Prediction model for short-term mortality after palliative radiotherapy for patients having advanced cancer: a cohort study from routine electronic medical data.

We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5-69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47-2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52-1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79-0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81, P = 0.094), providing an accurate prediction for almost all 30-day mortality probabilities. The predictive scoring system accurately predicted 30-day mortality among patients with stage IV cancer. Oncologists may use this to tailor palliative therapy for patients.

A retrospective review for the use of palliative sedation in a regional hospital in Hong Kong.

BACKGROUND: Palliative sedation is defined as monitored use of medication intended to induce a state of decreased or absent awareness to relieve intractable suffering in a manner that is ethically acceptable to the patient, family, and health-care providers. The prevalence of palliative sedation reported ranges from 10% to 50% during in end of life care setting. There was no major review performed on the prevalence and practice of palliative sedation in Hong Kong. Besides, published guidelines and medication recommendations are developed in Caucasian settings, which may not be taken into account the cultural aspect in Chinese. Therefore, we would like to review our practice in caring terminal cancer patients to report the prevalence and practice of palliative sedation and to review factors associated with successful sedation in this group of patients. METHODS: One-hundred and eighty consecutive patients with histological or radiological evidence of malignancy who died in palliative care ward from 1st July to 30th September 2017 were screened. All patients who received continuous midazolam infusion were included. Patients' demographic data, cancer disease status, laboratory results and interview records were retrieved from electronic patient records and in-patient hospital notes. The reason for sedation, background and concurrent symptoms during sedation, and the clinical notes on symptom control during the sedation period were all reviewed. All the drug records including the dose of midazolam and other concomitant drugs, duration of palliative sedation as well as the depth of sedation were assessed. Survival data estimated from the day of admission to our department until death were recorded. RESULTS: Three hundred and thirty-nine patient-days, contributed by 81 patients out of 180 patients (45%), with midazolam infusion were studied. There was no statistical difference in the baseline characteristics of both patient groups. Median survival since admission to oncology ward in the sedated group was 11 versus 9 days in the non-sedated group (P=0.65). The median time for patients on sedation was 32.33 hours (range, 2.91-1,240 hours). Dyspnea was the most common cause of palliative sedation (78.0%), followed by delirium (40.9%). The mean dose of midazolam infusion was 10 milligram per day (range, 5-45 mg). Deranged liver function was the only statistically significant factor associated with successful sedation after multivariate analysis. CONCLUSIONS: The use of palliative sedation is safe and effective in managing refractory symptoms and is not associated with worsening of survival. Deranged liver function was associated with better symptom control. The dose of midazolam and haloperidol needed for adequate symptom control were lower than suggested in Western guidelines. Further studies on the dose requirement in Chinese population are warranted. Establishing consensus and guidelines on palliative sedation in Hong Kong should be the way forward to ensure quality care to this group of patients.

The Value of Prognostic Nutritional Index in Follicular Lymphoma.

OBJECTIVES: Previous studies reported that prognostic nutritional index (PNI), a marker of host inflammatory and nutritional status, is associated with prognoses in a number of cancer types. Thus, we investigated PNI at diagnosis as a prognostic factor in FL. METHODS: We reviewed FL patients in Tuen Mun Hospital, Hong Kong from 2000 to 2014 (n=88). PNI was calculated by serum albumin (g/L)+5×absolute lymphocyte count (10/L). We determined the best PNI cut-off value using receiver-operating characteristic curves. The extent to which progression-free survival (PFS) and overall survival differed by PNI cut-off was assessed using Kaplan-Meier and log-rank tests. Cox proportional hazards model was utilized to adjust for covariates. RESULTS: The best cut-off value for PNI was determined to be 45. Patients with high PNI (>45) had a higher complete response (CR) rate after primary treatment, 46 of 61 (75.4%) patients with high PNI had CR, compared with 10 of 23 (43.5%) for low PNI (2-sample test of proportions P-value=0.006). Further, higher PNI at relapse as a continuous variable was associated with superior postprogression survival with a hazard ratio (HR) 0.88 (95% confidence interval [CI], 0.81-0.96). In multivariate analysis, high PNI at diagnosis had superior PFS (adjusted HR of 0.37; 95% CI, 0.15-0.93). CONCLUSIONS: PNI was shown to be independent prognostic factor of PFS in FL. It is a cheap and widely available biomarker. Future study is needed to validate its prognostic value and clinical utility in a prospective cohort.

Outcome of neoadjuvant chemoradiation in MRI staged locally advanced rectal cancer: Retrospective analysis of 123 Chinese patients.

