Utility of a new prognostic score based on the Comprehensive Complication Index (CCI®) in patients operated on for colorectal cancer (S-CRC-PC score)

BackgroundPostoperative complications after colorectal cancer surgery have been associated with poor long-term prognosis. The aim of the present study was to investigate the prognostic impact of postoperative complications after colorectal cancer surgery assessed by the Comprehensive Complication Index (CCI®) and designing a new prognostic score based on this index.MethodsThis observational longitudinal study included a series of 604 patients who underwent colorectal surgery for cancer. Demographic data, comorbidity measured by Charlson Index, tumor characteristics, surgical data and postoperative complications were recorded as predictors. Univariate and multivariate analysis were performed and long-term survival was the output variable. Based on Hazard Ratios obtained on multivariate analysis, a new score, S-CRC-PC, was created for predicting long-term survival.ResultsTwo-hundred and twelve (35.1%) patients developed some postoperative complication. The mean CCI was 11.6 (±19.19). Mild complications (CCI <26.2) were detected in 95 (15.7%) patients. Moderate complications (CCI 26.2–42.2) were detected in 64 (10.6%) patients. Severe complications (CCI >42.3) were detected in 53 patients (8.8%) patients. Mortality rate was 1.7%. In multivariate analysis, age (p < 0.001), Charlson score (p = 0.014), CCI (p < 0.001), and TNM stage (p < 0.001) were statistically significantly in relation to long-term survival rate. S-CRC-PC score was statistically associated with survival rate (HR: 1.34–95% CI: 1.27–1.41). Patients with S-CRC-PC values from 0 to 8 points (low risk), 8.1–16 points (medium risk), and scores above 16 points (high risk) had a cumulative survival rate at five-years of 98%, 83%, and 31% respectively.ConclusionsPostoperative complications after colorectal cancer surgery assessed by CCI are an independent prognostic factor of survival rate. The S-CRC-PC score may be helpful in predicting long-term cancer outcomes.     

Impact of comorbidity on mortality: a cohort study of 62,591 Danish women diagnosed with early breast cancer, 1990-2008

The incidence of breast cancer, as well as other chronic disease, increases with age, older breast cancer patients being more likely than younger to suffer from other diseases at time of diagnosis. Our objective was to assess the effect of comorbidity on mortality after early breast cancer. 62,591 women diagnosed with early breast cancer 1990–2008 were identified using the Danish Breast Cancer Cooperative Group Registry. Data were linked to the Danish National Patient Register and the Danish Register of Causes of Death. Main outcome measures were mortality from all causes, breast cancer, and non-breast cancer causes in relation to Charlson comorbidity index (CCI). Compared with patients without comorbidity (CCI 0), the presence of comorbidity increased the risk of dying from breast cancer as well as other causes with adjusted hazard ratios (HRs) for all-cause mortality of 1.45 (CI 95% 1.40–1.51) for CCI 1, 1.52 (95% CI 1.45–1.60) for CCI 2, and 2.21 (95% CI 2.08–2.35) for CCI 3+. Equivalent HRs for breast cancer-specific mortality were 1.30 (95% CI, 1.24–1.36) for CCI 1, 1.31 (95% CI 1.23–1.39) for CCI 2, and 1.79 (95% CI, 1.66–1.93) for CCI 3+ (all P values < 0.0001). For patients with CCI 0, 5-year overall survival increased over time from 72.5% (95% CI, 71.7–73.3%) in 1990–1994 to 81.6% (95% CI, 80.9–82.2) in 2000–2004, whereas the 5-year overall survival remained stable around 43% among the patients with CCI 3+. This population-based cohort study shows that compared with patients without comorbidity, the risk of dying from breast cancer as well as other causes increased significantly with increasing CCI score. While survival improved over time for patients without comorbidity, no improvement was seen among patients with severe comorbidity (CCI 3+).     

