Clonal hematopoiesis in patients with HIV and cancer.

BACKGROUND: Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. METHODS: We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks. RESULTS: In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, p=0.07). After adjusting for patient characteristics, PWH were four-times more likely to have CH than PWoH (OR 4.1, 95% CI 1.3-13.9, p=0.02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH). CONCLUSION: This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.

CML in the very elderly: the impact of comorbidities and TKI selection in a real-life multicenter study.

Tyrosine kinase inhibitors (TKIs) have greatly improved chronic myeloid leukemia (CML) treatments, with survival rates close to the general population. Yet, for the very elderly, robust data remains limited. This study focused on assessing comorbidities, treatment approaches, responses, and survival for elderly CML patients. Our study was conducted on 123 elderly (≥ 75 years) CML patients across four centers in Israel and Moffitt Cancer Center, USA. The median age at diagnosis was 79.1 years, with 44.7% being octogenarians. Comorbidities were very common; cardiovascular risk factors (60%), cardiovascular diseases (42%), with a median age-adjusted Charlson Comorbidity Index (aaCCI) of 5. Imatinib was the leading first-line therapy (69%), while the use of second-generation TKIs increased post-2010. Most patients achieved a major molecular response (MMR, 66.7%), and half achieved a deep molecular response (DMR, 50.4%). Over half (52.8%) of patients moved to second-line, and nearly a quarter (23.5%) to third-line treatments, primarily due to intolerance. Overall survival (OS) was notably longer in patients with an aaCCI score below 5, and in patients who attained DMR. Contrary to expectations, the Israeli cohort showed a shorter actual life expectancy than projected, suggesting a larger impact of CML on elderly survival. In summary, imatinib remains the main initial treatment, but second-generation TKIs are on the rise among elderly CML patients. Outcomes in elderly CML patients depend on comorbidities, TKI type, response, and age, underscoring the need for personalized therapy and additional research on TKI effectiveness and safety.

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study.

BACKGROUND: Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes. METHODS: Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve. RESULTS: Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001-.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001-.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001-.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors. CONCLUSION: Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.

Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.

BACKGROUND: Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. METHODS: Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. RESULTS: Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates. CONCLUSIONS: Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.

Oncogeriatric Developments.

Cancer is a disease of aging and is rapidly becoming the number one cause of mortality in older people. Over their lifetime, one in two men and one in three women will develop a cancer, with half of the risk being beyond the age of seventy. Therefore, cancer is a problem frequently encountered by geriatricians. In this article, we review a few recent progresses that will be of interest to the geriatric community. First, we now have robust evidence that a comprehensive geriatric assessment and management change outcomes in older cancer patients, notably allowing decreased treatment toxicity, better treatment completion, and increased functional outcomes. In gastrointestinal cancers and breast cancer, several recent studies have addressed when treatment intensity can be decreased, and when it cannot. New treatments for acute myeloid leukemia are finally beginning to improve outcomes for older patients and such patients should be referred to oncologists for management. In prostate cancer, new imaging techniques (e.g., PSMA scan) and treatment options can allow better treatment targeting and spare some hormonal and chemotherapy toxicity. Finally, we review recent public policy efforts to address the epidemiologic wave of cancer in older patients on a global scale.

Metagenomics and chemotherapy-induced nausea: A roadmap for future research.

Uncontrolled chemotherapy-induced nausea and vomiting can reduce patients' quality of life and may result in premature discontinuation of chemotherapy. Although nausea and vomiting are commonly grouped together, research has shown that antiemetics are clinically effective against chemotherapy-induced vomiting (CIV) but less so against chemotherapy-induced nausea (CIN). Nausea remains a problem for up to 68% of patients who are prescribed guideline-consistent antiemetics. Despite the high prevalence of CIN, relatively little is known regarding its etiology independent of CIV. This review summarizes a metagenomics approach to the study and treatment of CIN with the goal of encouraging future research. Metagenomics focuses on genetic risk factors and encompasses both human (ie, host) and gut microbial genetic variation. Little work to date has focused on metagenomics as a putative biological mechanism of CIN. Metagenomics has the potential to be a powerful tool in advancing scientific understanding of CIN by identifying new biological pathways and intervention targets. The investigation of metagenomics in the context of well-established demographic, clinical, and patient-reported risk factors may help to identify patients at risk and facilitate the prevention and management of CIN.

