Rahul Mukherjee - Academia.edu (original) (raw)

Papers by Rahul Mukherjee

Research paper thumbnail of External Audit of Clinical Practice and Medical Decision-Making in a New Asian Oncology Center: Results and Implications for Both Developing and Developed Nations

International Journal of Radiation Oncology Biology Physics, 2005

Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic f... more Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic factors, including marital/live-in status. Married or men with a live-in partner treated on 3 RTOG head and neck clinical trials had improved local control and overall survival compared to single men while this effect difference did not translate to women. RTOG 97-14 compared 30 Gy in 10 fractions to 8 Gy in 1 fraction in the treatment of patients with symptomatic bone metastases from breast and prostate cancer. The specific aim of this study is to evaluate outcome differences based upon marital status. Materials/Methods: RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Comparisons of re-treatment rates and overall survival were made based upon gender, marital status and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate the time to re-treatment at 36 months and Grays test was used to test for treatment differences within the same groupings. Survival differences were evaluated by means of the log rank test. Marital status, gender, KPS and treatment were variables tested in a univariate Cox model evaluating the time to re-treatment. Results: Women and men receiving 30 Gy had a significantly longer time to re-treatment compared to patients receiving 8 Gy, pϽ0.0001 and pϽ0.026 respectively. Women lived significantly longer than men, regardless of treatment arm (median survival of females and males is 11.8 and 7.8 months, respectively, pϽ0.0001). Married men and women and single women receiving 30 Gy had significantly longer time to re-treatment, pϭ0.007, pϭ0.0052, and pϭ0.0009 respectively. We failed to show a difference in re-treatment rates in single men receiving either 30 Gy or 8 Gy. Re-treatment rates were higher in married and single women receiving 8 Gy regardless of KPS while only men with initial KPS of 70 -80 had fewer re-treatments from 30 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive re-treatment, pϽ0.0001, with a trend towards single patients not receiving re-treatment, pϭ0.07. Conclusions: Non-disease related variables, like social support, might influence the results of clinical trials with subjective end-points such as re-treatment rates. The lower re-treatment rates observed in single male patients receiving 8 Gy may be a result of the lack of adequate social support systems in place to facilitate additional care. Clinicians may need to be sensitive to the greater likelihood of negative outcomes in single male patients but more focused strategies depend on better specification of what aspects of being single are most disadvantageous to men with cancer.

Research paper thumbnail of A Study of Complications Arising From Different Methods of Anesthesia Used in High-Dose-Rate Brachytherapy for Cervical Cancer

American Journal of Clinical Oncology-cancer Clinical Trials, 2004

The purpose of this report is to review the complications related to different methods of anesthe... more The purpose of this report is to review the complications related to different methods of anesthesia for high-dose-rate (HDR) brachytherapy for cervical carcinoma. All patients diagnosed with cervical cancer between 1999 and 2002 treated with 3-channel HDR brachytherapy were entered. Complications due to anesthesia for each fraction of brachytherapy were graded using the Common Toxicity Criteria. Eighty-four fractions of brachytherapy were delivered to 18 patients: 19 fractions with patients under general anesthesia (GA), 41 with patients under topical anesthesia and sedation, 5 with patients under paracervical nerve block, and 19 with patients under conscious sedation. Thirteen complications were reported: 12 related to GA and 1 due to paracervical nerve block. Of complications due to GA, 7 were grade 1 and 5 were grade 2. The complication due to paracervical nerve block (seizure) was grade 3. GA had significantly more complications than topical anesthesia or conscious sedation (both P < 0.001). HDR brachytherapy for cervical cancer under GA has significantly more complications than other methods. Given the increasing use of fractionated 3-channel brachytherapy, further investigation of risks and benefits of anesthetic techniques is required.

Research paper thumbnail of External audit of clinical practice and medical decision making in a new Asian oncology center: Results and implications for both developing and developed nations

International Journal of Radiation Oncology Biology Physics, 2006

Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic f... more Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic factors, including marital/live-in status. Married or men with a live-in partner treated on 3 RTOG head and neck clinical trials had improved local control and overall survival compared to single men while this effect difference did not translate to women. RTOG 97-14 compared 30 Gy in 10 fractions to 8 Gy in 1 fraction in the treatment of patients with symptomatic bone metastases from breast and prostate cancer. The specific aim of this study is to evaluate outcome differences based upon marital status. Materials/Methods: RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Comparisons of re-treatment rates and overall survival were made based upon gender, marital status and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate the time to re-treatment at 36 months and Grays test was used to test for treatment differences within the same groupings. Survival differences were evaluated by means of the log rank test. Marital status, gender, KPS and treatment were variables tested in a univariate Cox model evaluating the time to re-treatment. Results: Women and men receiving 30 Gy had a significantly longer time to re-treatment compared to patients receiving 8 Gy, pϽ0.0001 and pϽ0.026 respectively. Women lived significantly longer than men, regardless of treatment arm (median survival of females and males is 11.8 and 7.8 months, respectively, pϽ0.0001). Married men and women and single women receiving 30 Gy had significantly longer time to re-treatment, pϭ0.007, pϭ0.0052, and pϭ0.0009 respectively. We failed to show a difference in re-treatment rates in single men receiving either 30 Gy or 8 Gy. Re-treatment rates were higher in married and single women receiving 8 Gy regardless of KPS while only men with initial KPS of 70 -80 had fewer re-treatments from 30 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive re-treatment, pϽ0.0001, with a trend towards single patients not receiving re-treatment, pϭ0.07. Conclusions: Non-disease related variables, like social support, might influence the results of clinical trials with subjective end-points such as re-treatment rates. The lower re-treatment rates observed in single male patients receiving 8 Gy may be a result of the lack of adequate social support systems in place to facilitate additional care. Clinicians may need to be sensitive to the greater likelihood of negative outcomes in single male patients but more focused strategies depend on better specification of what aspects of being single are most disadvantageous to men with cancer.

Research paper thumbnail of Variability in estimating late normal tissue toxicity for patients receiving radiotherapy. Does experience influence what we are telling our patients

European Journal of Cancer, 2001

Research paper thumbnail of External audit of clinical practice and medical decision making in a new Asian oncology center: Results and implications for both developing and developed nations

International Journal of Radiation Oncology Biology Physics, 2006

Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic f... more Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic factors, including marital/live-in status. Married or men with a live-in partner treated on 3 RTOG head and neck clinical trials had improved local control and overall survival compared to single men while this effect difference did not translate to women. RTOG 97-14 compared 30 Gy in 10 fractions to 8 Gy in 1 fraction in the treatment of patients with symptomatic bone metastases from breast and prostate cancer. The specific aim of this study is to evaluate outcome differences based upon marital status. Materials/Methods: RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Comparisons of re-treatment rates and overall survival were made based upon gender, marital status and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate the time to re-treatment at 36 months and Grays test was used to test for treatment differences within the same groupings. Survival differences were evaluated by means of the log rank test. Marital status, gender, KPS and treatment were variables tested in a univariate Cox model evaluating the time to re-treatment. Results: Women and men receiving 30 Gy had a significantly longer time to re-treatment compared to patients receiving 8 Gy, pϽ0.0001 and pϽ0.026 respectively. Women lived significantly longer than men, regardless of treatment arm (median survival of females and males is 11.8 and 7.8 months, respectively, pϽ0.0001). Married men and women and single women receiving 30 Gy had significantly longer time to re-treatment, pϭ0.007, pϭ0.0052, and pϭ0.0009 respectively. We failed to show a difference in re-treatment rates in single men receiving either 30 Gy or 8 Gy. Re-treatment rates were higher in married and single women receiving 8 Gy regardless of KPS while only men with initial KPS of 70 -80 had fewer re-treatments from 30 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive re-treatment, pϽ0.0001, with a trend towards single patients not receiving re-treatment, pϭ0.07. Conclusions: Non-disease related variables, like social support, might influence the results of clinical trials with subjective end-points such as re-treatment rates. The lower re-treatment rates observed in single male patients receiving 8 Gy may be a result of the lack of adequate social support systems in place to facilitate additional care. Clinicians may need to be sensitive to the greater likelihood of negative outcomes in single male patients but more focused strategies depend on better specification of what aspects of being single are most disadvantageous to men with cancer.

