Erika Ramsdale

A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era

We investigated a recent (January 1999 to December 2009) cohort of 95 elderly Hodgkin lymphoma subjects. At diagnosis, median age was 67 years (range, 60-89 years), whereas 61% had significant comorbidity, 26% were unfit, 17% had a geriatric syndrome, and 13% had loss of activities of daily living. Overall response rate to therapy was 85%, whereas incidence of bleomycin lung toxicity was 32% (with associated mortality rate, 25%). With 66-month median follow-up, 2-year and 5-year overall survival were 73% and 58%, respectively (advanced-stage, 63% and 46%, respectively). Most International Prognostic Score factors were not prognostic on univariate analyses, whereas Cox multivariate regression identified 2 risk factors associated with inferior overall survival: (1) age more than 70 years (2.24; 95% CI, 1.16-4.33, P = .02) and (2) loss of activities of daily living (2.71; 95% CI, 1.07-6.84, P = .04). Furthermore, a novel survival model based on number of these risk factors (0, 1, or 2) showed differential 2-year OS of 83%, 70%, and 13%, respectively (P < .0001) and 5-year OS of 73%, 51%, and 0%, respectively (P < .0001).

Analysis of very elderly (≥80 years) non-hodgkin lymphoma: impact of functional status and co-morbidities on outcome.

Data on outcome, prognostic factors, and treatment for very elderly non‐Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients ≥80 years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily living (ADLs), and co‐morbidities using the Cumulative Illness Rating Scale‐Geriatrics (CIRS‐G). We identified 303 patients: 170 aggressive NHL (84% B cell/16% T cell) and 133 indolent NHL (82% B cell/18% T cell). Median age was 84 years (80–95). A geriatric syndrome was present in 26% of patients, 18% had ≥1 grade 4 CIRS‐G, and 14% had loss of ADLs. At 49‐month median follow‐up, 4‐year progression‐free (PFS) and overall survival (OS) for aggressive NHLs were 31% and 44% respectively (stage I/II: PFS 53% and OS 66%; stage III/IV: PFS 20% and OS 32%; P < 0·0001 and 0·0002, respectively). Four‐year PFS and OS for indolent NHL were 44% and 66% respectively, regardless of stage. Multivariate regression analysis identified two key factors that predicted inferior PFS and OS for both NHL groups: lack of CR and loss of ADLs. Prospective studies for very elderly NHL that incorporate geriatric tools, especially ADLs, are warranted.

The Vulnerable Elders Survey-13 Predicts Mortality in Older Adults with Later-Stage Colorectal Cancer Receiving Chemotherapy: A Prospective Pilot Study

