/&bgr; ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia).External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (⩽39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing.

An ultrasonographic evaluation of skin thickness in breast cancer patients after postmastectomy radiation therapy

BackgroundTo determine the usefulness of ultrasonography in the assessment of post radiotherapy skin changes in postmastectomy breast cancer patients.MethodsPatients treated for postmastectomy radiotherapy in National University Hospital (NUH) and Tan Tock Seng Hospital (TTSH), Singapore between January 2004- December 2005 was recruited retrospectively. Ultrasound scan was performed on these Asian patients who had been treated to a total dose of 46-50 Gy with 1 cm bolus placed on the skin. The ultrasound scans were performed blinded to the RTOG scores, and the skin thickness of the individually marked points on the irradiated chest wall was compared to the corresponding points on the non-irradiated breast.ResultsThe mean total skin thickness inclusive of the epidermis and the dermis of the right irradiated chest wall was 0.1712 mm (± 0.03392 mm) compared with the contra-lateral non-irradiated breast which was 0.1845 mm (± 0.04089 mm; p = 0.007). The left irradiated chest wall had a mean skin thickness of 0.1764 mm (± 0.03184 mm) compared with the right non-irradiated breast which was 0.1835 mm (± 0.02584 mm; p = 0.025). These independent t-tests produced a significant difference of reduced skin thickness on the right irradiated chest wall, p = 0.007 (p < 0.05) and left irradiated chest wall p = 0.025 (p < 0.025) in comparison to the non-irradiated skin thickness investigating chronic skin reactions. Patients with grade 2 acute skin toxicity presented with thinner skin as compared to patients with grade 1 (p = 0.006).ConclusionsThis study has shown that there is a statistically significant difference between the skin thicknesses of the irradiated chest wall and the contra-lateral non-irradiated breast and a predisposition to chronic reactions was found in patients with acute RTOG scoring of grade1 and grade 2.

Role of Computed Tomography Imaging in Predicting Response of Nasopharyngeal Carcinoma to Definitive Radiation Therapy

Purpose: The purpose of this study was to investigate the role of posttreatment computed tomography (CT) scans in assessing response of nasopharyngeal carcinoma (NPC) to definitive radiotherapy.

Development of a spreadsheet for the calculation of new tools to improve the reporting of the results of medical research

Primary objective. Confidence levels, clinical significance curves and risk – benefit contours have recently been developed with the aim of improving the interpretation of clinical studies. It has been suggested that their use may complement traditional methods of result reporting (i.e. p values and 95% confidence intervals), and subsequently improve medical decision-making. These new methods have been used to report study results; however, widespread use may be hampered by the lack of available computer software. Our objective was to design user-friendly software to enable researchers to use these statistical methods. Research design. A spreadsheet was designed to calculate these statistics for the assessment of two arm medical studies. The spreadsheet was tested using a wide range of input data and operating systems. User-friendliness was tested by researchers who had no background in statistics. Main outcomes and results. The confidence calculator was successfully designed, and found to be user-friendly. The spreadsheet is MS Excel-based to allow wide usage. The spreadsheet is freely available from the author and from the web site http://www.primercollaboration.com/Tools/tools.html. Conclusions. We have successfully designed a spreadsheet that is simple to use and freely accessible for researchers. This is the first such software that calculates confidence levels, clinical significance curves, and risk – benefit contours.

Prospective Phase II Trial of Concomitant Boost Radiotherapy For Stage II Nasopharyngeal Carcinoma: An Evaluation of Response and Toxicity

Introduction: Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results in loco‐regional control of around 80%. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost (C‐Boost) schedule.

Influence of the Way Results Are Presented on Research Interpretation and Medical Decision Making: The PRIMER Collaboration Randomized Studies:

Background. The manner of presentation of research results may affect how clinicians interpret research and make clinical decisions. The authors evaluate whether the use of confidence levels improve research interpretation and decision making compared with P values and 95% confidence intervals. Methods. The 2 Presentation and Interpretation of Medical Research (PRIMER) studies were 3-arm randomized trials. PRIMER 1 presented results of 5 fictitious scenarios with P values (P), P plus 95% confidence intervals (P + CI), or P, CI, and confidence levels (P + CI + CL); PRIMER 2 compared P + CI + CL, P + CI, and P + CL. Clinicians were asked to identify the correct interpretation of scenarios in terms of statistical and clinical significance and then indicate the intended decision making in terms of treatment recommendation. Results. Seventy-five and 246 clinicians participated in PRIMER 1 and PRIMER 2, respectively. In PRIMER 1, P+CI+CL was superior to P + CI and P (P < 0.05); the latter 2 arms did not differ significantly. Decision making was not significantly different between arms. In PRIMER 2, P+CI+CL resulted in better interpretation than P + CI (P = 0.03), with no difference between P + CI and P + CL. In combined analysis, the odds of correct interpretation were higher for P+CI+CL than P+CI (odds ratio = 1.73, P=0.005, 95% CI= 1.19--2.52). Decision making was better for P + CI+ CL (P = 0.03). On multivariate analysis, the P + CI+ CL arm and clinicians with statistics training, not in private practice, or participating in PRIMER 1 had better interpretation. The P + CI+ CL arm was the only factor improving decision making. Conclusions. Presenting research with a combination of P values, confidence intervals, and confidence levels leads to better interpretation and decision making by clinicians.