Tinghua Zhang

Palliative systemic therapy for advanced non-small cell lung cancer: Investigating disparities between patients who are treated versus those who are not

BACKGROUND Palliative systemic therapy (ST) in advanced non-small cell lung cancer (NSCLC) is associated with improved overall survival (OS) and quality of life, yet many patients remain untreated. We explored differences between patients who did and did not receive palliative ST in order to gain evidence to support and advocate for the untreated. METHODS We performed a retrospective analysis of newly diagnosed patients with advanced, incurable NSCLC seen as outpatients at our institution between 2009 and 2012. Demographics, treatment, and survival data were collected. RESULTS 528 patients were seen: 291 (55%) received palliative ST, while 237 (45%) received none. Demographics were as follows: Median age 67, 55% male, 50% ECOG performance status (PS) 0-1, 48% with weight loss. Untreated patients were older (median 71 vs. 64, p<0.01), less fit (PS 0-1 in 27% vs. 69%, p<0.01), and more likely to have lost weight (57% vs. 41%, p<0.01). Reasons for no treatment included poor PS (67%) and patient choice (23%). Median OS was shorter amongst untreated patients (3.9 vs. 10.7 months, HR 1.80 [95% CI 1.4-2.3], p<0.01). In multivariate analysis, not receiving ST was associated with shorter OS. CONCLUSION Unsurprisingly, untreated patients had poorer prognostic features and worse OS. However, it is concerning that, despite being seen in an active academic center, nearly half of all referred patients with advanced NSCLC received no anti-cancer treatment. Current research primarily seeks to improve outcomes in treated patients with good PS. This review suggests that this is an inappropriate allocation of research effort. Our research should be more equitably split between good and poor performance patient groups if we are to improve the survival of all patients with advanced NSCLC. Potential strategies include more rapid diagnosis prior to functional decline, and the development of therapies effective and tolerated in a sicker population.

Palliative chemotherapy in advanced colorectal cancer patients 80 years of age and older

BACKGROUND Colorectal cancer (crc) has a median diagnostic age of 68 years. Despite significant progress in chemotherapy (ctx) options, few data on outcomes or toxicity from ctx in patients 80 years of age and older are available. We investigated ctx in such patients with metastatic crc (mcrc), hypothesizing high rates of hospitalization and toxicity. METHODS A retrospective chart review identified patients 80 years of age and older with mcrc who initiated ctx between 2005-2010 at our institution. Patient demographics and ctx data were collected. Endpoints included rates of hospitalization, ctx discontinuation because of toxicity, and overall survival. RESULTS In 60 patients, ctx was initiated on 88 occasions. Median age in the cohort was 83 years; 52% were men; 72% lived with family; 53% had a modified Charlson comorbidity index of 2 or greater; and 31% were taking 6 or more prescription medications at baseline. At baseline, 33% of the patients were anemic (hemoglobin < 100 g/L), 36% had leukocytosis (white blood cells > 11×10(9)/L), and 48% had renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m(2)). In 53%, ctx was given as first-line treatment. The initial ctx dose was adjusted in 67%, and capecitabine was the most common chemotherapeutic agent (45%). In 19 instances (22%), the patient was hospitalized during or within 30 days of ctx; in 26 instances (30%), the ctx was discontinued because of toxicity, and in 48 instances (55%), the patient required at least 1 dose reduction, omission, or delay. Median overall survival was 17.8 months (95% confidence interval: 14.3 to 20.8 months). CONCLUSIONS In the population 80 years of age and older, ctx for mcrc is feasible; however, most recipients will require dose adjustments, and a significant proportion will be hospitalized or stop ctx because of toxicity. Prospective research incorporating geriatric assessment tools is required to better select these older patients for ctx.

Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy

Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P = 0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

Approach to the non-operative management of patients with stage II non-small cell lung cancer (NSCLC): A survey of Canadian medical and radiation oncologists

BACKGROUND AND OBJECTIVES Standard management of stage II non-small cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. The optimal non-surgical management of stage II NSCLC is undefined. We surveyed Canadian oncologists to understand current practices. MATERIALS AND METHODS Canadian oncologists specializing in the management of lung cancer were invited by email to complete an anonymous, online survey developed by the research team. Physician demographics were recorded. Physicians were asked to comment on their practice and make treatment choices in eight clinical scenarios of inoperable stage II NSCLC. RESULTS Responses were received from 81/194 physicians (42% response rate), 57% medical and 42% radiation oncologists. Most physicians (90%) had a practice with at least 25% lung cancer patients and 85% were based at an academic institution. Across eight clinical patient scenarios, radical therapy was selected 79-98% of the time. Radical radiotherapy alone and concurrent chemoradiotherapy were the preferred options for these patients, while sequential chemoradiation was less favoured. Nodal status (N0 vs N1) did not influence choice of therapy (p 0.31), but the reason for patient inoperability did (p<0.0001). There was no significant difference in choice of therapy when comparing responses between medical vs radiation oncologists, academic vs community physicians, and physicians with high vs low proportion of lung cancer patients. CONCLUSION Most lung cancer physicians manage inoperable stage II NSCLC patients with curative intent, but consensus on how to optimally employ radiotherapy and/or chemotherapy is lacking. Future prospective, randomized trials are warranted.