Impact of taxane-based chemotherapy among older women with breast cancer on cognition and quality of life: a longitudinal pooled analysis.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data were pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36 months after. Cognitive performance was assessed with objective (working memory, processing speed, and executive functions) and subjective tests and physical, emotional, and functional well-being were also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36 months. Measures of well-being improved from prior to systemic therapy to 12 months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study.

PURPOSE: Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of cognition prior to adjuvant therapy and tumor aggressivity in older breast cancer patients. METHODS: Women diagnosed with non-metastatic breast cancer (n = 705) ages 60-98 were enrolled from August 2010-March 2020. Cognition was measured post-surgery, pre-systemic therapy using self-reported (FACT-Cog Perceived Cognitive Impairment [PCI]) and objective tests of attention, processing speed, and executive function (APE domain) and learning and memory [LM domain]. Linear regression tested associations of pre-treatment tumor features and cognition, adjusting for age, race, and study site. HER2 positivity and higher stage (II/III vs. 0/I) were a priori predictors of cognition; in secondary analyses we explored associations of other tumor features and cognitive impairment (i.e., PCI score < 54 or having 2 tests < 1.5 SD or 1 test < 2 SD from the mean APE or LM domain score). RESULTS: HER2 positivity and the hormone receptor negative/HER2 + molecular subtype were associated with lower adjusted mean self-reported cognition scores and higher impairment rates (p values < .05). Higher stage of disease was associated with lower objective performance in APE. Other tumor features were associated with cognition in unadjusted and adjusted models, including larger tumor size and lower PCI scores (p = 0.02). Tumor features were not related to LM. CONCLUSIONS: Pre-adjuvant therapy cognition was associated with HER2 positivity and higher stage of disease and other features of aggressive tumors. Additional research is needed to confirm these results and assess potential mechanisms and clinical management strategies.

Diet quality indices and changes in cognition during chemotherapy.

PURPOSE: No evidence-based prevention strategies currently exist for cancer-related cognitive decline (CRCD). Although patients are often advised to engage in healthy lifestyle activities (e.g., nutritious diet), little is known about the impact of diet on preventing CRCD. This secondary analysis evaluated the association of pre-treatment diet quality indices on change in self-reported cognition during chemotherapy. METHODS: Study participants (n = 96) completed the Block Brief Food Frequency Questionnaire (FFQ) before receiving their first infusion and the PROMIS cognitive function and cognitive abilities questionnaires before infusion and again 5 days later (i.e., when symptoms were expected to be their worst). Diet quality indices included the Dietary Approaches to Stop Hypertension (DASH), Alternate Mediterranean Diet (aMED), and a low carbohydrate diet index and their components. Descriptive statistics were generated for demographic and clinical variables and diet indices. Residualized change models were computed to examine whether diet was associated with change in cognitive function and cognitive abilities, controlling for age, sex, cancer type, treatment type, depression, and fatigue. RESULTS: Study participants had a mean age of 59 ± 10.8 years and 69% were female. Although total diet index scores did not predict change in cognitive function or cognitive abilities, higher pre-treatment ratio of aMED monounsaturated/saturated fat was associated with less decline in cognitive function and cognitive abilities at 5-day post-infusion (P ≤ .001). CONCLUSIONS: Higher pre-treatment ratio of monounsaturated/saturated fat intake was associated with less CRCD early in chemotherapy. Results suggest greater monounsaturated fat and less saturated fat intake could be protective against CRCD during chemotherapy.

Priorities for the global advancement of care for older adults with cancer: an update of the International Society of Geriatric Oncology Priorities Initiative.

