High-dose Methotrexate and Rituximab Induction Regimen In Immunocompetent Patients With Primary CNS Lymphoma: A Retrospective Single-Center Study of Survival Predictors

Purpose:Primary Central Nervous System Lymphoma (PCNSL) is an aggressive tumor that is confined to the CNS. Although the provision of high-dose methotrexate (HD-MTX) has remarkably improved outcomes in PCNSL patients, the optimal treatment regimens and standard MTX dose have been largely controversial. Herein, we sought to explore the impact of adjuvant Rituximab and different dosages of HD-MTX on survival outcomes of immunocompetent patients with PCNSL.Methods:In this study, we examined patients with PCNSL treated at a single NCI-designated comprehensive cancer center to evaluate their survival outcomes. We conducted a retrospective analysis of 51 immunocompetent patients with PCNSL who received their induction chemotherapy at the University of Alabama at Birmingham (UAB) between 2001 and 2019. Only adult patients with a confirmed diagnosis of PCNSL who had either HD-MTX alone or in combination with Rituximab were included. Patients’ demographics, clinical characteristics, and survival data were collected and analyzed.Results:There is no significant difference in survival among patients who received MTX alone versus MTX plus Rituximab. Furthermore, lower doses of MTX were associated with worse survival outcomes; however, this difference in survival was not significant when adjusted to age.Conclusion:Our experience challenges the role of Rituximab in PCNSL during induction therapy. Our study also highlights the shorter survival in elderly patients with PCNSL which can be related, to some extent, to the relatively lower doses of HD-MTX. There is an unmet need to establish a consensus on the most effective upfront regimen in PCNSL through prospective studies.

Demographic and Clinical Predictors of Engaging in Tobacco Cessation Counseling at a Comprehensive Cancer Center

PURPOSE: To address challenges promoting tobacco cessation in oncology settings, it is important to understand characteristics associated with patient engagement in tobacco cessation treatment. This analysis examined predictors of participating in at least one tobacco cessation counseling session among patients referred to a comprehensive cancer center's Tobacco Intervention and Psychosocial Support (TIPS) service. METHODS: Patients with cancer who reported current smoking or recently quitting and referred to TIPS between June 2017 and February 2020 were included in the analysis. Independent variables included sex, race and ethnicity, insurance type, cancer diagnosis (tobacco-related or not), age, nicotine dependence, and cigarettes smoked per day at baseline. The outcome variable was completion of at least one tobacco cessation counseling session among those assessed by the TIPS program. Unadjusted and adjusted analyses tested associations between the independent variables and tobacco cessation counseling engagement. RESULTS: Of 360 oncology patients referred to the TIPS program, 224 (62.2%) were assessed and 120 (33%) engaged in at least one counseling session. After controlling for sociodemographics and tobacco use, the results demonstrated that patients diagnosed with tobacco-related cancers were 45.3% less likely to engage in the tobacco cessation program compared with those with non–tobacco-related cancers ( P = .041). CONCLUSION: Patients diagnosed with tobacco-related cancers were less likely to engage in TIPS. Additional therapeutic resources may be needed to engage these patients to address potential explanatory factors, such as stigma, guilt, and fatalism. More research is needed to explore the impact of a tobacco-related cancer diagnosis on treatment engagement.

Genomic Landscape of Lymphatic Malformations: A Case Series and Response to the PI3Kα Inhibitor Alpelisib in an N-of-One Clinical Trial