Improved Survival of Stage I Non–Small Cell Lung Cancer: A VA Central Cancer Registry Analysis

IntroductionThe combined impact of advances in diagnosis and treatment of stage I NSCLC has not been assessed comprehensively. To define the survival impact of modern staging and treatment techniques for clinical stage I NSCLC, the Veterans Administration Central Cancer Registry, a database of U.S. veterans in whom the disease was diagnosed in the Veteran’s Health Administration, was queried. From this database, patients who had stage I NSCLC diagnosed from 2001 to 2010 and were treated with either surgery or radiation were identified.MethodsOverall survival (OS) and lung cancer–specific survival were determined. Propensity score matching and Cox multivariate analysis were used to adjust for baseline patient characteristics.ResultsA total of 11,997 patients were identified. The 4-year OS rate increased from 38.9% to 53.2% from 2001 to 2010 for all patients. Positron emission tomography and endobronchial ultrasound did not improve OS. Survival of radiated patients improved from 12.7% to 28.5%. The introduction of stereotactic body radiation therapy (SBRT) significantly improved OS (hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.54–0.68) and lung cancer–specific survival (HR = 0.39, 95% CI: 0.32–0.46) compared with conventionally fractionated radiation. The 4-year OS rate also improved after surgery (from 51.5% to 66.5%). This increase was associated with use of adjuvant chemotherapy, increased use of video-assisted thoracoscopic surgical procedures, and decreased pneumonectomy rates, with similar survival between open and video-assisted thoracoscopic surgical procedures. OS after lobectomy was superior to that after sublobar resection (HR = 0.82, 95% CI: 0.75–0.89). In the era of available SBRT (2008–2010), 4-year OS was not significantly different after sublobar resection or lobectomy for medically unfit patients (Charlson comorbidity index = 2) (55.4% and 58.1%, respectively; p = 0.69) but was significantly worse for fit patients (Charlson comorbidity index = 0–1) undergoing sublobar resection (55.5% and 68.0%, respectively; p < 0.001).OS (HR = 0.36, 95% CI: 0.35–0.38) and lung cancer–specific survival (HR = 0.31, 95% CI: 0.29–0.33) were improved after surgery as compared with after radiation, with the improvement maintained on matched comparison of lobectomy and SBRT.ConclusionsOS increased in veterans with a diagnosis of stage I NSCLC from 2001 to 2010; the increase was coincident with improved radiation and surgical techniques.     

Cognitive decline after major oncological surgery in the elderly

BackgroundElderly patients undergoing oncological surgery experience postoperative cognitive decline. The aims of this study were to examine the incidence of cognitive decline 3 months after surgery and identify potential patient-, disease- and surgery-related risk factors for postoperative cognitive decline in onco-geriatric patients.MethodsA consecutive series of elderly patients (≥65 years) undergoing surgery for the removal of a solid tumour were included (n = 307). Cognitive performance was assessed pre-operatively and 3 months postoperatively. Postoperative decline was defined as a decline in scores of cognitive tests of ≥25% on ≥2 of 5 tests.ResultsOf the patients who had completed the assessments, 117 (53%, 95% confidence interval [CI]: 47–60) had improved cognitive test scores, whereas 26 (12%, 95% CI: 7.6–16) showed cognitive decline at 3 months postoperatively. In patients aged >75 years, the incidence of overall cognitive decline 3 months postoperatively was 18% (95% CI: 9.3–27). In patients with lower pre-operative Mini–Mental State Examination (MMSE) score (≤26) the incidence was 37% (95% CI: 18–57), and in patients undergoing major surgery it was 18% (95% CI: 10.6–26). Of the cognitive domains, executive function was the most vulnerable to decline.ConclusionAbout half of the elderly patients show improvement in postoperative cognitive performance after oncological surgery, whereas 12% show cognitive decline. Advanced age, lower pre-operative MMSE score and major surgery are risk factors for cognitive decline at 3 months postoperatively and should be taken into account in the clinical decision-making progress. Research to develop interventions to preserve quality of life should focus on this high-risk subpopulation.     