Research paper thumbnail of Efficacy of an integrated continuing medical education (CME) and quality improvement (QI) program on radiation oncologist (RO) clinical practice

International Journal of Radiation Oncology Biology Physics, 2006

Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical ... more Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical education (CME) or quality improvement (QI) program efficacy. Our aim was to evaluate a CME/QI program for changes in RO behavior, performance, and adherence to department protocols/studies over the first 12 months of the program. Methods and Materials: The CME/QI program combined chart audit with feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and targeted CME tutorials. Between April 2003 and March 2004, management of 75 patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via simulation review audit (SR-AWF) using a validated instrument. Scores were presented, and case management was discussed with individualized educational feedback. RO behavior and performance was compared over the first year of the program. Results: Comparing the first and second 6 months, there was a significant improvement in mean behavior (12.7-13.6 of 14, p ‫؍‬ 0.0005) and RO performance (7.6 -7.9 of 8, p ‫؍‬ 0.018) scores. Protocol/study adherence significantly improved from 90.3% to 96.6% (p ‫؍‬ 0.005). A total of 50 actions were generated, including the identification of learning needs to direct CME tutorials, the systematic change of suboptimal RO practice, and the alteration of deficient management of 3% of patients audited during the program. Conclusion: An integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME tutorials effectively improved targeted RO behavior and performance over a 12-month period. There was a corresponding increase in departmental protocol and study adherence.

Research paper thumbnail of The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

International Journal of Radiation Oncology Biology Physics, 2007

Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic... more Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at The Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38 -90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

Research paper thumbnail of Phase II study of the American Brachytherapy Society guidelines for the use of high-dose rate brachytherapy in the treatment of cervical carcinoma: is 45-50.4 Gy radiochemotherapy plus 31.8 Gy in six fractions high-dose rate brachytherapy tolerable

International Journal of Gynecological Cancer, 2006

Abstract. Shakespeare TP, Lim KHC, Lee KM, Back MF, Mukherjee R, Lu JD. Phase II study of the Am... more Abstract. Shakespeare TP, Lim KHC, Lee KM, Back MF, Mukherjee R, Lu JD. Phase II study of the American Brachytherapy Society guidelines for the use of high–dose rate brachytherapy in the treatment of cervical carcinoma: is 45–50.4 Gy radiochemotherapy plus 31.8 Gy in six fractions high–dose rate brachytherapy tolerable? Int J Gynecol Cancer 2006;16:277–282.In 2000, the American Brachytherapy Society (ABS) published incompletely evaluated guidelines for curative chemoradiation and high–dose rate (HDR) brachytherapy for cervical cancer: our aim was to assess guideline tolerability in an Asian population. From 2000, all stage I–IVA cervical carcinoma patients were treated following ABS guidelines. Early disease (FIGO stage I/II <4 cm) received 45 Gy whole-pelvis external-beam radiation (EBRT) at 1.8 Gy/fraction, while advanced-stage disease received 50.4 Gy: no central shielding was used. All patients were planned to receive chemotherapy during EBRT, cisplatin 40 mg/m2 weekly. All patients received 31.8-Gy HDR brachytherapy (six fractions of 5.3 Gy/fraction) to point A via three-channel applicators. Radiotherapy was completed within 8 weeks. Toxicity scoring used Common Toxicity Criteria. Nineteen of 21 (90.4%) patients (8 early, 13 advanced stage) received planned radiation, and 85.7% received planned chemotherapy. Median follow-up was 24 months (range 9–50 months). Three-year overall survival (S) was 79.1% and disease-free survival (DFS) was 64.8%. S/DFS for early and advanced stage was 85.7%/85.7% and 73.3%/47.1%, respectively. Complete response (CR) was achieved by 85.7% of patients, partial response 14.3%. For those in CR, there were no local failures. Acute cystitis occurred in 23.8%, proctitis 4.8%, and gastroenteritis 47.6%. Late cystitis occurred in 9.5%, gastroenteritis 4.8%, and genitourinary fistula (in the presence of progressive disease) 4.8%. No grade 3/4 treatment-related toxicity occurred. The ABS guidelines were well tolerated and efficacious in our study, although longer follow-up is required. Further studies are warranted to validate safety and efficacy of the recommendations.

Research paper thumbnail of Interpreting the improved outcome of patients with central nervous system metastases managed in clinical trials compared with standard hospital practice

Australasian Radiology, 2005

The aims were to determine the median survival and prognostic factors of patients with central ne... more The aims were to determine the median survival and prognostic factors of patients with central nervous system (CNS) metastases managed with whole-brain radiation therapy (WBRT), and to explore selection criteria in recently published clinical trials using aggressive interventions in CNS metastases. A retrospective audit was performed on patients managed with WBRT for CNS metastases. Potential prognostic factors were recorded and analysed for their association with survival duration. The proportion of patients with these factors was also compared with those of patients managed under three recently reported studies investigating aggressive interventions, such as radiosurgery and chemotherapy for CNS metastases. Seventy-three patients were treated with WBRT for cerebral metastases over a 12-month period. The median survival of the population was 3.4 months (95% confidence interval: 2.7–4.1), with 6- and 12-month survival rates of 30 and 18%, respectively. Significant prognostic factors for prolonged median survival were Eastern Cooperative Oncology Group status 0–2 (P = 0.015), Medical Research Council neurological functional status 0–1 (P = 0.006), and Recursive Partitioning Analysis Class 2 versus Class 3 (P = 0.020). On multivariate analysis, younger patient age (P = 0.02) and better performance status (P < 0.01) were associated with improved outcome. When comparing these characteristics with selected published studies, our study cohort demonstrated a higher proportion of patients with poor performance status, a greater number of metastases per patient and a higher incidence of extracranial disease. This reflects the selected nature of patients in these published studies. Central nervous system metastases confer a poor prognosis and, for the majority of patients, aggressive interventions are unlikely to improve survival. The use of potentially toxic and expensive treatments should be reserved for those few in whom these studies have shown a potential benefit.