To the Editor: Colorectal cancer (CRC) is the second most common cause of cancer death in the Western world. Almost half of all CRC cases occur in individuals aged 70 and older, but the data regarding treatment are largely focused on individuals younger than 65, even though studies suggest that older adults with CRC derive benefit from adjuvant chemotherapy equivalent or nearly equivalent to that of younger individuals. Older adults form a heterogeneous group, and physiological fitness is weakly correlated with chronological age; criteria other than age should help form the basis for treatment decisions. One solution is to derive these criteria using the tools of a comprehensive geriatric assessment (CGA). A prospective cohort study was conducted to evaluate baseline CGA for older adults with Stage III and IV CRC undergoing first-line chemotherapy. It was hypothesized that the presence of impairments on the CGA would be associated with poorer survival. Eligible individuals were recruited from the University of Chicago Gastrointestinal Medical Oncology Clinic between February 2006 and February 2009. Protocol approval was obtained from the institutional review board, and all participants provided written informed consent. Participants underwent assessments just before their first dose of chemotherapy. Survival data were obtained from chart review and the Social Security Death Index. The comprehensive evaluation included the Vulnerable Elders Survey (VES-13), a 13-item self-administered survey designed to screen for overall functional status, and assessments of cognition, emotional affect, social functioning, nutritional status, activities of daily living (ADLs), comorbidities, and physical performance. Bivariate analysis for overall survival used Cox proportional hazards models and Kaplan-Meier curves, and multivariate survival analysis was performed using logistic regression. The initial model was obtained by including Eastern Co-operative Oncology Group Performance Status (ECOG-PS), ADL, and VES-13 scores, all of which were significant (P ≤ .05) in the bivariate analysis, plus age. The models were limited to four variables to avoid overfitting, given the small data set. All statistical calculations were performed using Stata SE, version 11 (StataCorp LP, College Station, TX). Thirty-eight patients were enrolled (median age 72, range 65–89; 63% male). Seventy-nine percent had metastatic disease at presentation. Of the 33 for whom baseline ECOG-PS was assessed, 30 (91%) had a PS of 0 or 1 as assessed according to the treating physician. Bivariate analysis revealed several measures that were associated with poorer overall survival in this cohort. For the entire cohort, VES-13 of 3 or greater (hazard ratio (HR) = 5.34, P = .002), ECOG PS of 1 or greater (HR = 2.4, P = .05), ADL dependence (HR = 5.62, P = .005), and Geriatric Depression Scale (GDS) score of 5 or greater (HR = 3.95, P = .04) were correlated with poorer survival. For individuals with metastatic disease, only VES-13 of 3 of greater (HR = 4.71, P = .005) and ADL dependence (HR = 6.19, P = .01) were prognostic. Using a multivariate regression model, only abnormal VES-13 score remained significant (HR = 15.61, P = .02, Figure 1). Age was not prognostic in the bivariate (HR = 1.02, P = .56 for ≥75 vs <75) or multivariate model. Relative dose intensity of chemotherapy of greater than 85% was also not predictive of overall survival (HR = 0.61, 95% confidence interval = 0.25–1.41). Oncologists are increasingly faced with treatment decisions for older adults, who are much less likely to receive even well-established therapies. This may derive from lack of knowledge about trials that included older adults or concern about the generalizability of trial results from younger cohorts being applied to older adults. Tools such as the VES-13 that formally and prospectively assess vulnerability may help provide important prognostic information. In the current study, baseline VES-13 scores emerged as the best prognostic tool. Competing causes of death are important to consider in this age group, and VES-13 should be incorporated into risk assessments. It adds prognostic information to ECOG-PS, a commonly used assessment of performance status in oncology practice typically used to determine fitness for chemotherapy. The cohort was small and incorporated individuals receiving chemotherapy in addition to surgery and those with metastatic disease, reducing the generalizability of the

Evidence-based guidelines and quality measures in the care of older adults.

Older adults with chronic diseases are often excluded from study populations, so EBM guidelines often do not apply to them.

Old versus frail: why it matters in lymphoma

3741. 8. Peyrade F, Jardin F, Gisselbrecht C, et al. Rituximab and reduced dose CHOP (R-mini-CHOP) for patients over 80 years with diffuse large B-cell lymphoma (DLBCL) Groupe d’Etude Des Lymphomes De l’Adulte (GELA) study LNH037B. Blood 2010;116(Suppl. 1): Abstract 853. 9. Link BK, Brooks J, Wright K, et al. Diffuse large B-cell lymphoma in the elderly: diffusion of treatment with rituximab and survival advances with and without anthracyclines. Leuk Lymphoma 2011;52:994–1002. 10. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146–M156. 11. Repetto L, Fratino L, Audisio R, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 2002;20:494–502. 12. Balducci L, Beghe C. The application of the principles of geriatrics to the management of the older person with cancer. Crit Rev Oncol Hematol 2000;35:147–154. Commentary 939

