Patients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in nine patients (35%). In the remaining 17, 90.3% (95% CI: 73.1–97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r=0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful.
The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4 ؉ T cells >400 per l. CD4 ؉ T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-␥-producing HIV-1-specific CD8 ؉ and CD4 ؉ T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8 ؉ T cell responses in all eight STI subjects (P ؍ 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4 ؉ T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P ؍ 0.001 and 0.34, respectively). CD4 ؉ T cell counts were regained on return to HAART. Control subjects (n ؍ 4) maintained VL <400 copies per ml and stable CD4 ؉ T cell counts, and showed no enhancement of antiviral CD8 ؉ T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.
The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.
Context. No information is available on oncology patients' level of stress and symptom burden during the coronavirus disease 2019 (COVID-19) pandemic. Objectives. To evaluate for differences in demographic and clinical characteristics, levels of social isolation and loneliness, and the occurrence and severity of common symptoms between oncology patients with low vs. high levels of COVID-19 and cancer-related stress. In addition, to determine which of these characteristics were associated with membership in the highstressed group. Methods. Patients were 18 years and older; had a diagnosis of cancer; and were able to complete an online survey. Results. Of the 187 patients in this study, 31.6% were categorized in the stressed group (Impact of Event ScaledRevised [score of $24]). Stressed group's Impact of Event ScaledRevised score exceeds previous benchmarks in oncology patients and equates with probable post-traumatic stress disorder. In this stressed group, patients reported occurrence rates for depression (71.2%), anxiety (78.0%), sleep disturbance (78.0%), evening fatigue (55.9%), cognitive impairment (91.5%), and pain (75.9%). Symptom severity scores equate with clinically meaningful levels for each symptom. Conclusion. We identified alarmingly high rates of stress and an extraordinarily high symptom burden among patients with cancer, exceeding those previously benchmarked in this population and on par with noncancer patients with post-traumatic stress disorder. Given that the COVID-19 pandemic will likely impact cancer care for an indefinite period, clinicians must exhibit increased vigilance in their assessments of patients' level of stress and symptom burden. Moreover, an increase in referrals to appropriate supportive care resources must be prioritized for high-risk patients. J Pain Symptom Manage 2020;60:e25ee34.
Neuroendocrine tumors (NETs) metastasize to bone; however, a multi-institution evaluation of the natural history and complications of bone metastases across multiple NET subtypes has not, to our knowledge, previously been conducted. At two tertiary academic centers, we identified patients with bone metastases from databases of patients with a diagnosis of NET between 2004 and 2008. Detection of bone metastases, occurrence of skeletal-related events (SREs), and interventions were analyzed using summary statistics and categorical methods. Time-to-event data were assessed using Kaplan–Meier estimates and log-rank tests. Between 2004 and 2008, 82 out of 691 NET patients (12%) were reported to have bone metastases. Of the 82 patients with bone metastases, 55% were men and their median age was 49. Bone metastases occurred in 25% of pheochromocytomas and paragangliomas, 20% of high-grade neuroendocrine carcinomas, 9% of carcinoid tumors, and 8% of pancreatic NETs. At time of detection of bone metastases, 60% reported symptoms, including pain; 10% developed cord compression, 9% suffered a pathological fracture, and 4% developed hypercalcemia. Occurrence of SREs did not differ significantly with regard to tumor histology. Of patients with bone metastases, 67 (82%) received at least one form of bone-directed treatment, 50% received radiation, 45% received a bisphosphonate, 18% underwent surgery, 11% received 131I-MIBG, 5% received denosumab, and 46% were treated with more than one treatment modality. Bone metastases occur in a substantial number of patients diagnosed with NETs. Patients are often symptomatic and many develop SREs. Given the recent therapeutic advances and increasing life expectancy of patients with NETs, development of guidelines for surveillance and clinical care of bone metastases from NETs is needed.
BackgroundOver 1.3 million people live with colorectal cancer in the United States. Physical activity is associated with lower risk of colorectal cancer recurrence and mortality. Interventions are needed to increase physical activity in colorectal cancer survivors.MethodsWe conducted a 2-arm non-blinded pilot randomized controlled trial at the University of California, San Francisco among 42 individuals who had completed curative-intent treatment for colorectal cancer to determine the feasibility and acceptability of a 12-week (84 days) physical activity intervention using a Fitbit Flex™ and daily text messages. Participants were randomized 1:1 to receive the intervention with print educational materials or print educational materials alone. We explored the impact of the intervention versus usual care on physical activity using ActiGraph GT3X+ accelerometers pre−/post-intervention.ResultsWe screened 406 individuals and randomized 42 to intervention (n = 21) or control (n = 21) groups. During the 12-week study, the intervention arm wore their Fitbits a median of 74 days [88% of days in study period, interquartile range: 23–83 days] and responded to a median of 34 (out of 46) text messages that asked for a reply (interquartile range: 13–38 text messages). Among the 16 intervention participants who completed the feedback survey, the majority (88%) reported that the intervention motivated them to exercise and that they were satisfied with their experience. No statistically significant difference in change in moderate-to-vigorous physical activity was found from baseline to 12 weeks between arms.ConclusionA 12-week physical activity intervention with a Fitbit and text messages was feasible and acceptable among colorectal cancer patients after curative treatment. Larger studies are needed to determine whether the intervention increases physical activity.Trial registrationClinicaltrials.gov Identifier NCT02966054. Registered 17 November 2016, retrospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5427-5) contains supplementary material, which is available to authorized users.
Cancer during pregnancy is relatively rare but is increasing in frequency in countries in which the maternal child-bearing age continues to rise. The complexities of medical decision making are underscored by the need to weigh the potential benefits of any intervention for the mother against the risks to the fetus. A majority of diagnostic evaluations can be performed safely in the setting of pregnancy and should not be delayed. Noninvasive prenatal testing that shows discordance with fetal karyotype can be a clue to an underlying maternal malignancy. After diagnosis, a multidisciplinary team should formulate a care plan for both the mother and the fetus. Key topics for discussion should include the mother’s prognosis, standard treatment plan, and predictions of how modifications for a continuing pregnancy will affect the treatment plan and overall prognosis. In the context of this knowledge, frank discussions about pregnancy termination should be addressed with the patient, if appropriate. Selection of a plan for oncologic management in the case of a pregnant woman is based on the type of cancer, the tumor biology, and the tumor stage. Additional complexities for pregnant patients are typically related to the gestational age of the fetus, the dynamic physiologic changes of pregnancy, and the limited safety data for administration of most anticancer therapies during pregnancy. In this article, we summarize data related to different classes of anticancer therapies as well as considerations for the management of selected cancers. Finally, we provide some key principles that should be considered in the management of patients with cancer during pregnancy.
clinicaltrials.gov Identifier: NCT02217865.
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