Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

Stroke Risk in Survivors of Head and Neck Cancer.

Importance: Survivors of head and neck cancers (HNC) have increased risk of stroke. A comprehensive report using standardized methods is warranted to characterize the risk and to inform on survivorship strategy. Objective: To determine the stroke risk in subpopulations of survivors of HNC in Singapore. Design, Setting, and Participants: This national, registry-based, cross-sectional study aimed to estimate stroke risk in subgroups of the HNC population between January 2005 and December 2020. Participants were identified from the Singapore Cancer Registry, the Singapore Stroke Registry, and the Registry of Birth and Deaths using relevant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes. HNC subgroups were defined based on patient demographic, disease, and treatment factors. Data were analyzed from September 2022 to September 2023. Exposure: Diagnosis of HNC. Main Outcomes and Measures: Both ischemic and hemorrhagic stroke were studied. The age-standardized incidence rate ratio (SIRR) and age-standardized incidence rate difference (SIRD) were reported. The Singapore general population (approximately 4 million) served as the reference group for these estimations. Results: A total of 9803 survivors of HNC (median [IQR] age at diagnosis, 58 [49-68] years; 7166 [73.1%] male) were identified. The most common HNC subsites were nasopharynx (4680 individuals [47.7%]), larynx (1228 individuals [12.5%]), and tongue (1059 individuals [10.8%]). A total of 337 individuals (3.4%) developed stroke over a median (IQR) follow-up of 42.5 (15.0-94.5) months. The overall SIRR was 2.46 (95% CI, 2.21-2.74), and the overall SIRD was 4.11 (95% CI, 3.37-4.85) strokes per 1000 person-years (PY). The cumulative incidence of stroke was 3% at 5 years and 7% at 10 years after HNC diagnosis. The SIRR was highest among individuals diagnosed at younger than 40 years (SIRR, 30.55 [95% CI, 16.24-52.35]). All population subsets defined by age, sex, race and ethnicity, HNC subsites (except tongue), stage, histology, and treatment modalities had increased risk of stroke compared with the general population. The SIRR and SIRD were significantly higher among individuals who had a primary radiation treatment approach (SIRR, 3.01 [95% CI, 2.64-3.43]; SIRD, 5.12 [95% CI, 4.18-6.29] strokes per 1000 PY) compared with a primary surgery approach (SIRR, 1.64 [95% CI, 1.31-2.05]; SIRD, 1.84 [95% CI, 0.923.67] strokes per 1000 PY). Conclusions and Relevance: In this cross-sectional study of survivors of HNC, elevated stroke risks were observed across different age, subsites, and treatment modalities, underscoring the importance of early screening and intervention.

Indirect Treatment Comparison of First-Line CDK4/6-Inhibitors in Post-Menopausal Patients with HR+/HER2- Metastatic Breast Cancer.

Background: CDK4/6-inhibitors have demonstrated similar efficacy and are considered an effective first-line endocrine treatment of patients with hormone-receptor positive (HR+)/human-epidermal-growth-factor-receptor-2 negative (HER2-) metastatic breast cancer (MBC) in the endpoint of progression-free survival (PFS). Amongst these, palbociclib was first to achieve regulatory approval, followed subsequently by ribociclib and abemaciclib. However, recent updates of overall survival (OS) showed inconsistencies in the OS benefit for palbociclib compared with the other two CDK4/6-inhibitors. With the lack of head-to-head comparison studies, our study sought to compare indirect survival outcomes between CDK4/6-inhibitors in this setting using a novel reconstructive algorithm. Methods: Phase III randomized trials comparing first-line aromatase inhibitor with/without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2- MBC were identified through systemic review and literature search of online archives of published manuscripts and conference proceedings. A graphical reconstructive algorithm was utilized to retrieve time-to-event data from reported Kaplan-Meier OS and PFS plots to allow for comparison of survival outcomes. Survival analyses were conducted with Cox proportional-hazards model with a shared-frailty term. Results: Three randomized phase III trials-PALOMA-2, MONALEESA-2 and MONARCH-3-comprising 1827 patients were included. Indirect pairwise comparisons of all CDK4/6-inhibitors showed no significant PFS differences (all p > 0.05). Likewise, indirect treatment comparison between ribociclib vs. palbociclib (one-stage: HR = 0.903, 95%-CI: 0.746-1.094, p = 0.297), abemaciclib vs. palbociclib (one-stage: HR = 0.843, 95%-CI: 0.690-1.030, p = 0.094) and abemaciclib vs. ribociclib (one-stage: HR = 0.933, 95%-CI: 0.753-1.157, p = 0.528) failed to demonstrate a significant OS difference. Conclusions: Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitors in post-menopausal patients with HR+/HER2- MBC.