In 2011, the International Society of Geriatric Oncology (SIOG) published the SIOG 10 Priorities Initiative, which defined top priorities for the improvement of the care of older adults with cancer worldwide.1 Substantial scientific, clinical, and educational progress has been made in line with these priorities and international health policy developments have occurred, such as the shift of emphasis by WHO from communicable to non-communicable diseases and the adoption by the UN of its Sustainable Development Goals 2030. Therefore, SIOG has updated its priority list. The present document addresses four priority domains: education, clinical practice, research, and strengthening collaborations and partnerships. In this Policy Review, we reflect on how these priorities would apply in different economic settings, namely in high-income countries versus low-income and middle-income countries. SIOG hopes that it will offer guidance for international and national endeavours to provide adequate universal health coverage for older adults with cancer, who represent a major and rapidly growing group in global epidemiology.

Impact of age, comorbidity, and treatment characteristics on survival in older women with advanced high grade epithelial ovarian cancer.

OBJECTIVES: Older women have a worse prognosis with advanced epithelial ovarian cancer (EOC) and comorbidities likely contribute to poor outcomes. We sought to identify comorbid conditions and treatment-related factors in older women. METHODS: A retrospective chart review identified 351 patients who underwent cytoreductive surgery (CRS). 100/351 (28.5%) were ≥ 70 years old. Demographic and clinicopathologic information was collected. Crude progression-free (PFS) and overall survival (OS) estimates were calculated using Kaplan-Meier method. Cox proportional hazards regression model was used to estimate hazard ratios and adjustments for confounders. RESULTS: Study subjects ≥70 years old had significantly: higher Cumulative Illness Rating Scale-Geriatric (CIRS-G) score (5.9 vs 4.3; p = 0.0001), less completion of adjuvant chemotherapy (24% vs 15.1%; p = 0.049), less intraperitoneal (IP) therapy (18.2% vs 35.5%; p = 0.002), less clinical trial participation (16% vs 26.3%; p = 0.040), decreased platinum sensitivity (60% vs 73.7%; p = 0.012) and lacked BRCA mutations (0% vs 12%; p = 0.0006). They were less likely to have optimal CRS (75% vs 86.9%; p = 0.007) with same surgical complexity (p = 0.89). Patients ≥70 had significantly worse PFS and OS. In a multivariate analysis, better OS was associated with younger age (<70 years old), any IP therapy, completion of adjuvant chemotherapy, and platinum sensitivity. CONCLUSION: The older cohort had worse CIRS-G scores (5.9 vs 4.3; p = 0.0001), but no strong associations between comorbidities and treatment characteristics, but less optimal CRS rates (75% vs 86.9%; p = 0.007) with similar surgical complexity and less platinum sensitivity. Our results show comorbid conditions in older patients with advanced EOC may have less impact than tumor biology.

NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study.

BACKGROUND: Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS: The authors report on 36-month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS: All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P < .001). The burden score was related to physical, emotional, and functional well-being (eg, survivors with lower vs higher burden scores had 12.4-point higher physical well-being scores). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (P < .005). CONCLUSIONS: Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than in comparable noncancer populations, suggesting the need for surveillance and opportunities for intervention.

Early stage breast cancer treatment and outcome of older patients treated in an oncogeriatric care and a standard care setting: an international comparison.

INTRODUCTION: Since older patients with breast cancer are underrepresented in clinical trials, an oncogeriatric approach is advocated to guide treatment decisions. However, the effect on outcomes is unclear. The aim of this study was to compare treatments and outcomes between patients treated in an oncogeriatric and a standard care setting. METHODS: Patients aged ≥ 70 years with early stage breast cancer were included. The oncogeriatric cohort comprised unselected patients from the Moffitt Cancer Center, and the standard cohort patients from a Dutch population-based cohort. Cox models were used to characterize the influence of care setting on recurrence risk and overall mortality. RESULTS: Overall, 268 patients were included in the oncogeriatric and 1932 patients in the standard cohort. Patients in the oncogeriatric cohort were slightly younger, had more comorbidity, and received more adjuvant endocrine therapy and chemotherapy. Oncogeriatric care was associated with a lower risk of recurrence, which remained significant after adjustment for patient and tumour characteristics [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.44-0.99]. Oncogeriatric care was also associated with a lower overall mortality, which also remained significant after adjustment for patient and tumour characteristics (HR 0.69, 95% CI 0.55-0.87). CONCLUSIONS: Patients treated in the oncogeriatric care setting had a lower risk of recurrence, which may be explained by more systemic treatment. Overall mortality was also lower, but other explanations besides care setting could not be ruled out as the cohorts had different patient profiles. Future studies need to clarify the impact of an oncogeriatric approach on outcomes.

