Raymond Woo-Jun Jang

Simple Prognostic Model for Patients With Advanced Cancer Based on Performance Status

PURPOSE Providing survival estimates is important for decision making in oncology care. The purpose of this study was to provide survival estimates for outpatients with advanced cancer, using the Eastern Cooperative Oncology Group (ECOG), Palliative Performance Scale (PPS), and Karnofsky Performance Status (KPS) scales, and to compare their ability to predict survival. METHODS ECOG, PPS, and KPS were completed by physicians for each new patient attending the Princess Margaret Cancer Centre outpatient Oncology Palliative Care Clinic (OPCC) from April 2007 to February 2010. Survival analysis was performed using the Kaplan-Meier method. The log-rank test for trend was employed to test for differences in survival curves for each level of performance status (PS), and the concordance index (C-statistic) was used to test the predictive discriminatory ability of each PS measure. RESULTS Measures were completed for 1,655 patients. PS delineated survival well for all three scales according to the log-rank test for trend (P < .001). Survival was approximately halved for each worsening performance level. Median survival times, in days, for each ECOG level were: EGOG 0, 293; ECOG 1, 197; ECOG 2, 104; ECOG 3, 55; and ECOG 4, 25.5. Median survival times, in days, for PPS (and KPS) were: PPS/KPS 80-100, 221 (215); PPS/KPS 60 to 70, 115 (119); PPS/KPS 40 to 50, 51 (49); PPS/KPS 10 to 30, 22 (29). The C-statistic was similar for all three scales and ranged from 0.63 to 0.64. CONCLUSION We present a simple tool that uses PS alone to prognosticate in advanced cancer, and has similar discriminatory ability to more complex models.

Palliative Care and the Aggressiveness of End-of-Life Care in Patients With Advanced Pancreatic Cancer

BACKGROUND We examined the impact of palliative care (PC) on aggressiveness of end-of-life care for patients with advanced pancreatic cancer. Measures of aggressive care included chemotherapy within 14 days of death; and at least one intensive care unit (ICU) admission, more than one emergency department (ED) visit, and more than one hospitalization, all within 30 days of death. METHODS A retrospective population-based cohort study using administrative data was conducted in patients with advanced pancreatic cancer from 2005 to 2010 in Ontario, Canada. Multivariable logistic regression was performed with the above measures of aggressive care as the outcomes of interest and PC as the main exposure, adjusting for covariables. Secondary analyses examined intensity of PC as the main exposure defined in two ways: 1) absolute number of PC visits before the outcome of interest (0, 1, 2, 3+ visits) and 2) monthly rate of PC visits. RESULTS The cohort included 5381 patients (median survival 75 days); 2816 (52.3%) had received a PC consultation. PC consultation was associated with decreased use of chemotherapy near death (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.25 to 0.46); lower risk of ICU admission: OR = 0.12, 95% CI = 0.08 to 0.18; multiple ED visits: OR = 0.19, 95% CI = 0.16 to 0.23; multiple hospitalizations near death: OR = 0.24, 95% CI = 0.19 to 0.31). A per-unit increase in the monthly rate of PC visits was associated with lower odds of aggressive care for all four outcomes. CONCLUSION PC consultation and a higher intensity of PC were associated with less aggressive care near death in patients with advanced pancreatic cancer.

Quality-Adjusted Time Without Symptoms or Toxicity Analysis of Adjuvant Chemotherapy in Non–Small-Cell Lung Cancer: An Analysis of the National Cancer Institute of Canada Clinical Trials Group JBR.10 Trial

PURPOSE National Cancer Institute of Canada Clinical Trials Group JBR.10 demonstrated that adjuvant vinorelbine and cisplatin after resection of stage IB-II non-small-cell lung cancer (NSCLC) improved relapse-free and overall survival. However, many patients either are not referred for chemotherapy or decline treatment. To aid in treatment decision making, quality-adjusted survival estimates of the JBR.10 trial were derived using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis. METHODS Survival curves for treatment (N = 242) and observation groups (N = 240) were partitioned into three health states: time with >or= grade 2 (early or late) chemotherapy-related toxicity (TOX), time in relapse (REL), and time without toxicity or relapse (TWiST). Q-TWiST = u(TOX) x TOX + u(TWiST) x TWIST + u(REL) x REL, where weights u(TOX), u(TWIST), and u(REL) range from 0 to 1. Threshold utility analysis was performed to test the sensitivity of the results to changes in the weights. Weights were derived in an exploratory fashion using different methods. Methods included use of arbitrary values, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) quality-of-life data prospectively collected in JBR.10 (global assessment questions and symptom-based questions), and lastly weights European Quality of Life-Five Dimensions questionnaire collected from early-stage NSCLC (nontrial) patients after resection with discounting for toxicity and relapse. The alpha level was .05. RESULTS Threshold utility analysis revealed that adjuvant chemotherapy was preferred for all possible weight values for relapse and toxicity (u(REL), u(TOX)), although the result was not always statistically significant. The adjuvant chemotherapy group had better Q-TWiST in the range of 5 to 6 additional months, which was statistically significant using all methods. CONCLUSION Adjuvant chemotherapy in early-stage NSCLC improves quality-adjusted survival despite chemotherapy toxicity.