Radiation Oncology Research in Asia: Current Status and a Peep Into the Future From the Federation of Asian Organizations for Radiation Oncology.

PURPOSE: This survey was conducted to assess the current research practices among the 14 members of the Federation of Asian Organizations for Radiation Oncology (FARO) committee, to inform measures for research capacity building in these nations. MATERIALS AND METHODS: A 19-item electronic survey was sent to two research committee members from the 14 representative national radiation oncology organizations (N = 28) that are a part of FARO. RESULTS: Thirteen of the 14 member organizations (93%) and 20 of 28 members (71.5%) responded to the questionnaire. Only 50% of the members stated that an active research environment existed in their country. Retrospective audits (80%) and observational studies (75%) were the most common type of research conducted in these centers. Lack of time (80%), lack of funding (75%), and limited training in research methodology (40%) were cited as the most common hindrances in conducting research. To promote research initiatives in the collaborative setting, 95% of the members agreed to the creation of site-specific groups, with head and neck (45%) and gynecological cancers (25%) being the most preferred disease sites. Projects focused on advanced external beam radiotherapy implementation (40%), and cost-effectiveness studies (35%) were cited as some of the potential areas for future collaboration. On the basis of the survey results, after result discussion and the FARO officers meeting, an action plan for the research committee has been created. CONCLUSION: The results from the survey and the initial policy structure may allow facilitation of radiation oncology research in the collaborative setting. Centralization of research activities, funding support, and research-directed training are underway to help foster a successful research environment in the FARO region.

Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma: A Meta-analysis Including Low PD-L1 Subgroups.

Importance: Immune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced esophageal squamous cell carcinoma in both first- and second-line settings. However, the benefit of ICIs in patients with low programmed death ligand 1 (PD-L1) expression remains unclear. Objective: To derive survival data for patient subgroups with low PD-L1 expression from clinical trials comparing ICIs with chemotherapy in esophageal squamous cell carcinoma and to perform a pooled analysis. Data Sources: Kaplan-Meier curves from the randomized clinical trials were extracted after a systematic search of Scopus, Embase, PubMed, and Web of Science from inception until October 1, 2021. Study Selection: Randomized clinical trials that investigated the effectiveness of anti-PD-1-based regimens for advanced esophageal squamous cell carcinoma and that reported overall survival (OS), progression-free survival, or duration of response were included in this meta-analysis. Data Extraction and Synthesis: Kaplan-Meier curves of all-comer populations, subgroups with high PD-L1, and those with low PD-L1 (when available) were extracted from published articles. A graphic reconstructive algorithm was used to calculate time-to-event outcomes from these curves. In studies with unreported curves for subgroups with low PD-L1 expression, KMSubtraction was used to impute survival data. KMSubtraction is a workflow to derive unreported subgroup survival data with from subgroups. An individual patient data pooled analysis including previously reported and newly imputed subgroups was conducted for trials with the same treatment line and PD-L1 scoring system. Data analysis was conducted from January 1, 2022, to June 30, 2022. Main Outcomes and Measures: Primary outcomes included Kaplan-Meier curves and hazard ratios (HRs) for OS for subgroups with low PD-L1 expression. Secondary outcomes included progression-free survival and duration of response. Results: The randomized clinical trials CheckMate-648, ESCORT-1st, KEYNOTE-590, ORIENT-15, KEYNOTE-181, ESCORT, RATIONALE-302, ATTRACTION-3, and ORIENT-2 were included, totaling 4752 patients. In the pooled analysis of first-line trials that evaluated a tumor proportion score (CheckMate-648 and ESCORT-1st), no significant benefit in OS was observed with immunochemotherapy compared with chemotherapy in the subgroup of patients who had a tumor proportion score lower than 1% (HR, 0.91; 95% CI, 0.74-1.12; P = .38) compared with chemotherapy. In the pooled analysis of first-line trials that evaluated combined positive score (KEYNOTE-590 and ORIENT-15), there was a significant but modest OS benefit for immunochemotherapy compared with chemotherapy in the subgroup with a combined positive score lower than 10 (HR, 0.77; 95% CI, 0.62-0.94; P = .01). Conclusions and Relevance: Findings suggest a lack of survival benefit of ICI-based regimens in the first-line setting compared with chemotherapy alone in the subgroup with a tumor proportion score lower than 1%.