Clinical Factors and Outcomes of Octogenarians Receiving Curative Surgery for Esophageal Cancer.

BACKGROUND: The incidence of esophageal cancer is increasing in the United States. Although neoadjuvant therapy (NAT) for locally advanced cancers followed by surgical resection is the standard of care, there are no clearly defined guidelines for patients aged ≥79 y. METHODS: Query of an institutional review board-approved database of 1031 esophagectomies at our institution revealed 35 patients aged ≥79 y from 1999 to 2017 who underwent esophagectomy. Age, gender, tumor location, histology, clinical stage, Charlson Comorbidity Index (CCI), NAT administration, pathologic response rate to NAT, surgery type, negative margin resection status, postoperative complications, postoperative death, length of stay, 30- and 90-d mortality, and disease status parameters were analyzed in association with clinical outcome. RESULTS: The median age of the octogenarian cohort was 82.1 y with a male preponderance (91.4%). American Joint Committee on Cancer clinical staging was stage I for 20% of patients, stage II for 27% of patients, and stage III for 50% of patients, which was not statistically significant compared with the younger cohort (P = 0.576). Within the octogenarian group, 54% received NAT compared with 67% in the younger group (P = 0.098). There was no difference in postoperative complications (P = 0.424), postoperative death (P = 0.312), and recurrence rate (P = 0.434) between the groups. However, CCI was significantly different between the octogenarian and nonoctogenarian cohort (P = 0.008), and octogenarians had shorter overall survival (18 versus 62 mo, P<0.001). None of the other parameters assessed were associated with clinical outcomes. CONCLUSIONS: Curative surgery is viable and safe for octogenarians with esophageal cancer. Long-term survival was significantly shorter in the octogenarian group, suggesting the need for better clinical selection criteria for esophagectomy after chemoradiation and that identification of complete responders for nonoperative management is warranted.

Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype.

BACKGROUND: Sleep disturbance and genetic profile are risks for cognitive decline in noncancer populations, yet their role in cancer-related cognitive problems remains understudied. This study examined whether sleep disturbance was associated with worse neurocognitive outcomes in breast cancer survivors and whether sleep effects on cognition varied by genotype. METHODS: Newly diagnosed female patients (n = 319) who were 60 years old or older and had stage 0 to III breast cancer were recruited from August 2010 to December 2015. Assessments were performed before systemic therapy and 12 and 24 months later. Neuropsychological testing measured attention, processing speed, executive function, learning, and memory; self-perceived cognitive functioning was also assessed. Sleep disturbance was defined by self-report of routine poor or restless sleep. Genotyping included APOE, BDNF, and COMT polymorphisms. Random effects fluctuation models tested associations of between-person and within-person differences in sleep, genotype, and sleep-genotype interactions and cognition and controlled for age, reading level, race, site, and treatment. RESULTS: One-third of the patients reported sleep disturbances at each time point. There was a sleep-APOE ε4 interaction (P = .001) in which patients with the APOE ε4 allele and sleep disturbances had significantly lower learning and memory scores than those who were APOE ε4-negative and without sleep disturbances. There was also a sleep disturbance-COMT genotype interaction (P = .02) in which COMT Val carriers with sleep disturbances had lower perceived cognition than noncarriers. CONCLUSIONS: Sleep disturbance was common and was associated with worse cognitive performance in older breast cancer survivors, especially those with a genetic risk for cognitive decline. Survivorship care should include sleep assessments and interventions to address sleep problems.

A Phase II Trial of Selinexor (KPT-330) for Metastatic Triple-Negative Breast Cancer.