Frailty and health related quality of life three months after non-metastatic colorectal cancer diagnosis in older patients: A multi-centre prospective observational study

BackgroundHealth related quality of life (HRQL) is an important outcome measure in geriatric oncology. Surgery is the main treatment for colorectal cancer (CRC) but has been associated with a loss of HRQL in older patients. This study aimed to identify determinants for a decreased HRQL at three months after CRC diagnosis.MethodThis multi-centre observational cohort study (NCT04443816) included 273 patients aged ≥70 years diagnosed with non-metastatic CRC. A multi-domain frailty screening was performed in each patient. A decreased HRQL was defined as a mean difference ≥ 10 on the EORTC QLQ-C30 questionnaire between baseline and three months after CRC diagnosis. Determinants of a decreased HRQL were analysed using multivariable logistic regression.ResultsA decrease in HRQL occurred in 63 patients (23.1%). Non-surgical patients had the highest risk of decreased HRQL three months after diagnosis (adjusted odds ratio (OR) 6.4 (95% confidence interval (CI) 2.0–19.8)). The Charlson Comorbidity Index (CCI) (aOR 2.3 (95% (CI) 1.2–4.2)), the American Association of Anesthesiologists class (aOR 2.6 (95%CI 1.4–4.9)), impaired daily functioning (aOR 2.7 (95%CI 1.3–5.6)) and dependent living (aOR 1.9 (95%CI 1.1–4.5)) were associated with a decreased HRQL, mainly caused by non-surgical patients. In surgical patients, a major postoperative complication was a strong determinant of decreased HRQL and was associated with preoperative comorbidity and cognitive impairment (aOR 4.0 (95%CI 1.9–8.8)).ConclusionFrailty characteristics are highly prevalent in older patients at time of CRC diagnosis but not strongly associated with a decreased HRQL after three months. Non-surgical patients and patients with major postoperative complications had the highest risk of decreased HRQL.Registered at clinicaltrials.gov trial number: NCT04443816     

Duration of short-acting granulocyte colony-stimulating factor for primary prophylaxis and risk of neutropenia-related hospitalization in older patients with cancer

PurposeEvaluate the relationship between duration of primary prophylactic short-acting granulocyte colony-stimulating factor (PP-sG-CSF) and risk of neutropenia-related hospitalization (NRH) in older patients receiving myelosuppressive chemotherapy.MethodsUsing the Medicare claims database, we conducted a nested case-control study in a cohort of patients aged ≥66 years with breast, colorectal, lung, ovarian, or prostate cancer, or non-Hodgkin lymphoma who initiated a first cycle of any myelosuppressive chemotherapy January 1, 2008–September 30, 2016, and received PP-sG-CSF. We matched up to four controls to each NRH case by age, cancer type, regimen febrile neutropenia (FN) risk category, and year using incidence density sampling. We used conditional logistic regression adjusted for race, sex, and modified Charlson comorbidity index (CCI) to estimate relative risk of NRH related to duration of PP-sG-CSF categorized as <5 and ≥ 5 days.ResultsOf 2148 patients receiving PP-sG-CSF, 108 (5%) experienced NRH in the first cycle. We matched 333 controls to 96 cases. Cases were similar to controls in mean age, tumor type, and intermediate/high-risk regimen, but were more likely to have CCI ≥5 and less likely to use PP-sG-CSF ≥5 days (31% vs. 39%). Adjusted ORs (95% CI) for NRH were 0.69 (0.40–1.19) for ≥5 vs. <5 days of PP-sG-CSF among patients receiving any myelosuppressive chemotherapy, 0.43 (0.21–0.89) for intermediate/high-risk regimen, and 0.42 (0.19–0.89) for any myelosuppressive chemotherapy with all agents given on cycle day one only.ConclusionsAmong older patients with cancer who are receiving PP-sG-CSF, ≥5 days of use was associated with substantial reduction in NRH risk.     

Risk of suicide in men with low-risk prostate cancer

PurposeRisk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing.Patients and MethodsRelative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997–2009 to 528,658 matched prostate cancer-free men.ResultsDuring the first 6 months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000 PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0–10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000 PY, RR 10 (95% CI 5.1–21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000 PY and RR 5.2 (95% CI 2.3–12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000 PY, RR 1.0 (95% CI 0.68–1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000 PY, RR 1.8 (95% CI 1.1–2.9).ConclusionAlthough the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness.     