Research paper thumbnail of Effect of an integrated continuing medical education (CME) and quality improvement (QI) program on radiation oncologist (RO) clinical practice

International Journal of Radiation Oncology Biology Physics, 2004

Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical ... more Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical education (CME) or quality improvement (QI) program efficacy. Our aim was to evaluate a CME/QI program for changes in RO behavior, performance, and adherence to department protocols/studies over the first 12 months of the program. Methods and Materials: The CME/QI program combined chart audit with feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and targeted CME tutorials. Between April 2003 and March 2004, management of 75 patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via simulation review audit (SR-AWF) using a validated instrument. Scores were presented, and case management was discussed with individualized educational feedback. RO behavior and performance was compared over the first year of the program. Results: Comparing the first and second 6 months, there was a significant improvement in mean behavior (12.7-13.6 of 14, p ‫؍‬ 0.0005) and RO performance (7.6 -7.9 of 8, p ‫؍‬ 0.018) scores. Protocol/study adherence significantly improved from 90.3% to 96.6% (p ‫؍‬ 0.005). A total of 50 actions were generated, including the identification of learning needs to direct CME tutorials, the systematic change of suboptimal RO practice, and the alteration of deficient management of 3% of patients audited during the program. Conclusion: An integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME tutorials effectively improved targeted RO behavior and performance over a 12-month period. There was a corresponding increase in departmental protocol and study adherence.

Research paper thumbnail of Evaluation of the efficacy of a targeted continuing medical education (CME) intervention for radiation oncologists (ROs

International Journal of Radiation Oncology Biology Physics, 2003

Research paper thumbnail of Evaluation of a radiotherapy protocol based on INT0116 for completely resected gastric adenocarcinoma

International Journal of Radiation Oncology Biology Physics, 2004

With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatme... more With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatment after complete resection of gastric adenocarcinoma. However, the implementation of radiotherapy (RT) remains a concern. In response, consensus guidelines on RT technique have been published. Our objective was to measure the inter- and intraclinician variability in RT field delineation using conventional two- (2D) and three-dimensional (3D) techniques. Between 1999 and 2003, five radiation oncologists (ROs) treated 45 patients with completely resected, gastric adenocarcinoma using postoperative radiochemotherapy (INT0116). Two cases were included in this study (Patient 1 had cardia and Patient 2 had antral disease). Standardized vignettes (with surgical and pathologic findings) and preoperative and postoperative imaging for each case were developed. Each RO designed AP-PA fields for each patient (2D planning) on two separate occasions. This was repeated using a 3D planning technique. Patient 1 had a mean field area of 250.2 cm(2) (SD 12.0) and 227.9 cm(2) (SD 26.5) using 2D and 3D planning, respectively (p = 0.03). The mean clinical target volume (CTV) volume was 468.3 cm(3) (SD 65.9). Patient 1 had a significantly greater inter- than intra-RO variation for the field area designed with 3D planning; however, no difference occurred with 2D planning or CTV contouring. Patient 2 had a mean field area of 234.8 cm(2) (SD 33.1) and 226.8 cm(2) (SD 19.3) using 2D and 3D planning, respectively (p = 0.5). The mean CTV was 729.4 cm(3) (SD 67.3). For Patient 2, the inter-RO variability was significantly greater than the intra-RO variability for the field area using both 2D and 3D planning, and no difference was seen for the CTV. Composite beam&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s-eye-view plots revealed that the superior, inferior, and right lateral borders proved to be most contentious. Despite published guidelines and a departmental protocol, significant variations in the RT field areas were seen among ROs for both 2D and 3D planning. However, in general, CTV contouring was reproducible. Because 3D-RT hinges on accurate target identification, caution should be exercised before migrating to 3D planning for postoperative gastric cancer.

Research paper thumbnail of Evaluation of a radiotherapy protocol based on INT0116 for completely resected gastric adenocarcinoma

International Journal of Radiation Oncology Biology Physics, 2003

With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatme... more With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatment after complete resection of gastric adenocarcinoma. However, the implementation of radiotherapy (RT) remains a concern. In response, consensus guidelines on RT technique have been published. Our objective was to measure the inter- and intraclinician variability in RT field delineation using conventional two- (2D) and three-dimensional (3D) techniques. Between 1999 and 2003, five radiation oncologists (ROs) treated 45 patients with completely resected, gastric adenocarcinoma using postoperative radiochemotherapy (INT0116). Two cases were included in this study (Patient 1 had cardia and Patient 2 had antral disease). Standardized vignettes (with surgical and pathologic findings) and preoperative and postoperative imaging for each case were developed. Each RO designed AP-PA fields for each patient (2D planning) on two separate occasions. This was repeated using a 3D planning technique. Patient 1 had a mean field area of 250.2 cm(2) (SD 12.0) and 227.9 cm(2) (SD 26.5) using 2D and 3D planning, respectively (p = 0.03). The mean clinical target volume (CTV) volume was 468.3 cm(3) (SD 65.9). Patient 1 had a significantly greater inter- than intra-RO variation for the field area designed with 3D planning; however, no difference occurred with 2D planning or CTV contouring. Patient 2 had a mean field area of 234.8 cm(2) (SD 33.1) and 226.8 cm(2) (SD 19.3) using 2D and 3D planning, respectively (p = 0.5). The mean CTV was 729.4 cm(3) (SD 67.3). For Patient 2, the inter-RO variability was significantly greater than the intra-RO variability for the field area using both 2D and 3D planning, and no difference was seen for the CTV. Composite beam&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s-eye-view plots revealed that the superior, inferior, and right lateral borders proved to be most contentious. Despite published guidelines and a departmental protocol, significant variations in the RT field areas were seen among ROs for both 2D and 3D planning. However, in general, CTV contouring was reproducible. Because 3D-RT hinges on accurate target identification, caution should be exercised before migrating to 3D planning for postoperative gastric cancer.

Research paper thumbnail of Estimating risks of radiotherapy complications as part of informed consent: the high degree of variability between radiation oncologists may be related to experience

International Journal of Radiation Oncology Biology Physics, 2002

Purpose: Estimating the risks of radiotherapy (RT) toxicity is important for informed consent; ho... more Purpose: Estimating the risks of radiotherapy (RT) toxicity is important for informed consent; however, the consistency in estimates has not been studied. This study aimed to explore the variability and factors affecting risk estimates (REs). Methods and Materials: A survey was mailed to Australian radiation oncologists, who were asked to estimate risks of RT complications given 49 clinical scenarios. The REs were assessed for association with oncologist experience, subspecialization, and private practice. Results: The REs were extremely variable, with a 50-fold median variability. The least variability (sevenfold) was for estimates of late, small intestinal perforation/obstruction after a one-third volume received 50 Gy with concurrent 5-fluorouracil (RE range 5-35%). The variation between the smallest and largest REs in 17 scenarios was >100-fold. The years of experience was significantly associated with REs of soft/connective-tissue toxicity (p ‫؍‬ 0.01) but inversely associated with estimates of neurologic/central nervous system toxicity (p ‫؍‬ 0.08). Ninety-six percent of respondents believed REs were important to RT practice; only 24% rated evidence to support their estimates as good. Sixty-seven percent believed national/international groups should pursue the issue further. Conclusion: Enormous variability exists in REs for normal tissue complications due to RT that is influenced by the years of experience. Risk estimation is perceived as an important issue without a good evidence base. Additional studies are strongly recommended.

