Relevance of different prognostic scores in primary CNS lymphoma in the era of intensified treatment regimens: A retrospective, multicenter analysis of 174 patients.

OBJECTIVES: Treatment intensification (including consolidative high-dose chemotherapy with autologous stem cell transplantation [HDT-ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients. METHODS: We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression-free survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three-factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance. RESULTS: Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT-ASCT. Two-year OS and 2-year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p = .003) and 3F score (p < .001), but not the IELSG score (p = .06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C-index [0.71]) outperformed both the MSKCC (C-index [0.64]) and IELSG (C-index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C-index (0.66). CONCLUSION: The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches.

Myeloid checkpoint blockade improves killing of T-acute lymphoblastic leukemia cells by an IgA2 variant of daratumumab.

Antibody-based immunotherapy is increasingly employed to treat acute lymphoblastic leukemia (ALL) patients. Many T-ALL cells express CD38 on their surface, which can be targeted by the CD38 antibody daratumumab (DARA), approved for the treatment of multiple myeloma. Tumor cell killing by myeloid cells is relevant for the efficacy of many therapeutic antibodies and can be more efficacious with human IgA than with IgG antibodies. This is demonstrated here by investigating antibody-dependent cellular phagocytosis (ADCP) by macrophages and antibody-dependent cell-mediated cytotoxicity (ADCC) by polymorphonuclear (PMN) cells using DARA (human IgG1) and an IgA2 isotype switch variant (DARA-IgA2) against T-ALL cell lines and primary patient-derived tumor cells. ADCP and ADCC are negatively regulated by interactions between CD47 on tumor cells and signal regulatory protein alpha (SIRPα) on effector cells. In order to investigate the impact of this myeloid checkpoint on T-ALL cell killing, CD47 and glutaminyl-peptide cyclotransferase like (QPCTL) knock-out T-ALL cells were employed. QPTCL is an enzymatic posttranslational modifier of CD47 activity, which can be targeted by small molecule inhibitors. Additionally, we used an IgG2σ variant of the CD47 blocking antibody magrolimab, which is in advanced clinical development. Moreover, treatment of T-ALL cells with all-trans retinoic acid (ATRA) increased CD38 expression leading to further enhanced ADCP and ADCC, particularly when DARA-IgA2 was applied. These studies demonstrate that myeloid checkpoint blockade in combination with IgA2 variants of CD38 antibodies deserves further evaluation for T-ALL immunotherapy.

An evidence-based determination of issues affecting quality of life and patient-reported outcomes in lung cancer: results of a survey of 660 patients.

INTRODUCTION: Identifying issues of importance for patients with lung cancer is critical in individualizing care and developing effective quality of life instruments based on evidence. This study was conducted to provide enhanced content validity for measures assessing quality of life and patient-reported outcomes (PROs). METHODS: We conducted an anonymous, cross-sectional, electronic web-based survey of 660 lung cancer patients. The survey asked patients to rank 20 quality of life issues on a 5-point scale ranging from "not important at all" to "very important". Analysis was obtained using key factors such as stage of disease, performance status, and gender. RESULTS: The survey was completed by 297 males and 363 females (median age 62 years). The top five rated issues were: quality of life, maintaining independence, ability to perform normal activities, ability to sleep, and not being fatigued. The issues of importance were all ranked, using the two highest categories ("very important" and "important") by at least 90% of patients. Although symptoms are important to patients, they were not the most highly ranked issues of concern; instead, global issues illustrating the effect of the symptoms on the patient, such as quality of life, maintaining independence, and performing normal activities were ranked highest. CONCLUSIONS: This is the largest analysis of evidence-based data determining content validity for quality of life and PROs as indicated by patients. These results provide greater confidence that the content of lung cancer quality of life measures is appropriate. In addition, the survey clearly demonstrates that PRO measures that only evaluate symptoms are not fully responding to patient-expressed needs.

Patient income level and cancer clinical trial participation.

PURPOSE: Studies have shown an association between socioeconomic status (SES) and quality of oncology care, but less is known about the impact of patient SES on clinical trial participation. PATIENTS AND METHODS: We assessed clinical trial participation patterns according to important SES (income, education) and demographic factors in a large sample of patients surveyed via an Internet-based treatment decision tool. Logistic regression, conditioning on type of cancer, was used. Attitudes toward clinical trials were assessed using prespecified items about treatment, treatment tolerability, convenience, and cost. RESULTS: From 2007 to 2011, 5,499 patients were successfully surveyed. Forty percent discussed clinical trials with their physician, 45% of discussions led to physician offers of clinical trial participation, and 51% of offers led to clinical trial participation. The overall clinical trial participation rate was 9%. In univariate models, older patients (P = .002) and patients with lower income (P = .001) and education (P = .02) were less likely to participate in clinical trials. In a multivariable model, income remained a statistically significant predictor of clinical trial participation (odds ratio, 0.73; 95% CI, 0.57 to 0.94; P = .01). Even in patients age ≥ 65 years, who have universal access to Medicare, lower income predicted lower trial participation. Cost concerns were much more evident among lower-income patients (P < .001). CONCLUSION: Lower-income patients were less likely to participate in clinical trials, even when considering age group. A better understanding of why income is a barrier may help identify ways to make clinical trials better available to all patients and would increase the generalizability of clinical trial results across all income levels.

Influence of tumor type, disease status, and patient age on self-reported interest regarding participation in cancer clinical trials.