Outcomes of Patients With Spinal Metastases From Prostate Cancer Treated With Conventionally-Fractionated External Beam Radiation Therapy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the outcomes of conventionally-fractionated external beam radiation therapy (cEBRT) in the treatment of prostate cancer spinal metastases (PCSM). METHODS: Patients who received palliative cEBRT for PCSM in our institution between 2008 and 2018 were included. Our outcomes were local progression-free survival (LPFS), overall survival (OS), pain response and toxicities graded using CTCAE version 4.03. Univariable and multivariable Cox proportional hazard regressions were performed to identify predictors for LPFS and OS. RESULTS: A total of 100 patients with 132 sites of PCSM were identified, with a median follow-up of 54 months. Fourteen-percent of patients underwent surgical intervention before receiving cEBRT. Eighteen spinal segments (13.6%) had local progression, with a median time to local progression of 8 months. The median LPFS and OS were 7.8 and 9.0 months, respectively. The complete and partial pain response rates were 57% and 39% respectively. The incidence of grade ≥3 acute toxicities was 11%. Better ECOG performance status (0 to 1), castration-sensitive disease, spinal surgery and use of novel antiandrogen agent were identified as significant predictors for improved OS on multivariable analysis. CONCLUSIONS: In our prostate cancer cohort, cEBRT is an effective treatment modality for local palliation of spinal metastases. More aggressive treatment approach should be considered for patients with excellent performance status and castration-sensitive disease in light of their expected longer survival. Further studies are warranted to identify the predictors for radiotherapy response in this population.

Quantifying the changes in the tumour vascular micro-environment in spinal metastases treated with stereotactic body radiotherapy - a single arm prospective study.

BACKGROUND: The primary objective was to quantify changes in vascular micro-environment in spinal metastases (SM) patients treated with stereotactic body radiotherapy (SBRT) with multi-parametric dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). The secondary objective was to study plasma biomarkers related to endothelial apoptosis. PATIENTS AND METHODS: Patients were imaged with DCE-MRI at baseline/1-week/12-weeks post-SBRT. Metrics including normalised time-dependent leakage (Ktrans), permeability surface product (PS), fractional plasma volume (Vp), extracellular volume (Ve) and perfusion (F) were estimated using distributed parameter model. Serum acid sphingomyelinase (ASM) and sphingosine-1-phosphate (S1P) were quantified using ELISA. Clinical outcomes including physician-scored and patient-reported toxicity were collected. RESULTS: Twelve patients (with varying primary histology) were recruited, of whom 10 underwent SBRT. Nine patients (with 10 lesions) completed all 3 imaging assessment timepoints. One patient died due to pneumonia (unrelated) before follow-up scans were performed. Median SBRT dose was 27 Gy (range: 24-27) over 3 fractions (range: 2-3). Median follow-up for alive patients was 42-months (range: 22.3-54.3), with local control rate of 90% and one grade 2 or higher toxicity (vertebral compression fracture). In general, we found an overall trend of reduction at 12-weeks in all parameters (Ktrans/PS/Vp/Ve/F). Ktrans and PS showed a reduction as early as 1-week. Ve/Vp/F exhibited a slight rise 1-week post-SBRT before reducing below the baseline value. There were no significant changes, post-SBRT, in plasma biomarkers (ASM/S1P). CONCLUSIONS: Tumour vascular micro-environment (measured by various metrics) showed a general trend towards downregulation post-SBRT. It is likely that vascular-mediated cell killing contributes to excellent local control rates seen with SBRT. Future studies should evaluate the effect of SBRT on primary-specific spinal metastases (e.g., renal cell carcinoma).