Research paper thumbnail of Adjuvant High-Dose Rate Brachytherapy After Chemoradiation for Treatment of Early T-Stage Nasopharyngeal Carcinoma

American Journal of Clinical Oncology-cancer Clinical Trials, 2004

The local control of nasopharyngeal carcinoma after conventional radiotherapy has historically be... more The local control of nasopharyngeal carcinoma after conventional radiotherapy has historically been suboptimal. Recently, investigators have reported improved outcomes for this patient population with the use of combined chemoradiotherapy. The purpose of this analysis of our prospective treatment protocol was to evaluate the additional value of high-dose rate intracavitary brachytherapy (HDRIB) on the disease response, local control, and survival. Between March 1999 and January 2001, 16 patients with newly diagnosed locally advanced (stage III and IV) nasopharyngeal carcinoma were treated prospectively at the Radiation Oncology Department of the National University Hospital of Singapore. All patients were staged according to the AJCC (1997) Staging System and had early T stages (T1 and T2). Treatments included concurrent external beam radiotherapy (EBRT) and chemotherapy as follows: 66 Gy to the primary tumor in conventional fractionation with cisplatin based concurrent chemotherapy followed by adjuvant cisplatin and 5-fluorouracil (5-FU) chemotherapy. Ten Gy of HDRIB in 2 weekly fractions were delivered after the completion of EBRT to all 16 patients. All patients were evaluable for treatment response, local control, survival, and toxicity analysis. The median follow-up for the whole group of patients was 18 months (range: 10-34 months). All patients obtained pathologic complete response at the primary site at 4 months after the completion of the treatment. At the time of this analysis, 15 (93.8%) patients are alive with no evidence of disease. One patient (6.2%) developed locoregional recurrence in the neck at 9 months, and distant metastasis at 11 months after the completion of treatment. Our experience has shown adjuvant HDRIB after concurrent chemoradiation offers encouraging disease response, local control, and survival. A prospective study is being planned to further evaluate the role of adjuvant HDRIB after concurrent chemoradiation on treatment outcome.

Research paper thumbnail of A comparison of RANZCR and Singapore-designed radiation oncology practice audit instruments: How does reproducibility affect future approaches to revalidation

Australasian Radiology, 2004

Physician competency assessment requires the use of validated methods and instruments. The Royal ... more Physician competency assessment requires the use of validated methods and instruments. The Royal Australian and New Zealand College of Radiologists (RANZCR) developed a draft audit form to be evaluated as a competency assessment instrument for radiation oncologists (ROs) in Australasia. We evaluated the reliability of the RANZCR instrument as well as a separate The Cancer Institute (TCI) Singapore-designed instrument by having two ROs perform an independent chart review of 80 randomly selected patients seen at The Cancer Institute (TCI), Singapore. Both RANZCR and TCI Singapore instruments were used to score each chart. Inter-and intra-observer reliability for both audit instruments were compared using misclassification rates as the primary end-point. Overall, for inter-observer reproducibility, 2.3% of TCI Singapore items were misclassified compared to 22.3% of RANZCR items ( P < 0.0001, 100.00% confidence that TCI instrument has less inter-observer misclassification). For intra-observer reproducibility, 2.4% of TCI Singapore items were misclassified compared to 13.6% of RANZCR items ( P < 0.0001, 100.00% confidence that TCI instrument has less intra-observer misclassification). The proposed RANZCR RO revalidation audit instrument requires further refinement to improve validity. Several items require modification or removal because of lack of reliability, whereas inclusion of other important and reproducible items can be incorporated as demonstrated by the TCI Singapore instrument. The TCI Singapore instrument also has the advantage of incorporating a simple scoring system and criticality index to allow discrimination between ROs and comparisons against future College standards.

Research paper thumbnail of Outcomes of Adjuvant Chemoradiotherapy After a Radical Gastrectomy and a D2 Node Dissection for Gastric Adenocarcinoma

Cancer Journal, 2008

Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resect... more Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resected high-risk adenocarcinoma of the stomach in the United States. However, adjuvant chemoradiation remains controversial in many parts of Asia and Europe, where patients tend to undergo a more thorough D2 dissection. In INT-0116, 90% of patients had a limited or inadequate node dissection (D0 or D1). Also, 17% of patients in the chemoradiation arm had to discontinue treatment because of toxicities. The objectives of this retrospective study are to report the clinical outcomes of a cohort of patients who were mostly treated with a D2 node dissection and received adjuvant chemoradiation as per INT-0116, and the toxicities of chemoradiation in the context of more aggressive surgery. After the results of INT-0116 became apparent, we adopted an institutional policy whereby patients who would otherwise fit the inclusion criteria of INT-0116 received adjuvant chemoradiation. Between March 1999 and November 2004, 70 consecutive patients with pathologic stage T3, T4, or node-positive disease were treated according to the chemoradiation arm of INT-0116. Patients received intravenous 5-fluorouracil 425 mg/m and leucovorin 20 mg/m in cycles 1, 3, and 4. Concurrent chemoradiation was given in cycle 2 and consisted of bolus 5-fluorouracil and leucovorin and radiotherapy (45 Gy over 25 fractions in 5 weeks). All patients were operated on by dedicated Japan-trained Surgical Oncologists. Sixty-seven patients (96%) had a D2 nodal dissection. Sixty-five patients (93%) had negative pathologic margins (R0 resection) and 5 (7%) had microscopically involved margins (R1 resection). The median follow-up was 27 months (range, 10.1-60.3). The 3-year overall survival, disease-free survival, and local control were 60.6%, 54.1%, and 84.3%, respectively. Of the 30 patients who relapsed, 5 (17%) had isolated locoregional recurrences only. The National Cancer Institute--Common Terminology Criteria version 3.0 acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 15.7% and 4.3%, respectively. Toxicities led to chemotherapy dose-reductions in 18 patients and dose-delay in 19 patients. Including chemotherapy dose-reductions and delays, 66 patients (94%) completed the entire chemoradiation regimen. There were no toxicity-related deaths. In our cohort of 70 patients who had a more thorough D2 node dissection, adjuvant chemoradiation was well tolerated with acceptable toxicities and reasonable tumor control.

Research paper thumbnail of Internal Audit of a Comprehensive IMRT Program for Prostate Cancer: A Model for Centers in Developing Countries

International Journal of Radiation Oncology Biology Physics, 2009

With improving regional prosperity, significant capital investments have been made to rapidly exp... more With improving regional prosperity, significant capital investments have been made to rapidly expand radiotherapy capacity across Southeast Asia. Yet little has been reported on the implementation of adequate quality assurance (QA) in patient management. The objective of this study is to perform an in-depth QA assessment of our definitive intensity-modulated radiotherapy (IMRT) program for prostate cancer since its inception. The department&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s prostate IMRT program was modeled after that of the University of California San Francisco. A departmental protocol consisting of radiotherapy volume/dose and hormone sequencing/duration and a set of 18 dose objectives to the target and critical organs were developed, and all plans were presented at the weekly departmental QA rounds. All patients treated with definitive IMRT for nonmetastatic prostate cancer were retrospectively reviewed. Protocol adherence, dosimetry data, toxicities, and outcomes were evaluated. Since 2005, 76 patients received IMRT: 54 with whole-pelvis and 22 with prostate-only treatment. Of the 1,140 recorded dosimetric end points, 39 (3.3%) did not meet the protocol criteria. At QA rounds, no plans required a revision. Only one major protocol violation was observed. Two and two cases of Grade 3-4 acute and late toxicities, respectively, were observed. Five (8.8%) patients developed proctitis, but only one required argon laser therapy. Our comprehensive, practice-adapted QA measures appeared to ensure that we were able to consistently generate conforming IMRT plans with acceptable toxicities. These measures can be easily integrated into other clinics contemplating on developing such a program.