LESSONS LEARNED: Single-agent selinexor has limited activity in heavily pretreated patients with metastatic triple-negative breast cancer.Selinexor 60 mg by mouth twice weekly was generally well tolerated with a side-effect profile consistent with previous clinical trials.Future studies of selinexor in this population should focus on combination approaches and a biomarker-driven strategy to identify patients most likely to benefit. BACKGROUND: This phase II trial evaluated the safety, pharmacodynamics, and efficacy of selinexor (KPT-330), an oral selective inhibitor of nuclear export (SINE) in patients with advanced triple-negative breast cancer (TNBC). METHODS: This phase II trial was designed to enroll 30 patients with metastatic TNBC. Selinexor was given at 60 mg orally twice weekly on days 1 and 3 of each week, three of each 4-week cycle. The primary objective of this study was to determine the clinical benefit rate (CBR), defined as complete response + partial response + stable disease (SD) ≥12 weeks. RESULTS: Ten patients with a median age of 60 years (range 44-71 years) were enrolled between July 2015 and January 2016. The median number of prior chemotherapy lines was 2 (range 1-5). A planned interim analysis for the first stage per protocol was performed. Three patients had SD and seven had progressive disease. On the basis of these results and predefined stoppage rules, the study was halted. CONCLUSION: Selinexor was fairly well tolerated in patients with advanced TNBC but did not result in objective responses. However, clinical benefit rate was 30%, and further investigation of selinexor in this patient population should focus on combination therapies.

Improving the quality of survivorship for older adults with cancer.

In May 2015, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging through a U13 grant, convened a conference to identify research priorities to help design and implement intervention studies to improve the quality of life and survivorship of older, frailer adults with cancer. Conference attendees included researchers with multidisciplinary expertise and advocates. It was concluded that future intervention trials for older adults with cancer should: 1) rigorously test interventions to prevent the decline of or improve health status, especially interventions focused on optimizing physical performance, nutritional status, and cognition while undergoing cancer treatment; 2) use standardized care plans based on geriatric assessment findings to guide targeted interventions; and 3) incorporate the principles of geriatrics into survivorship care plans. Also highlighted was the need to integrate the expertise of interdisciplinary team members into geriatric oncology research, improve funding mechanisms to support geriatric oncology research, and disseminate high-impact results to the research and clinical community. In conjunction with the 2 prior U13 meetings, this conference provided the framework for future research to improve the evidence base for the clinical care of older adults with cancer. Cancer 2016;122:2459-68. © 2016 American Cancer Society.

NCCN Guidelines Insights: Older Adult Oncology, Version 2.2016.

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.

Chemotoxicity recurrence in older patients: Risk factors and effectiveness of preventive strategies-a prospective study.

BACKGROUND: The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) and adjustment rules after severe toxicity are derived by consensus, but to the authors' knowledge little is known regarding the determinants of toxicity recurrence, especially in the elderly. METHODS: The authors prospectively accrued 200 patients (aged ≥65 years) before chemotherapy. For those with CTCAE grade 3 to 4 nonhematologic or CTCAE grade 4 hematologic toxicities (severe toxicity), the duration and functional impact, treatment modifications, and severe toxicity recurrence were recorded. The regimen's toxicity was adjusted with the MAX2 index, the average of the most frequent grade 4 hematologic toxicities and the most frequent grade 3 to 4 nonhematologic toxicities reported in publications of a regimen. RESULTS: The median patient age was 73 years (range, 65-90 years). Among 163 patients who were evaluable for toxicity after ≥1 treatment cycle (receiving on average 4.73 cycles), 82 had severe toxicity, 10 were discontinued for toxicity, 6 were discontinued for other reasons, and 5 patients had died. Sixty-one patients received further chemotherapy: 41 without dose modification (16 with secondary prevention measures) and 20 with dose modifications. Without modification, 19 patients (46%) experienced toxicity recurrence (0 deaths). With modification, 7 patients (35%) experienced a toxicity recurrence (1 death). On univariate analysis, treatment intent, hospitalization, duration-adjusted activities of daily living (ADL), quality of life impact, and fatigue were associated with dose modification. ADL remained associated on multivariate analysis (P = .02). On univariate analysis for toxicity recurrence, Eastern Cooperative Oncology Group performance status and MAX2 score demonstrated an association, with only the latter found to remain statistically significant on multivariate analysis (P = .04). CONCLUSIONS: If a severe toxicity does not have a long duration of impact on ADL, oncologists are less inclined to modify treatment. With proper supportive measures, this leads to recurrence risks similar to those shown in patients with modified treatment, with low risks of toxic deaths overall.