Use of the Cancer and Aging Research Group Predictive Model for Chemotherapy-Related Toxic Effects in a Multiethnic, Older Adult Asian Population.

Importance: The Cancer and Aging Research Group (CARG) prediction model for chemotherapy-related toxic effects has been developed but not yet validated in older Asian adults. In view of differences in drug metabolism and toxic effect reporting in the Asian population, the ability of this tool to guide the cancer treatment decision-making process in older Asian adults needs to be assessed. Objective: To examine the validity of the CARG predictive model in a multiethnic Asian cohort of older adults. Design, Setting, and Participants: In this prognostic study, patients of various Asian ethnicities 70 years or older with a solid tumor diagnosis receiving chemotherapy at the National University Cancer Institute, Singapore, were accrued from June 1, 2017, to January 1, 2019. Their risks of chemotherapy-related toxic effects were calculated using the CARG tool. A geriatric assessment was performed, and the treating oncologist (blinded to the CARG scores) was asked to give an estimated likelihood of toxic effects (low, medium, or high). Chemotherapy-related toxic effects were recorded during each clinic visit. Validation of the prediction model was performed by calculating the area under the receiver operating characteristic curve. Multivariate analyses were performed to identify variables in other domains in the geriatric assessment predicting for severe toxic effects. Main Outcomes and Measures: Grade 3 to 5 toxic effects and hospitalization. Results: The study included 200 patients (median age, 74 years [range, 70-89 years]; 110 [55.0%] male; 177 [88.5%] Chinese, 17 [8.5%] Malay, 4 [2.0%] Indian, and 2 [1.0%] other ethnicities [according to Singapore's national system of race classification]). A total of 137 patients (68.5%) experienced grade 3 to 5 toxic effects, and 131 (65.5%) required hospitalization. The area under the receiver operating characteristic curve for the CARG chemotoxicity prediction model was 0.74 (95% CI, 0.67-0.82), retaining good discrimination in the study population. Conclusions and Relevance: This prognostic study conducted in a multiethnic Asian cohort of older adults supports the validity of the CARG predictive model in this population, predicting which older adults are at risk of chemotherapy-related toxic effects.

Stereotactic body radiation therapy versus conventional external beam radiation therapy for painful bone metastases: A systematic review and meta-analysis of randomized trials.

PURPOSE: To compare the efficacy and safety of stereotactic body radiation therapy (SBRT) and conventional external beam radiation therapy (cEBRT) in patients with previously unirradiated painful bone metastases (BM). METHODS: We searched biomedical databases for eligible randomized controlled trials (RCTs). The outcomes of interest were pain response, local progression, overall survival (OS) and adverse events. We used established tools to assess the quality of the individual trials and certainty of the pooled evidence. We performed meta-analyses using random effects models. RESULTS: Six RCTs were identified. SBRT improved complete pain response rates at 3 months (OR, 3.38; 95% CI, 1.88-6.07; high certainty), reduced local progression rates (OR, 0.19; 95% CI, 0.06-0.62; high certainty) and increased pain flare rates. There were no differences for other outcomes. CONCLUSION: Among patients with previously unirradiated painful BM, SBRT significantly improved complete pain response rates at 3 months, delayed local progression and increased pain flare rates.

Booster doses of COVID-19 vaccines for patients with haematological and solid cancer: a systematic review and individual patient data meta-analysis.

IMPORTANCE: Patients with cancer have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies. OBJECTIVE: To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose. METHODS: PubMed, EMBASE, CENTRAL and medRxiv were searched from 1st January 2021 to 10th March 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: After the eligibility assessment, 22 studies were included in this systematic review and 17 for meta-analysis of seroconversion in non-responders, pooling a total of 849 patients with haematological cancer and 82 patients with solid cancer. Haematological cancer non-responders exhibited lower seroconversion at 44% (95% CI 36-53%) than solid cancer at 80% (95% CI 69-87%). Individual patient data meta-analysis found the odds of having a meaningful rise in antibody titres to be significantly associated with increased duration between the second and third dose (OR 1.02, 95% CI 1.00-1.03, P ≤ 0.05), age of patient (OR 0.960, 95% CI 0.934-0.987, P ≤ 0.05) and cancer type. With patients with haematological cancer as a reference, patients with lung cancer had 16.8 times the odds of achieving a meaningful increase in antibody titres (OR 16.8, 95% CI 2.95-318, P ≤ 0.05) and gastrointestinal cancer patients had 25.4 times the odds of achieving a meaningful increase in antibody titres (OR 25.4, 95% CI 5.26-492.21, P ≤ 0.05). CONCLUSIONS: administration of a COVID-19 vaccine booster dose is effective in improving seroconversion and antibody levels. Patients with haematological cancer consistently demonstrate poorer response to booster vaccines than patients with solid cancer.