Research paper thumbnail of External Audit of Clinical Practice and Medical Decision-Making in a New Asian Oncology Center: Results and Implications for Both Developing and Developed Nations

International Journal of Radiation Oncology Biology Physics, 2005

Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic f... more Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic factors, including marital/live-in status. Married or men with a live-in partner treated on 3 RTOG head and neck clinical trials had improved local control and overall survival compared to single men while this effect difference did not translate to women. RTOG 97-14 compared 30 Gy in 10 fractions to 8 Gy in 1 fraction in the treatment of patients with symptomatic bone metastases from breast and prostate cancer. The specific aim of this study is to evaluate outcome differences based upon marital status. Materials/Methods: RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Comparisons of re-treatment rates and overall survival were made based upon gender, marital status and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate the time to re-treatment at 36 months and Grays test was used to test for treatment differences within the same groupings. Survival differences were evaluated by means of the log rank test. Marital status, gender, KPS and treatment were variables tested in a univariate Cox model evaluating the time to re-treatment. Results: Women and men receiving 30 Gy had a significantly longer time to re-treatment compared to patients receiving 8 Gy, pϽ0.0001 and pϽ0.026 respectively. Women lived significantly longer than men, regardless of treatment arm (median survival of females and males is 11.8 and 7.8 months, respectively, pϽ0.0001). Married men and women and single women receiving 30 Gy had significantly longer time to re-treatment, pϭ0.007, pϭ0.0052, and pϭ0.0009 respectively. We failed to show a difference in re-treatment rates in single men receiving either 30 Gy or 8 Gy. Re-treatment rates were higher in married and single women receiving 8 Gy regardless of KPS while only men with initial KPS of 70 -80 had fewer re-treatments from 30 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive re-treatment, pϽ0.0001, with a trend towards single patients not receiving re-treatment, pϭ0.07. Conclusions: Non-disease related variables, like social support, might influence the results of clinical trials with subjective end-points such as re-treatment rates. The lower re-treatment rates observed in single male patients receiving 8 Gy may be a result of the lack of adequate social support systems in place to facilitate additional care. Clinicians may need to be sensitive to the greater likelihood of negative outcomes in single male patients but more focused strategies depend on better specification of what aspects of being single are most disadvantageous to men with cancer.

Research paper thumbnail of A Study of Complications Arising From Different Methods of Anesthesia Used in High-Dose-Rate Brachytherapy for Cervical Cancer

American Journal of Clinical Oncology-cancer Clinical Trials, 2004

The purpose of this report is to review the complications related to different methods of anesthe... more The purpose of this report is to review the complications related to different methods of anesthesia for high-dose-rate (HDR) brachytherapy for cervical carcinoma. All patients diagnosed with cervical cancer between 1999 and 2002 treated with 3-channel HDR brachytherapy were entered. Complications due to anesthesia for each fraction of brachytherapy were graded using the Common Toxicity Criteria. Eighty-four fractions of brachytherapy were delivered to 18 patients: 19 fractions with patients under general anesthesia (GA), 41 with patients under topical anesthesia and sedation, 5 with patients under paracervical nerve block, and 19 with patients under conscious sedation. Thirteen complications were reported: 12 related to GA and 1 due to paracervical nerve block. Of complications due to GA, 7 were grade 1 and 5 were grade 2. The complication due to paracervical nerve block (seizure) was grade 3. GA had significantly more complications than topical anesthesia or conscious sedation (both P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). HDR brachytherapy for cervical cancer under GA has significantly more complications than other methods. Given the increasing use of fractionated 3-channel brachytherapy, further investigation of risks and benefits of anesthetic techniques is required.

Research paper thumbnail of External audit of clinical practice and medical decision making in a new Asian oncology center: Results and implications for both developing and developed nations

International Journal of Radiation Oncology Biology Physics, 2006

Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic f... more Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic factors, including marital/live-in status. Married or men with a live-in partner treated on 3 RTOG head and neck clinical trials had improved local control and overall survival compared to single men while this effect difference did not translate to women. RTOG 97-14 compared 30 Gy in 10 fractions to 8 Gy in 1 fraction in the treatment of patients with symptomatic bone metastases from breast and prostate cancer. The specific aim of this study is to evaluate outcome differences based upon marital status. Materials/Methods: RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Comparisons of re-treatment rates and overall survival were made based upon gender, marital status and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate the time to re-treatment at 36 months and Grays test was used to test for treatment differences within the same groupings. Survival differences were evaluated by means of the log rank test. Marital status, gender, KPS and treatment were variables tested in a univariate Cox model evaluating the time to re-treatment. Results: Women and men receiving 30 Gy had a significantly longer time to re-treatment compared to patients receiving 8 Gy, pϽ0.0001 and pϽ0.026 respectively. Women lived significantly longer than men, regardless of treatment arm (median survival of females and males is 11.8 and 7.8 months, respectively, pϽ0.0001). Married men and women and single women receiving 30 Gy had significantly longer time to re-treatment, pϭ0.007, pϭ0.0052, and pϭ0.0009 respectively. We failed to show a difference in re-treatment rates in single men receiving either 30 Gy or 8 Gy. Re-treatment rates were higher in married and single women receiving 8 Gy regardless of KPS while only men with initial KPS of 70 -80 had fewer re-treatments from 30 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive re-treatment, pϽ0.0001, with a trend towards single patients not receiving re-treatment, pϭ0.07. Conclusions: Non-disease related variables, like social support, might influence the results of clinical trials with subjective end-points such as re-treatment rates. The lower re-treatment rates observed in single male patients receiving 8 Gy may be a result of the lack of adequate social support systems in place to facilitate additional care. Clinicians may need to be sensitive to the greater likelihood of negative outcomes in single male patients but more focused strategies depend on better specification of what aspects of being single are most disadvantageous to men with cancer.

Research paper thumbnail of Variability in estimating late normal tissue toxicity for patients receiving radiotherapy. Does experience influence what we are telling our patients

European Journal of Cancer, 2001

Research paper thumbnail of External audit of clinical practice and medical decision making in a new Asian oncology center: Results and implications for both developing and developed nations

International Journal of Radiation Oncology Biology Physics, 2006

Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic f... more Purpose/Objective: The RTOG has previously reported outcome difference based upon socioeconomic factors, including marital/live-in status. Married or men with a live-in partner treated on 3 RTOG head and neck clinical trials had improved local control and overall survival compared to single men while this effect difference did not translate to women. RTOG 97-14 compared 30 Gy in 10 fractions to 8 Gy in 1 fraction in the treatment of patients with symptomatic bone metastases from breast and prostate cancer. The specific aim of this study is to evaluate outcome differences based upon marital status. Materials/Methods: RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Comparisons of re-treatment rates and overall survival were made based upon gender, marital status and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate the time to re-treatment at 36 months and Grays test was used to test for treatment differences within the same groupings. Survival differences were evaluated by means of the log rank test. Marital status, gender, KPS and treatment were variables tested in a univariate Cox model evaluating the time to re-treatment. Results: Women and men receiving 30 Gy had a significantly longer time to re-treatment compared to patients receiving 8 Gy, pϽ0.0001 and pϽ0.026 respectively. Women lived significantly longer than men, regardless of treatment arm (median survival of females and males is 11.8 and 7.8 months, respectively, pϽ0.0001). Married men and women and single women receiving 30 Gy had significantly longer time to re-treatment, pϭ0.007, pϭ0.0052, and pϭ0.0009 respectively. We failed to show a difference in re-treatment rates in single men receiving either 30 Gy or 8 Gy. Re-treatment rates were higher in married and single women receiving 8 Gy regardless of KPS while only men with initial KPS of 70 -80 had fewer re-treatments from 30 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive re-treatment, pϽ0.0001, with a trend towards single patients not receiving re-treatment, pϭ0.07. Conclusions: Non-disease related variables, like social support, might influence the results of clinical trials with subjective end-points such as re-treatment rates. The lower re-treatment rates observed in single male patients receiving 8 Gy may be a result of the lack of adequate social support systems in place to facilitate additional care. Clinicians may need to be sensitive to the greater likelihood of negative outcomes in single male patients but more focused strategies depend on better specification of what aspects of being single are most disadvantageous to men with cancer.