Characterizing cancer cachexia in the geriatric oncology population

OBJECTIVES Cancer cachexia, characterized by weight loss and sarcopenia, leads to a decline in physical function and is associated with poorer survival. Cancer cachexia remains poorly described in older adults with cancer. This study aims to characterize cancer cachexia in older adults by assessing its prevalence utilizing standard definitions and evaluating associations with components of the geriatric assessment (GA) and survival. MATERIALS AND METHODS Patients with cancer older than 65 years of age who underwent a GA and had baseline CT imaging were eligible in this cross-sectional study. Cancer cachexia was defined by the international consensus definition reported in 2011. Sarcopenia was measured using cross-sectional imaging and utilizing sex-specific cut-offs. Associations between cachexia, sarcopenia, and weight loss with survival and GA domains were explored. RESULTS Mean age of 100 subjects was 79.9 years (66-95) and 65% met criteria for cancer cachexia. Cachexia was associated with impairment in instrumental activities of daily living (IADL) (p = .017); no significant association was found between sarcopenia or weight loss and IADL impairment. Cachexia was significantly associated with poorer survival (median 1.0 vs 2.1 years, p = .011). CONCLUSIONS Cancer cachexia as defined by the international consensus definition is prevalent in older adults with cancer and is associated with functional impairment and decreased survival. Larger prospective studies are needed to further describe cancer cachexia in this population.

Allogeneic transplant for peripheral T-cell lymphoma: a sparkle of hope and many questions

Peripheral T-cell lymphoma (PTCL) comprises a heterogeneous group of diseases with overall aggressive clinical course and dismal prognosis on average [1,2]. For subtypes other than ALK-positive anaplastic large cell lymphoma (ALCL), the application of standard lymphoma regimens (e.g. cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) results in low remission rates and unacceptably high rates of recurrence of progression. Other combinations are under investigation, including those incorporating etoposide and/or alemtuzumab [3,4], but progress is hampered by the relative rarity of PTCL. Given these findings, autologous stem cell transplant (auto-SCT) has been employed as a consolidative therapy, either up-front or at relapse. Several small prospective trials have been completed [5–9] in the front-line setting. Outcomes (progression-free survival [PFS], overall survival [OS]) in some were not substantially different compared to chemotherapy alone. A significant selection bias complicates interpretation in those trials with superior outcomes. Paralleling its application in B-cell non-Hodgkin lymphoma (B-NHL), auto-SCT has been utilized in the relapsed/refractory setting, but outcomes were generally unsatisfactory in retrospective trials [10,11]; no prospective data exist. Allogeneic stem cell transplant (allo-SCT) has also been proposed as a potentially curative therapy for relapsed PTCL, bolstered by optimism for a ‘graftversus-lymphoma’ (GVL) effect. The largest study to date, a retrospective analysis of 77 patients, demonstrated a 5-year OS of 57%, with significant differences in outcomes between T-NHL subtypes: patients with angioimmunoblastic T cell lymphoma (AITL) had the best outcomes (5-year OS, 80%), followed by those with PTCL and ALCL (5-year OS, 58% and 48%, respectively) [12]. Patients achieving a complete or partial response prior to transplant had substantially better OS compared to those who did not (69% vs. 29%, p1⁄4 0.04). These survival numbers are offset by a 33% transplant-related mortality (TRM). Acute graftversus-host disease (GVHD) was an adverse prognostic factor, but the authors posited a GVL effect based on two patients who achieved a second complete response after donor lymphocyte infusion (DLI). A second retrospective study incorporating patients with PTCL reported three patients with a response to DLI [13], but similarly indicated an adverse effect of GVHD as well as a TRM of 42%. This combination of high TRM and purported GVL effect has stimulated interest in reducedintensity conditioning (RIC) allo-SCT. The only prospective trial reported thus far using allo-SCT in PTCL analyzed this approach. Corradini et al. reported a 3-year OS of 81% with a corresponding TRM of only 6% in 17 patients with relapsed PTCL [14]. Additionally, two patients had a response to DLI or withdrawal of immunosuppression. These outcomes are encouraging; however, all patients but one had demonstrated chemosensitivity, challenging the overall applicability of these results in a disease for which attaining a remission remains a major challenge. Moreover, a recent retrospective analysis of 126 patients undergoing allo-SCT found no differences in PFS, OS, or TRM comparing patients