BACKGROUND: For advanced rectal cancer with involved or threatened mesorectal fascia (MRF), current standard is pre-operative long course chemoradiotherapy (PLCRT) with either capecitabine or 5-fluorouracil (5-FU). However, few Chinese data on its clinical outcome are available, especially for those with pelvic MRI staging. METHODS: Between Jan-2009 and Oct-2014, 123 consecutive patients with biopsy proven adenocarcinoma of rectum, all with pelvic MRI staging, selected for PLCRT after multi-disciplinary team discussion were recruited. Their clinical records were retrospectively reviewed. RESULTS: Median follow-up was 1392 days (range: 48-2886) MRI defined poor risk factors as follows: MRF threatened or involved ≤1 mm 61.8% (n = 76), cT4 13.8% (n = 17), cN2 26.8% (n = 33) and low-lying tumor (≤5 cm from anal verge) 24.4% (n = 30). Five year OS and DFS were 63.9% and 68.3% respectively. Among 112 patients who received TME, 108 (96.4%) had microscopic clear resection (R0). Twelve and 32 individuals had pathological complete response and ypT0-2N0, respectively. Five local recurrences (4.5%) were detected. The incidence of grade 3 or above acute and late radiotherapy toxicity was 8.1% and 12.2% respectively. After multivariate adjustment, positive circumferential resection margin (CRM) status on pathology report was found to be significant factor for worse OS and DFS. CONCLUSION: The clinical outcomes of PLCRT in our institution are comparable with those in western literature. Our MRI staging lends support to the validity of data. CRM status is the most significant prognostic factor in OS and DFS, after multivariate adjustment.

The Role of Radiotherapy in Early-stage Primary Diffuse Large B-Cell Lymphoma of the Waldeyer Ring: A Retrospective Cohort Study.

OBJECTIVES: The role of radiotherapy (RT) in improving survival of patients with diffuse large B-cell lymphoma (DLBCL) of the Waldeyer ring (WR) remains controversial. Therefore, this retrospective cohort study aimed to determine the role of RT in the treatment of DLBCL of the WR as well as the effects of associated covariates. MATERIALS AND METHODS: Patients (n=35) with stage I to II DLBCL of the WR who underwent treatment at our center between 1994 and 2010 were retrospectively investigated. All patients had histologic diagnosis and staging workup completed. Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were analyzed. Variables with a P-value of <0.1 were subjected to multivariate Cox proportional hazards model analyses. RESULTS: The median OS was 8.1 years. The 5-year OS, DFS, and EFS rates were 59.4%, 53.8%, and 70.7%, respectively; the corresponding 10-year rates were 34.9%, 29.5%, and 51.0%, respectively. The 5-year OS rate was significantly higher in the RT group than in the non-RT group (65.4% vs. 36.4%, respectively; P=0.008). On multivariate analysis, RT was associated with improved OS (hazard ratio=0.15; 95% confidence interval [CI], 0.04-0.50; P=0.002) and EFS (hazard ratio=0.29; 95% CI, 0.095-0.86; P=0.026). An Eastern Cooperative Oncology Group performance status >1 and age above 60 years were also found to negatively influence OS and EFS. CONCLUSIONS: RT was associated with improved OS and EFS in stage I to II DLBCL of the WR. Future prospective studies are required to confirm these findings.

Throwing the dart blind-folded: comparison of computed tomography versus magnetic resonance imaging-guided brachytherapy for cervical cancer with regard to dose received by the 'actual' targets and organs at risk.

PURPOSE: Computed tomography (CT) is inferior to magnetic resonance imaging (MRI) in cervical tumor delineation, but similar in identification of organs at risk (OAR). The trend to over-estimate high-risk and low-risk clinical target volume (HRCTV, IRCTV) on CT can lead to under-estimation of dose received by 90% (D90) of the 'actual' CTV. This study aims to evaluate whether CT-guided planning delivers adequate dose to the 'actual' targets while spares the OAR similarly. MATERIAL AND METHODS: MRI-guided high-dose-rate image-guided brachytherapy (IGBT) was performed in 11 patients. The pre-brachytherapy CTs were retrospectively contoured to generate CT-guided plans. MRI-based contours (HRCTVmri, IRCTVmri, bladdermri, rectummri, and sigmoidmri) were fused to CT plans for dosimetric comparison with MRI-guided plans. Paired 2-tailed t-test and Wilcoxon signed-rank test were used to analyze data. RESULTS: 63.6% of CT plans achieved the HRCTVmriD90 constraint (≥ 7.2 Gy in one fraction), compared with 90.9% for MRI plans. > 90% of both modalities achieved the OAR's constraints (EMBRACE). The percentage of CT and MRI plans that achieved the aims (EMBRACE II) for bladder, rectum, and sigmoid were 36.4% vs. 81.8%, 63.6% vs. 63.6%, and 72.7% vs. 72.7%, respectively. There were no statistically significant differences in HRCTVmriD90, IRCTVmriD90, or dose received by the most exposed 2 cm3 (D2cc) of OARmri between the modalities. Excluding the CT plans not achieving HRCTVmriD90 constraint, there were significant increase in bladdermriD2cc, rectummriD2cc, and sigmoidmriD2cc, compared with MRI plans (0.9 Gy/Fr, 95% CI 0.2-1.5, p = 0.018; 0.9 Gy/Fr, 95% CI 0.3-1.4, p = 0.009; 0.5 Gy/Fr, 95% CI 0.2-0.9, p = 0.027, respectively). CONCLUSIONS: MRI-based IGBT remains the gold standard. CT planning may compromise HRCTVmriD90 or increase OARmriD2cc, which could decrease local control or increase treatment toxicity.

