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Mostafa R. Mohamed, Erika Ramsdale, Kah Poh Loh, Huiwen Xu, Amita Patil, Nikesha Gilmore, Spencer Obrecht, Megan Wells, Ginah Nightingale, Katherine M. Juba, Bryan Faller, Adedayo Onitilo, Thomas Bradley, Eva Culakova, Holly Holmes and Supriya G. Mohile

Background: Polypharmacy and potentially inappropriate medications (PIMs) are prevalent in older adults with cancer, but their associations with physical function are not often studied. This study examined the associations of polypharmacy and PIMs with physical function in older adults with cancer, and determined the optimal cutoff value for the number of medications most strongly associated with physical functional impairment. Methods: This cross-sectional analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment. We categorized PIM using 2015 American Geriatrics Society Beers Criteria. Three validated physical function measures were used to assess patient-reported impairments: activities of daily living (ADL) scale, instrumental activities of daily living (IADL) scale, and the Older Americans Resources and Services Physical Health (OARS PH) survey. Optimal cutoff value for number of medications was determined by the Youden index. Separate multivariate logistic regressions were then performed to examine associations of polypharmacy and PIMs with physical function measures. Results: Among 439 patients (mean age, 76.9 years), the Youden index identified ≥8 medications as the optimal cutoff value for polypharmacy; 43% were taking ≥8 medications and 62% were taking ≥1 PIMs. On multivariate analysis, taking ≥8 medications was associated with impairment in ADL (adjusted odds ratio [aOR], 1.64; 95% CI, 1.01–2.58) and OARS PH (aOR, 1.73; 95% CI, 1.01–2.98). PIMs were associated with impairments in IADL (aOR, 1.72; 95% CI, 1.09–2.73) and OARS PH (aOR, 1.97; 95% CI, 1.15–3.37). A cutoff of 5 medications was not associated with any of the physical function measures. Conclusions: Physical function, an important component of outcomes for older adults with cancer, is cross-sectionally associated with polypharmacy (defined as ≥8 medications) and with PIMs. Future studies should evaluate the association of polypharmacy with functional outcomes in this population in a longitudinal fashion.

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Ramy Sedhom, Amanda L. Blackford, Arjun Gupta, Kelly Griffiths, Janet Heussner and Michael A. Carducci

Background: Patients participating in phase I trials represent a population with advanced cancer and symptoms, with quality-of-life implications arising from both disease and treatment. Transitions to end-of-life care for these patients have received little attention. Good empirical data are needed to better understand the role of advance care planning and palliative care during phase I trial transitions. We investigated how physician–patient communication at the time of disease progression, patient characteristics, and patterns of care were associated with end-of-life care. Methods: We conducted a retrospective chart review of all patients with solid tumors enrolled in phase I trials at a comprehensive cancer center from January 2015 to December 2017. We captured physician–patient communication during disease progression. Among patients who died, we assessed palliative care referral, advance care planning, place of death, healthcare use in the final month of life, hospice enrollment, and hospice length of stay (LOS). Factors independently associated with a short hospice LOS (defined as ≤3 days) were estimated from a multivariable model building approach. Results: Among 207 participants enrolled in phase I intervention studies at Johns Hopkins Hospital, the median age was 61 years (range, 31–91 years), 48% were women, 21% were members of racial minority groups, and 41.5% were referred from an outside institution. At the time of disease progression, 53% had goals of care documented, 47% were previously referred to palliative care, and 41% discussed hospice with their oncologist. A total of 82% of decedents died within 1 year of study enrollment, and 85% enrolled in hospice. Among the 147 participants who enrolled in hospice, 22 (15%) had a short LOS (≤3 days). Factors independently associated with an increased risk of short hospice LOS in the multivariable model included age >65 years (odds ratio [OR], 1.12; 95% CI, 1.01–1.24; P=.04), whereas remaining at the same institution (OR, 0.72; 95% CI, 0.65–0.80; P<.001) and referral to palliative care before progression (OR, 0.83; 95% CI, 0.75–0.92; P<.001) were associated with a decreased risk of short hospice LOS. Conclusions: Reported data support the benefit of palliative care for patients in phase I trials and the risks associated with healthcare transitions for all patients, particularly older adults, regardless of care received. Leaving a clinical trial is a time when clear communication is paramount. Phase I studies will continue to be vital in advancing cancer treatment. It is equally important to advance the support provided to patients who transition off these trials.

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Willemieke P.M. Dijksterhuis, Anouk E.J. Latenstein, Jessy Joy van Kleef, Rob H.A. Verhoeven, Jeanne H.M. de Vries, Marije Slingerland, Elles Steenhagen, Joos Heisterkamp, Liesbeth M. Timmermans, Marian A.E. de van der Schueren, Martijn G.H. van Oijen, Sandra Beijer and Hanneke W.M. van Laarhoven