Significance of pretreatment comorbidities in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitor

A standard, valid assay of comorbidities for elderly patients with advanced non-small-cell lung cancer (NSCLC) who have received antitumor therapy is needed to provide useful prognostic information. The aim of this study was to analyze prognostic factors and validate classic Charlson comorbidity index (CCI) and comorbidity scores in elderly patients with advanced NSCLC treated with chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). A retrospective analysis was conducted on 162 patients with advanced NSCLC over 70 years old at diagnosis, who were treated with cytotoxic chemotherapy or with EGFR-TKIs between April 2003 and April 2009 at Kyoto University Hospital. Collected data included clinical assessments, treatments, toxicities, and outcomes. Survival was estimated using the Kaplan–Meier method. Prognostic factors were evaluated with log-rank and Cox regression tests. Based on multivariate analysis, unspecified NSCLC histology [Hazard ratio (HR), 1.631; 95% Confidence interval (CI), 1.184–2.263; P = 0.0016], more than 3 comorbidities (HR, 1.317; 95% CI, 1.020–2.675; P = 0.0350), and a CCI of more than 3 (HR, 1.321; 95% CI, 1.031–1.664; P = 0.0285) were significant independent negative prognostic factors for survival. Our results indicate that CCI and the number of comorbidities are independent predictors of survival in elderly patients undergoing systemic chemotherapy including EGFR-TKIs for advanced NSCLC. These factors should be taken into consideration in the pretreatment assessment as important factors predicting survival outcome.     

Electronic FRAIL score may predict treatment outcomes in older adults with myeloma

IntroductionFrailty is a known risk factor for older patients with myeloma. Here we present realworld data using a computer-generated frailty assessment score (FRAIL score), based on 5 clinically derived parameters, in predicting patient outcomes.MethodsOlder patients with newly diagnosed multiple myeloma who received frontline treatment with cyclophosphamide-bortezomib-dexamethasone had their FRAIL score retrospectively assessed. Treatment outcomes were assessed using standard IMWG criteria, and event free survival and overall survival determined.Results155 patients were analysed. Compared to those who were assessed as non-frail (FRAIL score 0–1) likely-frail patients (score ≥ 2) were less likely to complete the full course of treatment (24.3% vs 53.4%, p = 0.002), and more likely to terminate treatment due to toxicities (35.1% vs 22.0%, p = 0.109), as well as having a greater number of patients stop treatment early for reasons other than toxicity or progression (27.0% vs 10.2%, p = 0.010). After a median follow up of 42.5 months, likely-frail patients were found to have a trend for shorter event-free survival (median EFS, 8.7 vs 17.9 months, p = 0.064) and statistically inferior overall survival (median OS, 30.2 vs 49.8 months, p < 0.001). After adjusting for age, stage, and Charlson comorbidity index, FRAIL score was prognostic for OS (HR = 3.47, 95% CI 1.88–6.4), but not EFS (HR = 1.28, 95%CI 0.79–2.06).ConclusionThe FRAIL score is independently predictive of overall survival in older patients with myeloma receiving bortezomib-based induction chemotherapy and can help identify those patients more likely to experience treatment toxicity.     

Results and impact of routine assessment of comorbidity in elderly patients with non-small-cell lung cancer aged > 80 years

BACKGROUND: Elderly patients now represent a bigger proportion of patients with non-small-cell lung cancer (NSCLC). However, data from clinical trials are limited for this age group, and the elderly are often excluded from optimal treatment for several reasons, including comorbidity. PATIENTS AND METHODS: We reviewed a 10-year experience on proven patients with NSCLC aged > 80 years; comorbidity was assessed using the Charlson Comorbidity index (CCI). The main objective was the impact of comorbidity on survival outcome. RESULTS: Of 109 managed patients aged > 80 years, 74 patients had a proven diagnosis of NSCLC. Performance status was < 2 in 58 patients and TNM classification of malignant tumors was I-II, IIIA-IIIB, and IV in 18, 27, and 29 patients, respectively. Comorbidity was present for 49 patients. Charlson Comorbidity Index ranged from 4 to 12 with 31 patients having a CCI >or= 6. Sixteen patients received supportive care only, whereas 23 patients were operated on, 12 received radiation therapy, and 23 had chemotherapy. Eight grade 3/4 toxicities were reported (3 patients discontinued treatment). Multivariate analysis demonstrated a significant increase in the risk of death for patients with a poor Eastern Cooperative Oncology Group performance status (hazard ratio, 2.64; 95% confidence interval, 1.3-5.36; P = 0.007) and an advanced TNM stage (hazard ratio, 3.31; 95% confidence interval, 1.99-5.5; P < 0.00001). Although statistic significance was not reached, a difference in overall survival was shown between patients with a CCI < 6 and CCI >or= 6 (12.2 months vs. 8.2 months; P = 0.08). CONCLUSION: These results support a role for the CCI as a routine means to assess comorbidity, because patients with fewer comorbidities tolerate and derive survival benefit of optimal NSCLC management. These findings must be confirmed in prospective studies.     