Derivation of utility values from European Organization for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire values in lung cancer.

Introduction: Cancer clinical trials frequently incorporate quality of life (QoL) measures but rarely patient utility. Utility information is required for cost utility evaluations of novel cancer therapies. We assessed the feasibility of converting QoL data into utility scores using the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire (EORTC QLQ-C30) and the EQ-5D in patients with non-small cell lung cancer (NSCLC). Methods: Outpatients with all different disease states of NSCLC attending a major Canadian cancer center completed the QLQ-C30 and EQ5D on a single visit. Results of the QLQ-C30 summary scores were mapped to predict EQ-5D utility scores using linear regression. Backward variable elimination using the Akaike Information Criterion was used to reduce the full model that included all QLQ-C30 summary scores to examine which QLQ-C30 dimensions best predict a patients utility score. To test the predictive power of the model, 10-fold cross-validation was used. Results: A total of 172 patients participated in the study. Median age of the sample was 66 years (range, 32–85 years); 46.5% were men. The cross-validation estimate of mean utility score was 0.76 (SD: 0.20), which was the same as the actual mean utility score. Of the 15 QLQ-C30 dimensions, 4 functional dimensions (physical, role, emotional, and social) and the pain symptom dimension were predictive of patient utility scores. Conclusions: Our study demonstrates the feasibility of deriving utility scores from prospective QoL data. Validation of the QLQ-C30 predictors found in this study could further the ability to estimate cost utility of therapies for economic evaluations.

Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial

Importance Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. Objective To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. Design, Setting, and Participants In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. Intervention Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. Main Outcomes and Measures Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)–positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. Results Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1–positive and PD-L1–negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment. Conclusions and Relevance Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1–positive and PD-L1–negative tumors. Further study of pembrolizumab for this group of patients is warranted. Trial Registration clinicaltrials.gov Identifier: NCT02335411

Role of palliative radiotherapy in the management of mural cardiac metastases: who, when and how to treat? A case series of 10 patients

Cardiac metastases (CM), although a rare manifestation of metastatic cancer, are increasing in incidence with the improved prognosis and increased longevity of many patients with cancer. This condition may be life‐threatening, especially for bulky rapidly growing tumors. Such cancer presentations may be amenable to palliative radiotherapy to improve symptoms and to prevent further cardiac function decline. Here, we report on our experience with 10 patients with mural CM who received radiotherapy (RT) to the heart with palliative intent. The radiation treatment was given in different clinical situations using different dose and fractionation, and with a variety of outcomes. Palliative RT was a reasonably effective treatment, leading to good radiographic response in five patients who were evaluable for radiologic response. The mean duration of response in responding patients was 6.3 months (range: 3–11 months). This report describing clinical dilemmas around CM radiation therapy summarizes the previous experiences with radiation in treatment of CM and may assist in the considerations of palliative treatment for these patients.

Postoperative chemoradiotherapy vs . preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy

BACKGROUND Worldwide, almost one million new cases of stomach cancer were diagnosed in 2012, making it the fifth most common cancer, and the third leading cause of cancer deaths. The current tumor node metastasis (TNM) staging system represents a consensus between the East and the West, and will serve as a strong foundation upon which to build future evidence. In this review article, we first discuss the definition and optimal surgery for locally advanced gastric cancer, followed by the general principles when considering a pre vs. postoperative radiotherapy (RT) strategy. We then provide a synthesis of the existing randomized trial evidence in an attempt clarify the role of pre and postoperative RT in the management of locally advanced gastric cancer. METHODS A Medline search 1966-Jun 2014 was undertaken. Randomized trials including patients with locally advanced gastric cancer (using established definitions), comparing RT [with or without chemotherapy (CT)], with surgery alone or other treatment modalities were included. Systematic reviews and evidence based practice guidelines that include this body of primary studies were preferentially discussed. Medline, Cochrane Library, Clinicaltrial.gov, Guidelines Clearinghouse were searched. RESULTS Sixteen randomized trials, three systematic reviews and one practice guideline were included as the evidence base. In this group of studies, two reports compared postoperative chemoradiotherapy (CRT) with surgery alone. Driven predominantly by INT0116, they established the role of postoperative CRT to provide a survival benefit in a patient group that underwent surgery with predominantly D0-1 dissections. Preoperative RT (four studies) showed promise for survival benefit but the risks of bias in these trials were high. Postoperative CRT compared with CT alone (eight trials) showed no survival benefit with the addition of radiation although some evidence of activity can be observed with improved local regional control. CONCLUSIONS AND FUTURE DIRECTIONS Technical expertise to enable the delivery of high quality RT to complex target volumes as is required in gastric cancer, and surgical standards to ensure the delivery of high quality surgery, have matured in recent years. Six trials with large sample sizes are currently ongoing to better define the role of preoperative CRT (two studies) and postoperative CRT (four studies), when used in conjunction with high quality surgery and RT, and contemporary CT regimens. The moderate likelihood of locoregional recurrences and the favorable therapeutic ratio with using RT preoperatively in other settings, provide optimism that preoperative CRT would have a pivotal role to play in locally advanced gastric cancer. Active accrual into ongoing trials is strongly encouraged.