Radical Treatment of Stage II Non–small-cell Lung Cancer With Nonsurgical Approaches: A Multi-institution Report of Outcomes

Introduction Standard management of stage II non–small‐cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. We examined outcomes in this defined patient group. Methods We reviewed the records of patients with stage II NSCLC treated nonsurgically with curative intent from 2002 to 2012 across 3 academic cancer centers. Data collected included demographics, comorbidities, staging, treatments, and survival. The primary endpoint was overall survival (OS). We assessed factors associated with treatment choice and OS. Results A total of 158 patients were included: the median age was 74 years (range, 50‐91 years), 44% were female, and 68% had a performance status of 0 to 1. The stage II groupings of the patients were T2b‐T3 N0 in 55% and N1 in 45%. The most common reasons for inoperability were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median, 60 Gy [range, 48‐75 Gy]). Seventy‐three percent received RT alone; 24% received concurrent and 3% sequential chemoradiotherapy (CRT). In multivariate analyses, CRT was less likely in older patients (≥ 70 years) (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11‐0.70; P = .006) and in patients with higher (> 5) Charlson comorbidity scores (OR, 0.34; 95% CI, 0.13‐0.90; P = .03) or normal (< 10 × 109/L) white blood cell counts (OR, 0.26; 95% CI, 0.09‐0.73; P = .01). At the time of our analysis, 74% have died. The median OS was 22.9 months (range, 17.1‐26.6 months). Patients who had undergone CRT had a significantly longer median OS than those receiving RT alone (39.1 vs. 20.5 months; P = .0019), confirmed in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21‐0.69; P = .001). Conclusion Nonsurgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared with RT alone. A randomized trial may be warranted. Micro‐Abstract The optimal nonoperative management of stage II non–small‐cell lung cancer is undefined, with limited data to guide decision‐making in this setting. We reviewed treatment patterns and outcomes of 158 patients in this defined group. The majority (73%) received radical radiotherapy alone; however, those treated with combined‐modality chemoradiation had significantly longer median survival (39.1 vs. 20.5 months; P = .0019). A randomized trial is warranted.

The Impact of Baseline Edmonton Symptom Assessment Scale Scores on Treatment and Survival in Patients With Advanced Non–small-cell Lung Cancer

Background Palliative systemic therapy is frequently underutilized in patients with advanced non–small‐cell lung cancer (NSCLC), for many reasons. The aim of this study was to identify patient‐reported factors that may predict for treatment decisions and survival in advanced NSCLC, using the Edmonton Symptom Assessment Scale (ESAS), which is a self‐reported questionnaire that quantifies symptom burden by asking patients to rate the severity of 9 common symptoms. Patients and Methods With ethics approval, we analyzed ESAS scores at initial oncology consultation for 461 patients with advanced NSCLC seen at The Ottawa Hospital Cancer Centre from 2009 to 2012. Subgroup analysis was performed to determine if treatment strategies or overall survival (OS) were related to the total symptom burden, as defined by the sum of the individual ESAS symptom scores. Results The severity of the ESAS total symptom burden score was positively correlated with Eastern Cooperative Oncology Group performance status (R = 0.48; P < .0001). Furthermore, patients with a higher symptom burden were less likely to receive systemic chemotherapy than those with fewer symptoms (43% vs. 66%; P < .0001), and had a significantly reduced OS (5.5 vs. 9.9 months; P < .0001). A higher ESAS symptom burden score was also associated with reduced OS by univariate analysis (hazard ratio, 1.78; 95% confidence interval, 1.45‐2.18; P < .0001), although multivariate analysis showed only a trend towards significance (hazard ratio, 1.27; 95% confidence interval, 0.99‐1.62; P = .06). Conclusions Overall, this demonstrates a novel role for the ESAS as a prognostic tool that could complement existing patient assessment models, such as Eastern Cooperative Oncology Group performance status, in the development of optimal treatment plans and estimation of survival, in patients with advanced lung cancer. Micro‐Abstract The rate of receipt of systemic therapy in advanced lung cancer is low. Here, we used the Edmonton Symptom Assessment Scale to identify patient‐reported factors that may contribute to this. Results found that patients with a higher symptom burden were less likely to receive chemotherapy and had a reduced overall survival. Targeted intervention of these symptoms could help improve both quality of life and performance status.