Impact of Treating Physician on Radiation Therapy Related Severe Toxicities in Men with Prostate Cancer

PurposeThe impact of treating physician on radiation therapy (RT) related toxicity is unclear. We carried out a secondary analysis of a randomized controlled study to determine whether the risk of RT–related late toxicities in patients with prostate cancer varies depending on the treating radiation oncologist.Methods and MaterialsThis is a secondary analysis of a phase 3 randomized controlled study in which patients with prostate cancer with Gleason score ≤7, clinical stage T1b-T3a, and prostate-specific antigen <30 ng/mL were randomized to receive androgen suppression for 6 months, starting either 4 months before or concurrently with definitive prostate radiation therapy. Incidence of late RT–related toxicity was estimated using Kaplan–Meier methods. We applied multivariable semiparametric shared frailty models with gamma distribution to determine the between-physician variation in the hazard of late RT–related grade ≥3 gastrointestinal, genitourinary, or overall toxicity. Patient level covariables included age, risk group, year of enrollment, and treatment regimen. Frailty variance, a measure of unexplained heterogeneity, was estimated with 95% confidence intervals (CIs). Statistical significance was suggested when the lower limit of the 95% CI for the frailty variance was >0. The Commenges–Andersen test was used for P value estimation.ResultsOverall, 426 patients were treated by 9 radiation oncologists. On log-rank test, there was a significant difference in the cumulative incidence of overall grade ≥3 toxicities (P = .001) and grade ≥3 gastrointestinal toxicity (P = .01) among the physician-based clusters. The frailty variance for overall late grade ≥3 toxicity was 0.31 (95% CI, 0.02-1.39; P = .01). The frailty variance for the grade ≥3 gastrointestinal and genitourinary toxicity was 0.84 (95% CI, 0.00-4.20; P = .11) and 0.11 (95% CI, 0.00-1.13; P = .31), respectively.ConclusionsIn our study, the hazard of overall RT-related late grade ≥3 toxicity varied significantly depending on treating radiation oncologist. Further studies are required to explore the underlying processes that lead to such variations in clinical trials involving radiation therapy in prostate cancer.     

The value of C-reactive protein and comorbidity in predicting survival of patients with high grade soft tissue sarcoma

BackgroundThe aim of this study was to determine whether C-reactive protein (CRP) levels or patient’s comorbidity before treatment predicted the overall disease-specific survival and local tumour control in high grade soft tissue sarcoma patients.MethodsA total of 332 primary adult soft tissue sarcoma patients were retrospectively reviewed. CRP levels were obtained prior to treatment for all patients. The Charlson comorbidity index (CCI) was used for evaluation as a measure of comorbidity. Patients that presented with metastases at diagnosis were excluded from this study.ResultsElevated CRP levels were seen in 152 patients. CCI score varied from 0 to 4. Two-hundred and sixty-five patients had a score of 0 (no identified comorbidity), and 67 patients had a score of 1 or more. Patients with elevated CRP levels prior to initial treatment had a poorer disease-specific survival (42% at 5 years) than patients with normal CRP levels (82% at 5 years) (p < 0.0001). Patients with elevated CRP levels had a poorer local recurrence-free rate after initial treatment (75% at 5 years) than patients with normal CRP levels (89% at 5 years) (p = 0.0004). Multivariate analysis also showed the preoperative CRP level to be an independent predictor of survival and local control. Although age in patients with identified comorbidity was significantly higher than those in patients with no-identified comorbidity, CCI was not a predictive factor for either survival or local control.ConclusionPretreatment elevated CRP levels were found to be a poor prognostic factor for disease-specific survival and local control for soft tissue sarcoma patients.     