Research paper thumbnail of Efficacy of an integrated continuing medical education (CME) and quality improvement (QI) program on radiation oncologist (RO) clinical practice

International Journal of Radiation Oncology Biology Physics, 2006

Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical ... more Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical education (CME) or quality improvement (QI) program efficacy. Our aim was to evaluate a CME/QI program for changes in RO behavior, performance, and adherence to department protocols/studies over the first 12 months of the program. Methods and Materials: The CME/QI program combined chart audit with feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and targeted CME tutorials. Between April 2003 and March 2004, management of 75 patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via simulation review audit (SR-AWF) using a validated instrument. Scores were presented, and case management was discussed with individualized educational feedback. RO behavior and performance was compared over the first year of the program. Results: Comparing the first and second 6 months, there was a significant improvement in mean behavior (12.7-13.6 of 14, p ‫؍‬ 0.0005) and RO performance (7.6 -7.9 of 8, p ‫؍‬ 0.018) scores. Protocol/study adherence significantly improved from 90.3% to 96.6% (p ‫؍‬ 0.005). A total of 50 actions were generated, including the identification of learning needs to direct CME tutorials, the systematic change of suboptimal RO practice, and the alteration of deficient management of 3% of patients audited during the program. Conclusion: An integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME tutorials effectively improved targeted RO behavior and performance over a 12-month period. There was a corresponding increase in departmental protocol and study adherence.

Research paper thumbnail of The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

International Journal of Radiation Oncology Biology Physics, 2007

Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic... more Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at The Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38 -90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

Research paper thumbnail of Phase II study of the American Brachytherapy Society guidelines for the use of high-dose rate brachytherapy in the treatment of cervical carcinoma: is 45-50.4 Gy radiochemotherapy plus 31.8 Gy in six fractions high-dose rate brachytherapy tolerable

International Journal of Gynecological Cancer, 2006

Abstract. Shakespeare TP, Lim KHC, Lee KM, Back MF, Mukherjee R, Lu JD. Phase II study of the Am... more Abstract. Shakespeare TP, Lim KHC, Lee KM, Back MF, Mukherjee R, Lu JD. Phase II study of the American Brachytherapy Society guidelines for the use of high–dose rate brachytherapy in the treatment of cervical carcinoma: is 45–50.4 Gy radiochemotherapy plus 31.8 Gy in six fractions high–dose rate brachytherapy tolerable? Int J Gynecol Cancer 2006;16:277–282.In 2000, the American Brachytherapy Society (ABS) published incompletely evaluated guidelines for curative chemoradiation and high–dose rate (HDR) brachytherapy for cervical cancer: our aim was to assess guideline tolerability in an Asian population. From 2000, all stage I–IVA cervical carcinoma patients were treated following ABS guidelines. Early disease (FIGO stage I/II <4 cm) received 45 Gy whole-pelvis external-beam radiation (EBRT) at 1.8 Gy/fraction, while advanced-stage disease received 50.4 Gy: no central shielding was used. All patients were planned to receive chemotherapy during EBRT, cisplatin 40 mg/m2 weekly. All patients received 31.8-Gy HDR brachytherapy (six fractions of 5.3 Gy/fraction) to point A via three-channel applicators. Radiotherapy was completed within 8 weeks. Toxicity scoring used Common Toxicity Criteria. Nineteen of 21 (90.4%) patients (8 early, 13 advanced stage) received planned radiation, and 85.7% received planned chemotherapy. Median follow-up was 24 months (range 9–50 months). Three-year overall survival (S) was 79.1% and disease-free survival (DFS) was 64.8%. S/DFS for early and advanced stage was 85.7%/85.7% and 73.3%/47.1%, respectively. Complete response (CR) was achieved by 85.7% of patients, partial response 14.3%. For those in CR, there were no local failures. Acute cystitis occurred in 23.8%, proctitis 4.8%, and gastroenteritis 47.6%. Late cystitis occurred in 9.5%, gastroenteritis 4.8%, and genitourinary fistula (in the presence of progressive disease) 4.8%. No grade 3/4 treatment-related toxicity occurred. The ABS guidelines were well tolerated and efficacious in our study, although longer follow-up is required. Further studies are warranted to validate safety and efficacy of the recommendations.

Research paper thumbnail of Interpreting the improved outcome of patients with central nervous system metastases managed in clinical trials compared with standard hospital practice

Australasian Radiology, 2005

The aims were to determine the median survival and prognostic factors of patients with central ne... more The aims were to determine the median survival and prognostic factors of patients with central nervous system (CNS) metastases managed with whole-brain radiation therapy (WBRT), and to explore selection criteria in recently published clinical trials using aggressive interventions in CNS metastases. A retrospective audit was performed on patients managed with WBRT for CNS metastases. Potential prognostic factors were recorded and analysed for their association with survival duration. The proportion of patients with these factors was also compared with those of patients managed under three recently reported studies investigating aggressive interventions, such as radiosurgery and chemotherapy for CNS metastases. Seventy-three patients were treated with WBRT for cerebral metastases over a 12-month period. The median survival of the population was 3.4 months (95% confidence interval: 2.7–4.1), with 6- and 12-month survival rates of 30 and 18%, respectively. Significant prognostic factors for prolonged median survival were Eastern Cooperative Oncology Group status 0–2 (P = 0.015), Medical Research Council neurological functional status 0–1 (P = 0.006), and Recursive Partitioning Analysis Class 2 versus Class 3 (P = 0.020). On multivariate analysis, younger patient age (P = 0.02) and better performance status (P < 0.01) were associated with improved outcome. When comparing these characteristics with selected published studies, our study cohort demonstrated a higher proportion of patients with poor performance status, a greater number of metastases per patient and a higher incidence of extracranial disease. This reflects the selected nature of patients in these published studies. Central nervous system metastases confer a poor prognosis and, for the majority of patients, aggressive interventions are unlikely to improve survival. The use of potentially toxic and expensive treatments should be reserved for those few in whom these studies have shown a potential benefit.