Survival rates and safety associated with chemoradiotherapy followed by surgery and chemoradiotherapy alone for patients with T4 esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: The optimal treatment approach for T4 esophageal cancer is not well established. We aimed to perform a systematic review and meta-analysis to determine the survival rates and safety of chemoradiotherapy followed by surgery (CRT-S) and chemoradiotherapy alone (CRT) in patients with T4 Nany M0 esophageal cancer. MATERIALS AND METHODS: We searched databases for eligible prospective or retrospective studies. The outcomes of interest were overall survival (OS) at 1, 3 and 5 years, treatment-related fistula formation and mortality rates. Meta-analyses were performed using the random effects models separately for studies evaluating CRT-S and CRT. Subgroup analyses were performed based on histology, radiation dose, chemotherapy regimen and duration of the interval between CRT and surgery. RESULTS: We identified 23 studies including 1,119 patients with predominantly squamous cell carcinoma (93%) and adenocarcinoma (3%) histology. The OS rates of patients receiving CRT-S were 65%, 36% and 20% at 1, 3 and 5 years, respectively. The OS rates of patients receiving CRT were 30%, 11% and 10% at 1, 3 and 5 years, respectively. Treatment-related fistula formation rates were 4% for CRT-S and 9% for CRT. Treatment-related mortality rates were 3% for both groups. Subgroup analyses showed that the interval of >2 months between CRT and surgery was associated with significantly improved OS rates at 1, 3 and 5 years. CONCLUSION: Chemoradiotherapy is an efficacious treatment approach for T4 esophageal cancer, with clinically acceptable rates of treatment-related fistula formation and mortality. Tri-modality approach with surgery can be considered in carefully selected patients. Our study findings should be interpreted with caution due to the lack of high-quality evidence. Randomized controlled trials are warranted to confirm these findings.

Risk of Stroke in Nasopharyngeal Cancer Survivors: A National Registry-Based Population Cohort Study.

BACKGROUND AND OBJECTIVES: We aim to determine the risk of stroke and death within 30 days after stroke in nasopharyngeal cancer (NPC) survivors. METHODS: We conducted a population-based cohort study of patients diagnosed with NPC from January 1, 2005, to December 31, 2017. Using the cancer and stroke disease registries and the Singapore general population as the reference population, we report the age-standardized incidence rate differences (SIRDs) ratios (SIRs) and the cumulative incidence of stroke and the standardized mortality rate differences (SMRDs) and ratios (SMRs) for all causes of death within 30 days after stroke for NPC survivors. RESULTS: At a median follow-up of 48.4 months (interquartile range 19.8-92.9 months) for 3,849 patients diagnosed with NPC, 96 patients developed stroke. The overall SIRD and SIR for stroke were 3.12 (95% confidence interval [CI] 2.09-4.15) and 2.54 (95% CI 2.08-3.10), respectively. The SIRD was highest for the age group 70 to 79 years old (8.84 cases per 1,000 person-years, 95% CI 0.46-17.21), while the SIR was highest for the age group 30 to 39 years old (16.41, 95% CI 6.01-35.82). The SIRD and SIR for stage 1 disease were (6.96 cases per 1000 person-years, 95% CI 2.16-11.77) and (4.15, 95% CI 2.46-7.00), respectively. The SMRD and SMR for all cause deaths within 30 days of stroke were (3.20 cases per 100 persons, 95% CI -3.87 to 10.28) and (1.34, 95% CI 0.76-2.37), respectively. DISCUSSION: The overall risk of stroke was markedly elevated in survivors of NPC, especially in stage 1 disease, compared to the general population. The risk of death within 30 days of stroke was not significantly higher for NPC survivors. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence of the increased risk of stroke in survivors of NPC compared to the general population.