Sarcopenia is an effective prognostic indicator of postoperative outcomes in laparoscopic-assisted gastrectomy

BackgroundThe association between sarcopenia and postoperative outcomes in patients who undergo laparoscopic-assisted gastrectomy is unclear. We aimed to determine the predictive value of sarcopenia for adverse postoperative outcomes after laparoscopic-assisted gastrectomy for gastric cancer.Materials and methodsWe prospectively collected the clinical data of patients who underwent elective radical laparoscopic-assisted gastrectomy for gastric cancer in two large centers from August 2014 to October 2017. The third lumbar vertebra skeletal muscle index, handgrip strength, and 6-m usual gait speed were measured to diagnose sarcopenia. Subsequently, we aimed to identify the risk factors for postoperative complications.ResultsThe study included 313 patients and 37 (11.8%) patients were classified as sarcopenic. Compared with non-sarcopenic patients, sarcopenic patients were significantly older (P < 0.001), had higher nutritional risk screening 2002 scores (P = 0.013), Charlson comorbidity index (CCI) scores (P = 0.033), and neutrophil to lymphocyte ratio (P = 0.004), and lower body mass index (P < 0.001), preoperative serum albumin (P < 0.001), and hemoglobin (P < 0.001). Sarcopenic patients had higher postoperative complication rate (P = 0.002), longer postoperative hospital stays (P = 0.020) and higher total cost of hospitalization (P = 0.001). Multivariate analysis revealed that CCI score ≥1 (odds ratio [OR]: 2.424, 95% confidence interval [CI]: 1.309–4.487; P = 0.005) and sarcopenia (OR: 2.752, 95% CI: 1.274–5.944; P = 0.010) were independent risk factors for short-term postoperative complications.ConclusionSarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy.     

The effect of comorbidity on stage-specific survival in resected non-small cell lung cancer patients

AimTo quantify the effect of comorbidity on stage-specific survival in resected non-small cell lung cancer (NSCLC) patients.MethodsFrom the Danish Lung Cancer Registry, 20,461 patients diagnosed with lung cancer between 1st January 2005 and 31st December 2010 were identified. Among 3152 NSCLC patients who underwent surgical resection, mortality hazard ratios were calculated during three consecutive time periods following surgery (0–1 month, 1 month–1 year and >1 year) according to Charlson comorbidity score (CCS 0, 1, 2, 3+), Eastern Cooperative Oncology Group (ECOG) performance status, lung function, age, sex, pathological T (pT) and N (pN) stage using Cox proportional hazard modelling. The Kaplan Meier method was used to describe stage-specific survival according to the CCS.ResultsSevere comorbidity (CCS 3+) was independently associated with significantly higher death rates throughout the three periods of follow-up [Hazard ratio (HR) 2.06 (1.13–3.75) for CCS 3+ in 0–1 month, 1.57 (1.17–2.12) 3+ during1 month–1 year and 1.84 (1.42–2.37) after 1 year]. Stage-specific 5-year survival in patients with severe comorbidity was significantly lower than in patients without comorbid disease [e.g. 38% (95% confidence interval (CI) 23–53%) for pT1 and CCS 3+ versus 69% (62–75%) for pT1 and CCS 0].ConclusionSevere comorbidity affects survival of NSCLC patients who undergo surgical resection by as much as a single stage increment and this effect persists throughout follow-up. Further research may be necessary to help identify which patients are most likely to benefit from surgery.     