Research paper thumbnail of Effect of an integrated continuing medical education (CME) and quality improvement (QI) program on radiation oncologist (RO) clinical practice

International Journal of Radiation Oncology Biology Physics, 2004

Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical ... more Purpose: There has been little radiation oncologist (RO)-specific research in continuing medical education (CME) or quality improvement (QI) program efficacy. Our aim was to evaluate a CME/QI program for changes in RO behavior, performance, and adherence to department protocols/studies over the first 12 months of the program. Methods and Materials: The CME/QI program combined chart audit with feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and targeted CME tutorials. Between April 2003 and March 2004, management of 75 patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via simulation review audit (SR-AWF) using a validated instrument. Scores were presented, and case management was discussed with individualized educational feedback. RO behavior and performance was compared over the first year of the program. Results: Comparing the first and second 6 months, there was a significant improvement in mean behavior (12.7-13.6 of 14, p ‫؍‬ 0.0005) and RO performance (7.6 -7.9 of 8, p ‫؍‬ 0.018) scores. Protocol/study adherence significantly improved from 90.3% to 96.6% (p ‫؍‬ 0.005). A total of 50 actions were generated, including the identification of learning needs to direct CME tutorials, the systematic change of suboptimal RO practice, and the alteration of deficient management of 3% of patients audited during the program. Conclusion: An integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME tutorials effectively improved targeted RO behavior and performance over a 12-month period. There was a corresponding increase in departmental protocol and study adherence.

Research paper thumbnail of Evaluation of the efficacy of a targeted continuing medical education (CME) intervention for radiation oncologists (ROs

International Journal of Radiation Oncology Biology Physics, 2003

Research paper thumbnail of Evaluation of a radiotherapy protocol based on INT0116 for completely resected gastric adenocarcinoma

International Journal of Radiation Oncology Biology Physics, 2004

With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatme... more With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatment after complete resection of gastric adenocarcinoma. However, the implementation of radiotherapy (RT) remains a concern. In response, consensus guidelines on RT technique have been published. Our objective was to measure the inter- and intraclinician variability in RT field delineation using conventional two- (2D) and three-dimensional (3D) techniques. Between 1999 and 2003, five radiation oncologists (ROs) treated 45 patients with completely resected, gastric adenocarcinoma using postoperative radiochemotherapy (INT0116). Two cases were included in this study (Patient 1 had cardia and Patient 2 had antral disease). Standardized vignettes (with surgical and pathologic findings) and preoperative and postoperative imaging for each case were developed. Each RO designed AP-PA fields for each patient (2D planning) on two separate occasions. This was repeated using a 3D planning technique. Patient 1 had a mean field area of 250.2 cm(2) (SD 12.0) and 227.9 cm(2) (SD 26.5) using 2D and 3D planning, respectively (p = 0.03). The mean clinical target volume (CTV) volume was 468.3 cm(3) (SD 65.9). Patient 1 had a significantly greater inter- than intra-RO variation for the field area designed with 3D planning; however, no difference occurred with 2D planning or CTV contouring. Patient 2 had a mean field area of 234.8 cm(2) (SD 33.1) and 226.8 cm(2) (SD 19.3) using 2D and 3D planning, respectively (p = 0.5). The mean CTV was 729.4 cm(3) (SD 67.3). For Patient 2, the inter-RO variability was significantly greater than the intra-RO variability for the field area using both 2D and 3D planning, and no difference was seen for the CTV. Composite beam&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s-eye-view plots revealed that the superior, inferior, and right lateral borders proved to be most contentious. Despite published guidelines and a departmental protocol, significant variations in the RT field areas were seen among ROs for both 2D and 3D planning. However, in general, CTV contouring was reproducible. Because 3D-RT hinges on accurate target identification, caution should be exercised before migrating to 3D planning for postoperative gastric cancer.

Research paper thumbnail of Evaluation of a radiotherapy protocol based on INT0116 for completely resected gastric adenocarcinoma

International Journal of Radiation Oncology Biology Physics, 2003

With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatme... more With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatment after complete resection of gastric adenocarcinoma. However, the implementation of radiotherapy (RT) remains a concern. In response, consensus guidelines on RT technique have been published. Our objective was to measure the inter- and intraclinician variability in RT field delineation using conventional two- (2D) and three-dimensional (3D) techniques. Between 1999 and 2003, five radiation oncologists (ROs) treated 45 patients with completely resected, gastric adenocarcinoma using postoperative radiochemotherapy (INT0116). Two cases were included in this study (Patient 1 had cardia and Patient 2 had antral disease). Standardized vignettes (with surgical and pathologic findings) and preoperative and postoperative imaging for each case were developed. Each RO designed AP-PA fields for each patient (2D planning) on two separate occasions. This was repeated using a 3D planning technique. Patient 1 had a mean field area of 250.2 cm(2) (SD 12.0) and 227.9 cm(2) (SD 26.5) using 2D and 3D planning, respectively (p = 0.03). The mean clinical target volume (CTV) volume was 468.3 cm(3) (SD 65.9). Patient 1 had a significantly greater inter- than intra-RO variation for the field area designed with 3D planning; however, no difference occurred with 2D planning or CTV contouring. Patient 2 had a mean field area of 234.8 cm(2) (SD 33.1) and 226.8 cm(2) (SD 19.3) using 2D and 3D planning, respectively (p = 0.5). The mean CTV was 729.4 cm(3) (SD 67.3). For Patient 2, the inter-RO variability was significantly greater than the intra-RO variability for the field area using both 2D and 3D planning, and no difference was seen for the CTV. Composite beam&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s-eye-view plots revealed that the superior, inferior, and right lateral borders proved to be most contentious. Despite published guidelines and a departmental protocol, significant variations in the RT field areas were seen among ROs for both 2D and 3D planning. However, in general, CTV contouring was reproducible. Because 3D-RT hinges on accurate target identification, caution should be exercised before migrating to 3D planning for postoperative gastric cancer.

Research paper thumbnail of Estimating risks of radiotherapy complications as part of informed consent: the high degree of variability between radiation oncologists may be related to experience

International Journal of Radiation Oncology Biology Physics, 2002

Purpose: Estimating the risks of radiotherapy (RT) toxicity is important for informed consent; ho... more Purpose: Estimating the risks of radiotherapy (RT) toxicity is important for informed consent; however, the consistency in estimates has not been studied. This study aimed to explore the variability and factors affecting risk estimates (REs). Methods and Materials: A survey was mailed to Australian radiation oncologists, who were asked to estimate risks of RT complications given 49 clinical scenarios. The REs were assessed for association with oncologist experience, subspecialization, and private practice. Results: The REs were extremely variable, with a 50-fold median variability. The least variability (sevenfold) was for estimates of late, small intestinal perforation/obstruction after a one-third volume received 50 Gy with concurrent 5-fluorouracil (RE range 5-35%). The variation between the smallest and largest REs in 17 scenarios was >100-fold. The years of experience was significantly associated with REs of soft/connective-tissue toxicity (p ‫؍‬ 0.01) but inversely associated with estimates of neurologic/central nervous system toxicity (p ‫؍‬ 0.08). Ninety-six percent of respondents believed REs were important to RT practice; only 24% rated evidence to support their estimates as good. Sixty-seven percent believed national/international groups should pursue the issue further. Conclusion: Enormous variability exists in REs for normal tissue complications due to RT that is influenced by the years of experience. Risk estimation is perceived as an important issue without a good evidence base. Additional studies are strongly recommended.