Background: Cachexia is common in patients with esophagogastric cancer and is associated with increased mortality. Nutritional screening and dietetic interventions can be helpful in preventing evolvement of cachexia. Our aim was to study the real-world prevalence and prognostic value of pretreatment cachexia on overall survival (OS) using patient-reported weight loss, and to explore dietetic interventions in esophagogastric cancer. Materials and Methods: Patients with esophagogastric cancer (2015–2018), regardless of disease stage, who participated in the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) and completed patient-reported outcome measures were included. Data on weight loss and dietetic interventions were retrieved from questionnaires before start of treatment (baseline) and 3 months thereafter. Additional patient data were obtained from the Netherlands Cancer Registry. Cachexia was defined as self-reported >5% half-year body weight loss at baseline or >2% in patients with a body mass index (BMI) <20 kg/m2 according to the Fearon criteria. The association between cachexia and OS was analyzed using multivariable Cox proportional hazard analyses adjusted for sex, age, performance status, comorbidities, primary tumor location, disease stage, histology, and treatment strategy. Results: Of 406 included patients, 48% had pretreatment cachexia, of whom 65% were referred for dietetic consultation at baseline. The proportion of patients with cachexia was the highest among those who received palliative chemotherapy (59%) or best supportive care (67%). Cachexia was associated with decreased OS (hazard ratio, 1.52; 95% CI, 1.11–2.09). Median weight loss after 3-month follow-up was lower in patients with cachexia who were referred to a dietician at baseline compared with those who were not (0% vs 2%; P=.047). Conclusions: Nearly half of patients with esophagogastric cancer have pretreatment cachexia. Dietetic consultation at baseline was not reported in more than one-third of the patients with cachexia. Because cachexia was independently associated with decreased survival, improving nutritional screening and referral for dietetic consultation are warranted to prevent further deterioration of malnutrition and mortality.

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Fei Gao, Nan Li, YongMei Xu and GuoWang Yang

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Gabrielle Gauvin, Chi Chi Do-Nguyen, Johanna Lou, Eileen Anne O’Halloran, Leigh T. Selesner, Elizabeth Handorf, Molly E. Collins and Jeffrey M. Farma

Background: Gastrostomy tubes (G-tubes) are invaluable clinical tools that play a role in palliation and nutrition in patients with cancer. This study aimed to better understand the risks and benefits associated with the placement and maintenance of G-tubes. Methods: Patients who underwent placement of a G-tube for cancer from January 2013 through December 2017 at a tertiary care center were considered for inclusion. Clinical data were retrospectively collected from medical records. Results: A total of 242 patients with cancer, whose average age at diagnosis was 61 years (range, 21–94 years), underwent G-tube placement for nutrition (76.4%), decompression (22.7%), or both (0.8%). Successful insertion was achieved in 96.8%, but 8 patients required >1 attempted method of insertion. In the decompression group, minor postplacement complications were less common (23.6% vs 53.5%; P<.001) and survival was shorter (P<.001) compared with the nutrition group. For those with decompressive G-tubes, 45.5% had a palliative care consult; 56.4% were seen by social workers; and 46.3% went to hospice. The frequency of hospice discharge was higher in patients who had consults (53.7% vs 23.1%; P=.01). Conclusions: Half of the patients who received decompressive G-tubes presented with stage IV disease and died within 1 month of placement. Those with >1 consult were more likely to be discharged to hospice. Patients with G-tubes for nutrition saw no change in functionality, complication rate, or survival, regardless of adjunct chemotherapy status. These findings illustrate the need for a tool to allow a better multidisciplinary approach and interventional decision-making for patients with cancer.

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Mary B. Daly, Tuya Pal, Michael P. Berry, Saundra S. Buys, Patricia Dickson, Susan M. Domchek, Ahmed Elkhanany, Susan Friedman, Michael Goggins, Mollie L. Hutton, CGC, Beth Y. Karlan, Seema Khan, Catherine Klein, Wendy Kohlmann, CGC, Allison W. Kurian, Christine Laronga, Jennifer K. Litton, Julie S. Mak, LCGC, Carolyn S. Menendez, Sofia D. Merajver, Barbara S. Norquist, Kenneth Offit, Holly J. Pederson, Gwen Reiser, CGC, Leigha Senter-Jamieson, CGC, Kristen Mahoney Shannon, Rebecca Shatsky, Kala Visvanathan, Jeffrey N. Weitzel, Myra J. Wick, Kari B. Wisinski, Matthew B. Yurgelun, Susan D. Darlow and Mary A. Dwyer

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.

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Robert Pilarski

Historically, genetic testing (and billing) for hereditary cancer risk was essentially performed gene by gene, with clinicians ordering testing only for the genes most likely to explain a patient’s or family’s cancer presentation, with laboratories typically charging $1,000 to $1,500 for each gene that was sequenced. Given the expense, only patients at high risk of having a hereditary syndrome were offered testing. With the introduction of next-generation sequencing technologies, however, laboratories are able to test for multiple genes at the same time with greater efficiency, significantly decreased costs, and relatively little increased expense when adding additional genes. This has drastically altered clinical practice so that clinicians now typically order testing for a panel of multiple genes for most patients. Although this approach has streamlined the diagnostic odyssey, it has introduced several problems, as well, including difficulties in choosing the appropriate panel test for a given patient, assessing the significance of identified genetic variants (including variants of uncertain significance [VUS]), and understanding the disease risks and management associated with pathogenic variants in a given gene. Many laboratories offer testing for genes that have limited data supporting their associated cancer risks, which then leads to an inability to set management guidelines based on that gene. In addition, testing larger numbers of genes increases the likelihood of finding one or more VUS, which introduce their own management issues. Thus, although panel testing has certainly moved clinical practice forward in many ways, it has also raised its own set of problems that increase the complexity of genetic counseling and highlight the need for education of community practitioners on the complexities and nuances of this testing. Whenever possible, testing should be performed by, or in consultation with, cancer genetics professionals.