Influence of Medical Comorbidities on the Presentation and Outcomes of Stage I-III Non–Small-Cell Lung Cancer

BackgroundNon–small-cell lung cancer presentation, treatment, and outcomes vary widely according to socioeconomic factors and other patient characteristics. To determine whether medical comorbidities account for these observations, we incorporated a validated medical comorbidity index into an analysis of patients diagnosed with stage I to III NSCLC.Patients and MethodsWe performed a retrospective analysis of consecutive patients diagnosed with stage I to III NSCLC. Demographic, tumor, and comorbidity data were obtained from hospital tumor registries and individual patient records. The association between variables was assessed using multivariate logistic regression and survival analysis.ResultsA total of 454 patients met criteria for analysis. The median age was 65 years, and 51% were men. Individuals with a higher Charlson Comorbidity Index (CCI) were significantly more likely to present with early stage (stage I-II) NSCLC than were patients with lower CCI (odds ratio, 1.72; 95% confidence interval, 1.14-2.63; P = .01), although this association lost statistical significance (P = .21) in a multivariate model. In multivariate logistic regression, overall survival remained associated with all variables: age, sex, race, insurance type, stage, histology, and CCI (P = .0007). The CCI was associated with survival for patients with early stage (P = .02) and locally advanced (P = .02) disease.ConclusionIn this cohort of patients with stage I to III NSCLC, increasing comorbidity burden had a nonsignificant association with diagnosis at earlier disease stage. Although comorbidity burden was significantly associated with outcome for early stage and locally advanced disease, it did not account for survival differences based on multiple other patient and disease characteristics.     

The role of comorbidities on the uptake of systemic treatment and 3-year survival in older cancer patients

BackgroundOlder patients are notably absent from clinical trials. Thus, observational studies are the primary avenue for understanding the role of comorbidity in cancer care and survival. We examined the impact of comorbidity on systemic treatment initiation and 3-year survival in a cohort of older cancer patients.Patients and MethodsOur cohort comprised 2753 Australian veterans aged ≥65 years with full health coverage and a cancer registry notification for colorectal (CRC), breast, prostate or non-small-cell lung cancer (NSCLC). We established comorbidities based on drugs prescribed in the 6 months prior to cancer diagnosis.ResultsPatients with higher comorbidity burden were more likely to receive systemic treatment for prostate cancer [adjusted odds ratio 1.21, 95% confidence interval (CI) 1.05–1.39] but less likely for NSCLC (0.63, 95% CI 0.45–0.86). After adjusting for receipt of treatment, increased comorbidity resulted in shorter survival for CRC [adjusted hazard ratio (aHR) 1.16, 95% CI 1.07–1.26] and breast cancer (aHR 1.23, 95% CI 1.02–1.48). However, we did not demonstrate significant improvements in 3-year survival for patients receiving systemic treatment.ConclusionComorbidity influences systemic treatment uptake and adversely affects survival, with impact dependent upon comorbidity and cancer type. Clinical trials should be undertaken in older patients to better understand the risks and benefits of cancer treatments.     

Overtreatment of men with low-risk prostate cancer and significant comorbidity

BACKGROUND:

Men with low‐risk prostate cancer and significant comorbidity are susceptible to overtreatment. The authors sought to compare the impact of comorbidity and age on treatment choice in men with low‐risk disease.

METHODS:

The authors sampled 509 men with low‐risk prostate cancer diagnosed at the Greater Los Angeles and Long Beach Veterans Affairs Medical Centers between 1997 and 2004. Rates of aggressive treatment (radical prostatectomy, radiation therapy, brachytherapy) were determined among men of different ages and with different Charlson comorbidity scores. Multivariate modeling was used to determine the influence of both variables in predicting nonaggressive treatment, and Cox proportional hazards analysis was used to compare the risk of other‐cause mortality among groups according to Charlson score and age.

RESULTS:

Men with Charlson scores ≥3 were treated aggressively in 54% of cases (30 of 56 men), while men aged >75 years at diagnosis were treated aggressively in 16% of cases (7 of 44 men). In multivariate analysis, age >75 years was a much stronger predictor of nonaggressive treatment (relative risk, 12.0; 95% confidence interval [CI], 5.4‐28.3) than a Charlson score ≥3 (relative risk, 2.0; 95% CI, 1.3‐2.9). In survival analysis, men with Charlson scores ≥3 had an 8‐fold increased risk (hazard ratio, 8.4; 95% CI, 4.2‐16.6) and 70% probability of other‐cause mortality at 10 years, whereas age >75 years was associated with a 5‐fold increased risk (hazard ratio, 4.9; 95%CI, 1.7‐13.8) and a 24% probability of other‐cause mortality.