ABSTRACTBackgroundLymphatic malformations (LMs) often pose treatment challenges due to a large size or a critical location that could lead to disfigurement, and there are no standardized treatment approaches for either refractory or unresectable cases.MethodsWe examined the genomic landscape of a patient cohort of LMs (n=30 cases) that underwent comprehensive genomic profiling (CGP) using a large-panel next generation sequencing (NGS) assay. Immunohistochemical analyses were completed in parallel.ResultsThese LMs had low mutational burden with hotspot PIK3CA mutations and NRAS mutations being most frequent, and mutually exclusive. All LM cases with Kaposi sarcoma-like (kaposiform) histology had NRAS mutations. One index patient presented with subacute abdominal pain and was diagnosed with a large retroperitoneal lymphatic malformation harboring a somatic PIK3CA gain-of-function mutation (H1047R). The patient achieved a rapid and durable complete response to the PI3Kα inhibitor alpelisib within the context of a personalized N-of-1 clinical trial (NCT03941782). In translational correlative studies, canonical PI3Kα pathway activation was confirmed by immunohistochemistry and human LM-derived lymphatic endothelial cells carrying an allele with an activating mutation at the same locus were sensitive in vitro to alpelisib in a concentration-dependent manner.ConclusionsOur findings establish that LM patients with conventional or kaposiform histology have distinct, yet targetable, driver mutations.FundingR.P. and W.A. are supported by awards from the Levy-Longenbaugh Fund. S.G. is supported by awards from the Hugs for Brady Foundation. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of Arizona Cancer Center (CA023074), the University of New Mexico Comprehensive Cancer Center (CA118100), and the Rutgers Cancer Institute of New Jersey (CA072720). B.K.M. was supported by National Science Foundation via Graduate Research Fellowship DGE-1143953.Clinical trial numberNCT03941782

Struggling With Extensive Informed Consent Procedures for Cancer Trails – Is There Even a Benefit for the Patients?

PurposeInformed consent procedures in clinical trials often differ in length and complexity to those in clinical routine care. Little is known about the benefit of extensive procedures as intended in clinical trials compared to procedures in routine cancer treatment. MethodsIn two different clinical studies performed at a comprehensive cancer center, we compared patients’ comprehension and satisfaction of current informed consent procedures in routine clinical care with the level of comprehension and satisfaction of patients treated within clinical trials. Patients with a new cancer diagnosis and recent informed consent received a questionnaire about satisfaction, comprehension, time management and physician-patient relationship of the informed consent process. Patients in cohort 1 consented to cancer treatment within a clinical trial and were additionally interviewed in a structured way; patients in cohort 2 consented to “standard” chemotherapy and received a follow-up questionnaire after 6 months. ResultsIn cohort 1, 82 patients completed the questionnaire and had an additional structured interview. They were treated in 41 different trials, receiving up to 40 pages of educational material. In cohort 2, 89 patients completed the first and 52 completed the follow-up questionnaire after receiving a standard informed consent form of 6 pages. Subjective understanding and satisfaction with the information provided was equally very high. However, deficits in objective understanding were observed in both cohorts. ConclusionExtensive informed consent procedures for clinical cancer trials have not been associated with a higher level of satisfaction or measurable objective understanding, therefore the benefit seems to be limited.

Urologic Oncology Patient Perspectives During COVID-19 Treatment Delays

Purpose The COVID-19 pandemic led to delays in urologic cancer treatment. We sought the patient perspective on these delays. Methods We conducted a mixed methods study with an explanatory-sequential design. Survey findings are presented here. Patients from a Midwestern Comprehensive Cancer Center and the Bladder Cancer Advocacy Network provided demographic and clinical data and responded to statements asking them to characterize their experience of treatment delay, patient-provider communication and coping strategies. We quantified patient distress with an ordinal scale (0-10), based on the National Comprehensive Cancer Network Distress Thermometer (NCCN-DT). Results Forty-four consenting patients responded to the survey. Most were older than 61 years (77%) and male (66%). Their diagnoses included bladder (45%), prostate (30%) and kidney (20%) cancers. Median time since diagnosis was 6 months, 95% had plans for surgical treatment. Dominant reactions to treatment delay included fear that cancer would progress (50%) and relief at avoiding COVID-19 exposure (43%). Most patients reported feeling that their providers acknowledged their emotions (70%), yet 52% did not receive follow up phone calls and only 55% felt continually supported by their providers. Patients’ median distress level was 5/10 with 68% of patients reaching a clinically significant level of distress (≥4). Thematically grouped suggestions for providers included better communication (18%), more personalized support (14%), and better patient education (11%). Conclusion During the COVID-19 pandemic, a high proportion of urologic cancer patients reached a clinically significant level of distress. While they felt concern from providers, they desired more engagement and personalized care.