Outcomes of oesophageal cancer treated with neoadjuvant compared with definitive chemoradiotherapy.

INTRODUCTION: We report outcomes of patients with oesophageal cancer treated with neoadjuvant chemoradiotherapy (NACRT) plus surgery or definitive chemoradiotherapy (chemoRT) at our institution. METHODS: We retrospectively reviewed patients who underwent chemoRT from 2005 to 2017. The primary outcome was overall survival (OS). Secondary outcomes were disease-free survival (DFS) and toxicities. RESULTS: We identified 96 patients with median age of 64 years and squamous cell carcinoma in 82.3%. Twenty-nine patients (30.2%) received NACRT plus surgery, 67 patients (69.8%) received definitive chemoRT. Median follow-up was 13.5 months. The 3/5-year OS were 26.4%/13.4%, and 59.6%/51.6% in the definitive chemoRT and NACRT plus surgery groups, respectively. The 3/5-year DFS were 19.3%/12.3%, and 55.7%/37.2% in the definitive chemoRT and NACRT plus surgery groups, respectively. NACRT plus surgery significantly improved OS (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.22-0.72, P<0.01) and DFS (subhazard ratio [SHR] 5.21, 95 CI 1.20-22.7, P=0.03). Multivariable analysis for OS in the definitive chemoRT group indicated stage (1-2 vs 3-4a; HR 2.17, 95% CI 1.15-4.11, P=0.02) and feeding tube (no tube versus tube; HR 1.85, 95% CI 1.00-3.43, P=0.05) as significantly associated with OS. The cumulative incidence of local recurrence was significantly higher in the definitive chemoRT group (SHR 5.21, 95 CI 1.2022.7, P=0.03). Nineteen patients (65.5%) had postoperative complications. CONCLUSION: NACRT plus surgery improved OS and DFS. However, in view of treatment-related complications, careful selection of patients is warranted. With the predominant histology of our cohort being squamous cell carcinoma (SCC), our results may be more relevant for those with SCC.

Radiation oncology training in Singapore - A non-Australasian RANZCR training site.

The Radiation Oncology Department at The National Cancer Institute, Singapore (NCIS) and the Royal Australian and New Zealand College of Radiology (RANZCR) has had a well-established relationship that began as a partnership to grow a pool of local radiation oncologists to meet a nation's demand for radiotherapy services. This journey has surpassed its initial aims and now has produced a generation of radiation oncologists leading a national cancer institute. We recount the history and progress of this partnership here, as well as the unique success of its product; the only RANZCR-accredited radiation oncology training site outside of Australia and New Zealand since 2002. We outline the mutual benefits through many years of collaboration and deliberate efforts to grow the partnership. We also outline the distinctive specialist training path that our trainees take to meet both the local accreditation body as well as the RANZCR requirements.

Prophylactic irradiation of tracts in patients with malignant pleural mesothelioma: A systematic review and meta-analysis of randomized trials.

INTRODUCTION: The role of prophylactic irradiation of tracts (PIT) to prevent tumor seeding at the site of a diagnostic or therapeutic intervention in patients with malignant pleural mesothelioma (MPM) is controversial. This study aimed to determine the efficacy of PITs in preventing procedure tract metastases (PTM) after a chest wall procedure in MPM. MATERIALS AND METHODS: We searched various databases from inception date to April 2020 for randomized controlled trials (RCTs) comparing PIT with no PIT in patients who had a chest wall procedure for MPM. We assessed the risk of bias of individual RCT using the RoB2 tool. The primary outcome was the occurrence of PTM. Meta-analysis was performed using random-effects model. We employed the GRADE approach to assess the certainty of the evidence. RESULTS: We identified five RCTs including 737 patients. Two RCTs had a low risk of bias. PIT was associated with a significant reduction in the odds of PTM (odd ratio, 0.55; 95 % confidence interval, 0.32 to 0.95; P-value = 0.03; I2 = 13 %; GRADE: moderate certainty). One RCT reported no difference in overall survival outcome with the use of PIT. None of the RCTs performed subgroup analyses. Sensitivity analyses showed similar results when limited to RCTs with low risk of bias. CONCLUSION: PIT significantly reduces the occurrence of PTM in patients with MPM who had a diagnostic or therapeutic chest wall procedure.