CONCLUSIONS:

Men with significant comorbidity often were overtreated for low‐risk prostate cancer. Like advanced age, significant comorbidity should be a strong relative contraindication to aggressive treatment in men with low‐risk disease. Cancer 2011. © 2010 American Cancer Society.     

Identifying frailty in clinically fit patients diagnosed with hematological malignancies using a simple clinico-biological screening tool: The HEMA-4 study

IntroductionThis study aims to develop and validate a simple score to estimate survival in the older population suffering from malignant hemopathies.MethodsWe prospectively recruited 285 patients, aged ≥65 years, admitted to receive chemotherapy. At inclusion, a geriatric assessment was performed. Cox proportional hazards models were performed to assess correlations between vulnerabilities and one-year survival. We developed a frailty score, HEMA-4, based on the most powerful prognostic factors. It was externally confirmed with an independent cohort.ResultsIn the development cohort, 206 patients were evaluable. Mean age was 76 years (range 65–90). The HEMA-4 score was created based on four independent predictive factors for survival: cognitive impairment (MMSE<27), comorbidities (≥2 on Charlson comorbidity index), CRP (≥10 mg/L) and low albumin level (<35 g/L). The population was stratified into three groups: good prognosis (score = 0–1, n = 141), intermediate prognosis (score = 2, n = 37) and poor prognosis (score = 3–4, n = 28). Their respective one-year survival was 74%, 51% (HR = 2.30; 95% CI =1.31–4.05; p < 0.01) and 36% (HR = 3.95; 95% CI =2.23–6.98; p < 0.01). In the validation cohort (n = 25), the one-year survival was 78% in the good prognosis group (n = 9) and 50% in the intermediate prognosis group (n = 6). The poor prognosis group had a median survival of four months in the development cohort and six months in the validation cohort (n = 10).ConclusionThe HEMA-4 score is a simple score that combines cognitive impairment, comorbidities, inflammation and low albumin level. Our data suggest that it predicts survival among older patients suffering from malignant hemopathies referred to receive chemotherapy regardless of their chronological age.     

Impact of comorbidity on survival in peripheral T‐cell lymphomas: A Swedish Lymphoma Registry study

Comorbidity impacts survival in B‐cell lymphoma patients, but the influence in peripheral T‐cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P < .001) and progression‐free survival (HR 1.54, P < .001) in multivariate analysis. In patients undergoing front‐line autologous stem cell transplantation (auto SCT), CCI >0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low‐intensity treatments. Among patients aged ≥75 years (n = 214), low‐intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front‐line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline‐based chemotherapy in elderly PTCL patients might be of limited benefit.     

Does comorbidity interact with colorectal cancer to increase mortality? A nationwide population-based cohort study

Background:

It is unknown whether comorbidity interacts with colorectal cancer (CRC) to increase the rate of mortality beyond that explained by the independent effects of CRC and comorbid conditions.

Methods:

We conducted a cohort study (1995–2010) of all Danish CRC patients (n=56 963), and five times as many persons from the general population (n=271 670) matched by age, gender, and specific comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index (CCI) scores. We estimated standardised mortality rates per 1000 person-years, and calculated interaction contrasts as a measure of the excess mortality rate not explained by the independent effects of CRC or comorbidities.

Results:

Among CRC patients with a CCI score=1, the 0–1 year mortality rate was 415 out of 1000 person-years (95% confidence interval (CI): 401, 430) and the interaction accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person-years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the interaction accounted for 34% of the mortality (interaction contrast=262 out of 1000 person-years, 95% CI: 215, 310). The interaction between CRC and comorbidities had limited influence on mortality beyond 1 year after diagnosis.

Conclusion:

Successful treatment of the comorbidity is pivotal and may reduce the mortality attributable to comorbidity itself, and also the mortality attributable to the interaction.