Survival analysis of malignant epidural spinal cord compression after palliative radiotherapy using Tokuhashi scoring system and the impact of systemic therapy.

BACKGROUND: Previous studies have shown similar clinical outcomes of both single and multi-fraction (Fr) radiation therapy among malignant epidural spinal cord compression (MSCC) patients with poor prognosis; whereas, patients expected to have longer survival may require long-course radiotherapy to prevent local failure. However, such a poor prognosis risk group has not yet been clearly identified for use in daily clinical practice. We examined if the known predictive Tokuhashi scoring system could be adapted in MSCC patients treated with palliative radiation therapy. METHODS: A retrospective review of the treatment outcomes of MSCC patients who received palliative radiotherapy from January 2014 to May 2015 was conducted. The patients were stratified into two groups according to the Tokuhashi scoring system: group 1 (score <9), expected survival <6 months, and group 2 (score >8), expected survival >6 months. Their survival was tested against subsequent systemic therapy (chemotherapy, targeted or hormonal therapy) and other risk factors including age, primary site, visceral metastasis, baseline motor function, prior radiotherapy and radiotherapy fractionation (single or multiple). RESULTS: The outcomes of 119 patients were studied, 116 (97.5%) patients had already succumbed. The overall median survival was 55 days (range, 4-576 days). Ninety-three patients (78.2%) belonged to group 1. The median dose delivered was 25 Gy in 5 Frs [range, 7 Gy in 2 Frs-40 Gy in 10 Frs (to the cauda equina)]. Only nine patients (7.6%) received single-Fr radiotherapy, all belonging to Tokuhashi group 1. Patients belonging to group 1 had shorter median survival than group 2; 49 and 108 days, respectively (P=0.003). Among all the patients, subsequent systemic treatment [hazard ratio (HR) =0.407; 95% confidence interval (CI), 0.236-0.702; P=0.001], non-visceral metastasis (HR =0.608; 95% CI, 0.387-0.956; P=0.031) and primary lung or breast or prostate cancer (P=0.029) were associated with better survival in multivariate analysis. For patients in group 1, primary breast or prostate cancer (HR =0.264; 95% CI, 0.122-0.572; P=0.001) or lung cancer (HR =0.421; 95% CI, 0.246-0.719; P=0.002), non-visceral metastasis (HR =0.453; 95% CI, 0.264-0.777; P=0.004), multi-Fr (HR =0.455; 95% CI, 0.217-0.956; P=0.038) and subsequent systemic therapy (HR =0.460; 95% CI, 0.252-0.842; P=0.012) were associated with better survival. The survival of a subset of patients in group 1 without subsequent systemic therapy was dismal (median survival only 40 days) and not altered by radiotherapy schedule (P=0.189). CONCLUSIONS: MSCC comprises a very heterogenous group of patients, even under the Tokuhashi grouping. Systemic therapy or visceral metastasis may be more important prognostic factors. Further studies are necessary to better select the poor prognosis risk group. In clinical practice, single-Fr radiotherapy could be considered in Tokuhashi group 1 patients due to their expected short survival, especially for those without reasonable systemic treatment options.

Aspirin and risk of multiple myeloma in adults: A systematic review and meta-analysis.

Multiple myeloma is a relatively uncommon plasma cell malignancy. Preclinical and clinical studies have suggested that aspirin might modify the risk of multiple myeloma. We performed a systematic review and meta-analysis of studies to examine the association between regular aspirin use and risk of multiple myeloma. Five observational studies including 332,660 adults were evaluated. The pooled estimate had a hazard ratio of 0.90 (95% confidence interval =0.58-1.39; P=0.638). Odds ratios from the two case-control studies were similar. The findings demonstrated that there was no significant association between aspirin use and the risk of multiple myeloma.