There is limited information available regarding the reasons cancer patients decide to enter clinical trials. To explore this issue, aggregate responses to the question, "Are you interested in learning about clinical trials for your condition?" obtained from >115,000 cancer patients (or their families) who entered data into 1 of several proprietary decision-support programs embedded within approximately 100 well-established cancer-related Internet sites were analyzed. The percentage of patients (or their families) who expressed interest in learning about clinical trials ranged from as low as 21% (endometrial and cervix cancer patients >80 years of age; n=178) to as high as 85% (recurrent ovarian cancer patients, age 51-60; n=842). Patients >80 years of age, regardless of sex, tumor type, or status of disease, were considerably less likely to be interested in clinical trial information than younger individuals. Whereas there were no differences between males and females in their desire to obtain information, patients with self-declared more "serious conditions" (e.g., metastatic breast cancer, recurrent prostate cancer), and those with specific cancers having a widely recognized poor prognosis (e.g., nonsmall cell lung cancer), were more likely to request study information. In the current evaluation of a large database of individuals who elected to participate in 1 of several cancer-related decision-support programs, major differences in self-expressed interest in obtaining information regarding clinical trials was observed. Particularly notable was the reduced desire to gather such information among the very elderly, and the increased interest by patients with the most serious cancer-related conditions.

Profile of ovarian cancer patients seeking information from a web-based decision support program.

BACKGROUND: There is limited information available regarding the characteristics of patients who elect to gather and share information about their malignancy on the Internet. METHODS: Using a proprietary decision support program embedded into a number of established websites, individuals entered personal clinical data into disease site profilers designed to provide information about evidence-based treatment options, based on specific characteristics (e.g., stage of disease, prior therapy) provided by the patients. The aggregate data were evaluated to examine the characteristics of patients with gynecological cancer (with a focus on newly diagnosed and recurrent ovarian cancer) using such a tool. RESULTS: From early 2000 through November 2004, >15,000 patients with gynecological cancer have entered data into one of four profilers: newly diagnosed (n = 5604)/recurrent (n = 2803) ovarian, endometrial, and cervical cancers. Internal data consistency includes similar ages and general health histories of the ovarian and endometrial cancer populations and younger age of the cervical cancer patients. Whereas 90% of the women with ovarian cancer considered themselves to be in "good health," 64% of newly diagnosed vs. only 50% of recurrent disease patients declared their activity level was "normal." Of the recurrent patients, 32% stated they had undergone a secondary surgery. The overall aggressive management philosophy of the recurrent patients in this series is supported by the observation that 33% had received > or =4 prior chemotherapy regimens, 97% desired additional treatment, and 81% were interested in clinical trials. CONCLUSIONS: Women with ovarian cancer seeking assistance from web-based decision support programs may represent a subgroup with unique clinical features compared with the general patient population.

Clinical features of American versus non-American gynecologic cancer patients requesting information from a proprietary web-based decision-support program.

PURPOSE: As the Internet can potentially substantially reduce geographic barriers to the dissemination of health-related information, it would be interesting to know if non-American women with gynecologic malignancies accessing United States (US)-based cancer Web sites differ from American patients with the same illness. PATIENTS AND METHODS: Aggregate data from individuals providing personal clinical information into one of four proprietary gynecologic cancer (cervix, endometrial, newly diagnosed and recurrent ovarian cancers) decision-support programs (NexProfiler Treatment Option Tools for Cancer; NexCura Inc., Seattle WA, USA) currently embedded within approximately 100 established cancer-related Web sites were examined for differences between American versus non-American patient populations. RESULTS: In this analysis, which included >15,000 patients, American and non-American gynecologic cancer patients were remarkably similar in most clinical characteristics, including age, stage of disease at presentation, overall health, and desire to receive information regarding clinical trials. Notable differences included features suggestive of a more aggressive surgical philosophy in the US (e.g., higher percentage of American recurrent ovarian cancer patients reported they had undergone a secondary surgical procedure; greater use of radiotherapy in non-American cervical cancer patients). CONCLUSION: Despite differences in geographic location and health care delivery systems, American and non-American patients with gynecologic malignancies and with access to Internet-based cancer information exhibit few, but notable, differences in self-reported clinical characteristics.

An examination of characteristics of lung and colon cancer patients participating in a web-based decision support program. Internet-based decision support programs.

OBJECTIVES: Little is known about the characteristics of cancer patients who employ the Internet as a technique to gather information to assist them in their management. METHODS: To address this issue, aggregate data from individuals with colon (n=7,543), non-small cell lung (n=24,778) and small cell lung (n=13,817) cancers who provided personal clinical information through participation in a proprietary Web-based decision support program (NexProfiler Treatment Option Tools for Cancer; NexCura, Inc., Seattle, Wash., USA) were evaluated for potential differences between specific patient subgroups. RESULTS: Examination of a number of objective (e.g., prior therapy) and subjective (e.g., overall health, activity level) parameters failed to reveal any major differences based on sex, geographical location (US vs. non-US) or newly diagnosed versus recurrent disease (non-small cell lung cancer patients). Several notable findings included: (1) overall >65% of colon cancer patients and >70% of lung cancer patients stated that they 'were interested in learning about clinical trials'; (2) 65-70% of patients with recurrent non-small cell lung cancer stated that their 'general health was good', while >60% noted they had symptoms and >50% declared their activity level to be essentially 'normal'; (3) while almost 80% of small cell lung cancer patients noted symptoms, >60% stated their activity level was 'normal'. CONCLUSION: These data suggest that the population of patients who seek information from Web-based decision support programs share a number of relevant clinical features, yet they appear to represent a unique subset among all individuals with malignant disease. It will be important for oncologists to more fully understand the objectives of this population in order to assist such patients (and their families) in their use of this remarkably powerful, but essentially unregulated, technology.