Impact of an Oncology Palliative Care Clinic on Access to Home Care Services

Home care (HC) is important for patients with cancer as performance status declines. Our study of 1224 patients at a Canadian cancer center examined the impact of an oncology palliative care clinic (OPCC) on HC referral. The HC referral frequency was calculated before and after the first OPCC consultation, in total and according to performance status (Palliative Performance Scale, PPS). Characteristics associated with HC referral were investigated. After the first OPCC consultation, there was an increase in HC referral from 39% (477 of 1224; 49% of those with PPS ≤60) to 69% (841 of 1224; 88% of those with PPS ≤60). Factors independently associated with HC referral were poor PPS (P < .001) and older age (P = .003). Thus OPCC involvement resulted in markedly increased HC referrals, particularly for older patients with poor performance status.

A case of prolonged disease-free survival in a patient with choroidal metastasis from breast cancer

Background A 57-year-old woman presented with distorted vision and decreased visual acuity (finger count only) in her left eye, 6 years after she had undergone a lumpectomy, lymph-node dissection, and radiation therapy for a 1.1 cm infiltrating ductal carcinoma of her right breast. A year before this presentation, she had completed 5 years of adjuvant tamoxifen therapy.Investigations Physical examination, including a thorough ophthalmologic evaluation; laboratory investigations, ocular fluorescein angiography, ocular ultrasonography, head CT, chest X-ray, abdominal ultrasonography, bone scan, and bilateral mammography.Diagnosis Choroidal metastasis from breast carcinoma, with no other evidence of disease recurrence.Management Radiation therapy to the left eye followed by ongoing hormonal therapy with oral letrozole 2.5 mg daily for the past 9.5 years.

Long term responders to palliative chemotherapy for advanced biliary tract cancer.

BACKGROUND Patients with advanced biliary tract cancer (BTC) are often treated with palliative chemotherapy (PC). Standard PC since 2010 is a cisplatin/gemcitabine doublet, with median overall survival (OS) of 11.7 months from the ABC-02 trial. Prior to this, our institutional standard was gemcitabine and fluoropyrimidine. The ABC-02 study used 8 cycles of PC as standard with treatment stopped even in the absence of disease progression, but some patients may benefit from continuing PC longer than 8 cycles. METHODS Patients treated with at least 2 cycles of PC for advanced BTC in Princess Margaret Cancer Centre between 1987 and 2015 were included, and divided into 2 groups for analysis-long-term responders (LTR) who received 9 or more cycles, and controls (2-8 cycles). Data was collected on demographics, clinicopathological features, PC regimen, toxicities, and survival. The primary outcome measure was OS, with secondary analyses including progression-free survival (PFS) and toxicity rates between groups. RESULTS A total of 382 patients were identified, 123 who met the criteria for LTR and 259 who were included as controls. The baseline demographic and clinical characteristics were similar, although more patients in the control group had gallbladder cancer or extrahepatic cholangiocarcinoma than LTR (P=0.024), and more patients in the LTR group were treated with combination chemotherapy regimens (93% vs. 82% in controls, P=0.003). The LTR patients had significantly longer PFS (median 13.3 vs. 4.1 months, P<0.001) and longer OS than controls (median 22.1 vs. 9.2 months, P<0.001). In LTR patients, 15% had a break from chemotherapy of 3 months or more and restarted the same regimen. The LTR patients reported higher rates of nausea, cutaneous and hematologic toxicity, but also more frequently went on to receive second-line chemotherapy (47% vs. 33%, P=0.007). In multivariable analysis of OS, LTR, good performance status and intrahepatic site of cancer were associated with better survival. CONCLUSIONS From this institutional dataset, a significant proportion of patients continued chemotherapy past 8 cycles, and appeared to derive benefit from longer duration of treatment. Toxicity rates were higher in this group, but manageable as evidenced by second-line treatment rates. Discontinuation of chemotherapy for reasons other than toxicity or progression may result in loss of disease control and impact survival in this population; these data suggest the use of continued chemotherapy to disease progression in patients with advanced BTC is a favorable option.