Research paper thumbnail of Adjuvant High-Dose Rate Brachytherapy After Chemoradiation for Treatment of Early T-Stage Nasopharyngeal Carcinoma

American Journal of Clinical Oncology-cancer Clinical Trials, 2004

The local control of nasopharyngeal carcinoma after conventional radiotherapy has historically be... more The local control of nasopharyngeal carcinoma after conventional radiotherapy has historically been suboptimal. Recently, investigators have reported improved outcomes for this patient population with the use of combined chemoradiotherapy. The purpose of this analysis of our prospective treatment protocol was to evaluate the additional value of high-dose rate intracavitary brachytherapy (HDRIB) on the disease response, local control, and survival. Between March 1999 and January 2001, 16 patients with newly diagnosed locally advanced (stage III and IV) nasopharyngeal carcinoma were treated prospectively at the Radiation Oncology Department of the National University Hospital of Singapore. All patients were staged according to the AJCC (1997) Staging System and had early T stages (T1 and T2). Treatments included concurrent external beam radiotherapy (EBRT) and chemotherapy as follows: 66 Gy to the primary tumor in conventional fractionation with cisplatin based concurrent chemotherapy followed by adjuvant cisplatin and 5-fluorouracil (5-FU) chemotherapy. Ten Gy of HDRIB in 2 weekly fractions were delivered after the completion of EBRT to all 16 patients. All patients were evaluable for treatment response, local control, survival, and toxicity analysis. The median follow-up for the whole group of patients was 18 months (range: 10-34 months). All patients obtained pathologic complete response at the primary site at 4 months after the completion of the treatment. At the time of this analysis, 15 (93.8%) patients are alive with no evidence of disease. One patient (6.2%) developed locoregional recurrence in the neck at 9 months, and distant metastasis at 11 months after the completion of treatment. Our experience has shown adjuvant HDRIB after concurrent chemoradiation offers encouraging disease response, local control, and survival. A prospective study is being planned to further evaluate the role of adjuvant HDRIB after concurrent chemoradiation on treatment outcome.

Research paper thumbnail of A comparison of RANZCR and Singapore-designed radiation oncology practice audit instruments: How does reproducibility affect future approaches to revalidation

Australasian Radiology, 2004

Physician competency assessment requires the use of validated methods and instruments. The Royal ... more Physician competency assessment requires the use of validated methods and instruments. The Royal Australian and New Zealand College of Radiologists (RANZCR) developed a draft audit form to be evaluated as a competency assessment instrument for radiation oncologists (ROs) in Australasia. We evaluated the reliability of the RANZCR instrument as well as a separate The Cancer Institute (TCI) Singapore-designed instrument by having two ROs perform an independent chart review of 80 randomly selected patients seen at The Cancer Institute (TCI), Singapore. Both RANZCR and TCI Singapore instruments were used to score each chart. Inter-and intra-observer reliability for both audit instruments were compared using misclassification rates as the primary end-point. Overall, for inter-observer reproducibility, 2.3% of TCI Singapore items were misclassified compared to 22.3% of RANZCR items ( P < 0.0001, 100.00% confidence that TCI instrument has less inter-observer misclassification). For intra-observer reproducibility, 2.4% of TCI Singapore items were misclassified compared to 13.6% of RANZCR items ( P < 0.0001, 100.00% confidence that TCI instrument has less intra-observer misclassification). The proposed RANZCR RO revalidation audit instrument requires further refinement to improve validity. Several items require modification or removal because of lack of reliability, whereas inclusion of other important and reproducible items can be incorporated as demonstrated by the TCI Singapore instrument. The TCI Singapore instrument also has the advantage of incorporating a simple scoring system and criticality index to allow discrimination between ROs and comparisons against future College standards.

Research paper thumbnail of Outcomes of Adjuvant Chemoradiotherapy After a Radical Gastrectomy and a D2 Node Dissection for Gastric Adenocarcinoma

Cancer Journal, 2008

Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resect... more Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resected high-risk adenocarcinoma of the stomach in the United States. However, adjuvant chemoradiation remains controversial in many parts of Asia and Europe, where patients tend to undergo a more thorough D2 dissection. In INT-0116, 90% of patients had a limited or inadequate node dissection (D0 or D1). Also, 17% of patients in the chemoradiation arm had to discontinue treatment because of toxicities. The objectives of this retrospective study are to report the clinical outcomes of a cohort of patients who were mostly treated with a D2 node dissection and received adjuvant chemoradiation as per INT-0116, and the toxicities of chemoradiation in the context of more aggressive surgery. After the results of INT-0116 became apparent, we adopted an institutional policy whereby patients who would otherwise fit the inclusion criteria of INT-0116 received adjuvant chemoradiation. Between March 1999 and November 2004, 70 consecutive patients with pathologic stage T3, T4, or node-positive disease were treated according to the chemoradiation arm of INT-0116. Patients received intravenous 5-fluorouracil 425 mg/m and leucovorin 20 mg/m in cycles 1, 3, and 4. Concurrent chemoradiation was given in cycle 2 and consisted of bolus 5-fluorouracil and leucovorin and radiotherapy (45 Gy over 25 fractions in 5 weeks). All patients were operated on by dedicated Japan-trained Surgical Oncologists. Sixty-seven patients (96%) had a D2 nodal dissection. Sixty-five patients (93%) had negative pathologic margins (R0 resection) and 5 (7%) had microscopically involved margins (R1 resection). The median follow-up was 27 months (range, 10.1-60.3). The 3-year overall survival, disease-free survival, and local control were 60.6%, 54.1%, and 84.3%, respectively. Of the 30 patients who relapsed, 5 (17%) had isolated locoregional recurrences only. The National Cancer Institute--Common Terminology Criteria version 3.0 acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 15.7% and 4.3%, respectively. Toxicities led to chemotherapy dose-reductions in 18 patients and dose-delay in 19 patients. Including chemotherapy dose-reductions and delays, 66 patients (94%) completed the entire chemoradiation regimen. There were no toxicity-related deaths. In our cohort of 70 patients who had a more thorough D2 node dissection, adjuvant chemoradiation was well tolerated with acceptable toxicities and reasonable tumor control.

Research paper thumbnail of Internal Audit of a Comprehensive IMRT Program for Prostate Cancer: A Model for Centers in Developing Countries

International Journal of Radiation Oncology Biology Physics, 2009

With improving regional prosperity, significant capital investments have been made to rapidly exp... more With improving regional prosperity, significant capital investments have been made to rapidly expand radiotherapy capacity across Southeast Asia. Yet little has been reported on the implementation of adequate quality assurance (QA) in patient management. The objective of this study is to perform an in-depth QA assessment of our definitive intensity-modulated radiotherapy (IMRT) program for prostate cancer since its inception. The department&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s prostate IMRT program was modeled after that of the University of California San Francisco. A departmental protocol consisting of radiotherapy volume/dose and hormone sequencing/duration and a set of 18 dose objectives to the target and critical organs were developed, and all plans were presented at the weekly departmental QA rounds. All patients treated with definitive IMRT for nonmetastatic prostate cancer were retrospectively reviewed. Protocol adherence, dosimetry data, toxicities, and outcomes were evaluated. Since 2005, 76 patients received IMRT: 54 with whole-pelvis and 22 with prostate-only treatment. Of the 1,140 recorded dosimetric end points, 39 (3.3%) did not meet the protocol criteria. At QA rounds, no plans required a revision. Only one major protocol violation was observed. Two and two cases of Grade 3-4 acute and late toxicities, respectively, were observed. Five (8.8%) patients developed proctitis, but only one required argon laser therapy. Our comprehensive, practice-adapted QA measures appeared to ensure that we were able to consistently generate conforming IMRT plans with acceptable toxicities. These measures can be easily integrated into other clinics contemplating on developing such a program.