Palliative radiotherapy for bladder cancer: a systematic review and meta-analysis.

BACKGROUND/PURPOSE: The optimal dose fractionation for palliative radiotherapy (RT) in patients with symptomatic advanced bladder cancer is unclear. This study aimed to determine if a higher dose of RT was associated with improved symptoms response rates. METHODS: We searched PubMed, Central and Embase for eligible studies published from 1990 to 2019. The primary outcomes were symptoms response rates for hematuria, dysuria and frequency. Secondary outcomes included treatment-related adverse events and quality of life. RESULTS: We found one randomized, four prospective and eight retrospective non-comparative observational studies including 1320 patients who received palliative bladder radiotherapy for symptom relief. The dose fractionation schedules varied across studies ranging from 8 Gy single fraction to 60 Gy in 2 to 8 Gy per fraction. The pooled response rates for hematuria, dyuria and frequency symptoms were 74%, 58% and 71% respectively. A higher dose of RT was not associated with improved response rates of hematuria and frequency. However, a higher dose of RT was associated with a longer duration of hematuria response and reduced response of dysuria. Grade 3 gastrointestinal and genitourinary toxicity occurred in up to 26% of patients. Health-related quality of life (HRQOL) outcomes were reported in one study. CONCLUSION: This systematic review demonstrates that a higher dose of bladder RT was not associated with improved response rates of hematuria and frequency symptoms but was associated with reduced response of dysuria. Higher doses of bladder RT was associated with more durable hematuria response. Prospective studies to determine the effects of palliative bladder radiotherapy on HRQOL outcomes are warranted.

Quality of reporting of cranial irradiation techniques in randomized controlled trials of primary brain tumors: A systematic review.

BACKGROUND: To assess the quality of reporting of cranial irradiation (CR) techniques in randomized controlled trials (RCTs) of primary brain tumors. METHODS: We searched PubMed and EMBASE for RCTs of primary brain tumors, published from January 1999 to November 2019 which included CR as one of the intervention arms. We assessed the initial RCTs report on whether they reported the prespecified ten criteria for CR technique adequately. Multivariable logistic regression was performed to determine the factors that were predictive of adequate quality of reporting. RESULTS: We found 85 eligible trial reports. There was significant variability in the quality of reporting among the included studies. Total radiotherapy (RT) dose and fractionation schedule were reported adequately in more than 90% of the included trials. The organs at risk dose constraints, treatment verification procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in less than 30% of included trials. Twenty-three trials (27%) reported seven criteria or more adequately. Multivariable analysis showed that trials conducted by cooperative groups, published RT quality assurance results and having a low risk of bias in the methodological quality have higher odds of having adequate quality in reporting of CR technique (judged as adequate reporting in seven criteria or more). CONCLUSIONS: The quality of reporting on CR techniques in the RCTs of primary brain tumors is variable and suboptimal. Guidelines should be introduced to improve clarity and ensure consistency in the quality of reporting.

Applying the ASCO and European Society for Medical Oncology Value Frameworks to Nasopharyngeal Cancer Treatments: Is Adding Induction Chemotherapy or Adjuvant Chemotherapy to Concurrent Chemoradiotherapy Worthwhile?

PURPOSE: To determine and compare the incremental clinical benefit (ICB) and costs of induction chemotherapy (IC) when added to concurrent chemoradiotherapy (CCRT), concurrent chemotherapy (CC) when added to radiotherapy (RT), and CC plus adjuvant chemotherapy (AC) when added to RT for locally advanced nasopharyngeal cancer (LA-NPC). MATERIALS AND METHODS: We searched phase III randomized controlled trials (RCTs) that reported overall survival benefit with the use of IC, CC, and CC + AC in LA-NPC. We quantified the ICB using the ASCO and European Society for Medical Oncology (ESMO) value frameworks. We calculated the incremental drug costs in US dollars using the lowest average wholesale price reported in the Lexicomp drug database. RESULTS: We identified three RCTs on IC, three RCTs on CC, and four RCTs on CC + AC. The ICB was judged to be grade A based on the ESMO framework. The ASCO Net Health Benefit score ranged from 17.43 to 57.39. The incremental drug costs ranged from $133.46 to $626.14. There were no statistically significant differences in the mean Net Health Benefit scores (39.37 for IC v 37.61 for CC v 33.98 for CC + AC; P = .89) and costs ($383 for IC v $253 for CC v $460 for CC + AC; P = .27) between the three approaches. There was no statistically significant correlation between ICB and costs. CONCLUSION: The magnitudes of ICB and incremental drug costs of adding of IC to CCRT, CC to RT, and CC + AC to RT for LA-NPC are not significantly different.

Impact of programmed death-ligand 1 expression on the patients of stage IV non-small cell lung cancer harboring epidermal growth factor receptor mutation: a systematic review and meta-analysis.

BACKGROUND: To determine the impact of programed death-ligand 1 (PD-L1) expression on progression-free survival (PFS) outcomes in stage IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with first-line EGFR tyrosine kinase inhibitors (TKIs). MATERIAL AND METHODS: We searched biomedical databases for studies comparing PFS outcomes of PD-L1-positive versus (vs) PD-L1-negative tumors. We assessed the methodological quality of eligible studies using ROBINS-I tool. We employed a two-staged meta-analysis approach by reconstructing individual patient data of each study from the published Kaplan-Meier curves and then pooling the individual hazard ratios (HRs) and weighted mean differences (WMDs) for restricted mean PFS time at 6 (RMPFST6) and 12 (RMPFST12) months using random-effect models. We assessed the quality of summarized evidence using GRADE approach. RESULTS: We identified five non-randomized comparative studies including 435 patients. The overall risk of bias in the methodological quality of included studies was moderate. PD-L1-positive tumors were associated with significantly worse PFS outcomes compared to PD-L1-negative tumors (HR: 2.41, 95% confidence interval (CI): 1.59-3.66, p < .001; WMD in RMPFST6: -1.01, 95% CI: -1.65 to -0.37, p = .002; WMD in RMPFST12: -2.64, 95% CI: -4.40 to -0.88, p = .003). Subgroup analysis showed that the effect of PD-L1 expression on PFS outcomes was greater for studies using older-generation rather than third-generation TKIs (HR: 2.69 vs 1.22, p = .069; WMD in RMPFST6: -1.23 vs -0.07, p = .005; WMD in RMPFST12: -3.29 vs -0.12, p = .003). The quality of summarized evidence was judged to be low. CONCLUSION: There is low certainty in the evidence to suggest that positive PD-L1 expression is associated with inferior disease control and survival outcomes in patients with stage IV EGFR-mutated NSCLC treated with first-line EGFR TKIs.

T4 cervical esophageal cancer cured with modern chemoradiotherapy: A case report.

BACKGROUND: T4 esophageal cancer portends a poor prognosis, particularly when it is complicated by a tracheoesophageal fistula (TEF) either resulting from disease or occurring as a complication of treatment. Patients with TEF that occurs during treatment are commonly treated with palliative intent because fistula-associated treatment complications such as aspiration pneumonia and mediastinitis are associated with high morbidity and mortality. To date, there is no clear evidence on the optimal treatment of T4 esophageal cancer, particularly when a TEF formation occurs. CASE SUMMARY: A 67-year-old gentleman who presented with dysphagia and weight loss. Endoscopy and imaging revealed a T4N1M0 cervical esophageal squamous cell carcinoma. He received image-guided intensity-modulated radiation therapy, with concurrent weekly carboplatin (area under curve 2 mg/mL per minute) and paclitaxel (50 mg/m2 of body surface area). One week after treatment initiation (16.2 Gy thus far), he developed cough on swallowing. A TEF was detected on image-guided radiation therapy using cone-beam computed tomography during the treatment course, for which a tracheal stent was inserted. After discussing the risks and morbidity of continuing treatment, he resumed chemoradiotherapy with an additional radiation dose of 45 Gy in 25 fractions. Three months after completion of chemoradiotherapy, he developed an esophageal stricture that required esophageal stenting and dilatation. The patient remains cancer-free at two year on follow-up. Complete response of esophageal cancer was evident on post-treatment endoscopy and computed tomography imaging, with successful closure of TEF. CONCLUSION: This case highlights that successful curative treatment for esophageal cancer complicated by a TEF is possible using novel chemotherapeutic regimens and modern radiation technologies.