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Background: Malnutrition is common in hospitalized patients with cancer and adversely affects clinical outcomes. We evaluated the prevalence of malnutrition risk, dietitian-identified malnutrition (DIMN), and physician-diagnosed malnutrition (PDMN) at admission., Methods: This retrospective study included adults diagnosed with a stage I-IV solid tumor malignancy and admitted to Atrium Health Carolinas Medical Center from January 2016 to May 2019. Malnutrition risk was determined by a score ≥2 on the Malnutrition Screening Tool (MST) administered by a registered nurse during the intake process. Registered dietitian nutritionist (RDN) assessments were reviewed for DIMN and grade (mild, moderate, or severe). PDMN included malnutrition International Classification of Diseases, Tenth Revision codes in the discharge summary. Univariate models were estimated; multivariate logistic regression models identified associations between clinicodemographic factors and malnutrition prevalence with stepwise selection., Results: A total of 5143 patients were included. Median age was 63 (range 18-102) years, 48% were female, 70% were White, and 24% were Black. Upper gastrointestinal (21%), thoracic (18%), and genitourinary (18%) cancers were most common. A total of 28% had stage IV disease. MST scores were available for 4085 (79%); 1005 of 4085 (25%) were at malnutrition risk. Eleven percent (n = 557) had malnutrition coded by a physician or documented by an RDN; 4% (n = 223) of these were identified by both clinicians, 4% (n = 197) by RDNs only, and 3% (n = 137) by physicians only., Conclusion: Malnutrition appears to be underdiagnosed by both RDNs and physicians. Underdiagnosis of malnutrition may have significant clinical, operational, and financial implications in cancer care., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background: Malnutrition screening is not widely practiced in outpatient cancer centers. This review aims to determine the validity of malnutrition screening tools and provide recommendations for clinical use., Methods: Studies identified by a systematic review assessed the general validity of screening tools in adult oncology outpatients from five databases through 2022. The American Society for Parenteral and Enteral Nutrition (ASPEN) convened a working group of members from the Academy of Nutrition and Dietetics, Academy of Oncology Nurse and Patient Navigators, American Cancer Society, American Society for Clinical Oncology, American Society for Nutrition, American Society for Radiation Oncology, Association of Cancer Care Centers, and Oncology Nursing Society to answer the following questions: (1) should clinicians screen for malnutrition, (2) which malnutrition screening tools are recommended, and (3) what are the clinical applications for malnutrition risk screening in adult oncology outpatients?, Results: Twenty of 738 studies met the criteria and were reviewed. Six screening tools with specific cut-points demonstrated validity and are recommended, including the Mini Nutritional Assessment (≤23.5), Malnutrition Screening Tool (MST; MST ≥ 2 and patient-led MST ≥ 2), Malnutrition Universal Screening Tool (MUST; MUST ≥ 1 and MUST ≥ 2), Nutrition Risk Screening-2002 (NRS-2002; NRS-2002 ≥ 2 and NRS-2002 ≥ 3), NUTRISCORE ≥ 5, and Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF; PG-SGA SF ≥ 7 and PG-SGA SF ≥ 8)., Conclusion: Six screening tools are valid for malnutrition risk identification in oncology ambulatory settings and recommended before treatment initiation and regularly thereafter, depending on treatment course. Research is needed to understand to what extent early diagnosis and management of malnutrition improves the clinical care of oncology patients., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: Fluoropyrimidine-related toxicity and mortality risk increases significantly in patients carrying certain DPYD genetic variants with standard dosing. We implemented DPYD genotyping at a multisite cancer center and evaluated its impact on dosing, toxicity, and hospitalization., Methods: In this prospective observational study, patients receiving (reactive) or planning to receive (pretreatment) fluoropyrimidine-based chemotherapy were genotyped for five DPYD variants as standard practice per provider discretion. The primary end point was the proportion of variant carriers receiving fluoropyrimidine modifications. Secondary end points included mean relative dose intensity, fluoropyrimidine-related grade 3+ toxicities, and hospitalizations. Fisher's exact test compared toxicity and hospitalization rates between pretreatment carriers, reactive carriers, and wild-type patients. Univariable and multivariable logistic regression identified factors associated with toxicity and hospitalization risk. Kaplan-Meier methods estimated time to event of first grade 3+ toxicity and hospitalization., Results: Of the 757 patients who received DPYD genotyping (median age 63, 54% male, 74% White, 19% Black, 88% GI malignancy), 45 (5.9%) were heterozygous carriers. Fluoropyrimidine was modified in 93% of carriers who started treatment. In 442 patients with 3-month follow-up, 64%, 31%, and 30% of reactive carriers, pretreatment carriers, and wild-type patients had grade 3+ toxicity, respectively ( P = .085); 64%, 25%, and 13% were hospitalized ( P < .001). Reactive carriers had 10-fold higher odds of hospitalization compared with wild-type patients ( P = .001), whereas no significant difference was noted between pretreatment carriers and wild-type patients. Time-to-event of toxicity and hospitalization were significantly different between genotype groups ( P < .001), with reactive carriers having the earliest onset and highest incidence., Conclusion: DPYD genotyping prompted fluoropyrimidine modifications in most carriers. Pretreatment testing reduced toxicities and hospitalizations compared with reactive testing, thus normalizing the risk to that of wild-type patients, and should be considered standard practice.

Purpose: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with BRAF alterations treated with regorafenib are reported., Methods: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as investigator assessment of patients with complete or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low accruing histology-specific cohorts with BRAF alterations treated with regorafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, 0.84; α, .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety., Results: Twenty-eight patients with 12 tumor types with BRAF alterations were enrolled from June 2016 to June 2021. All patients were evaluable for efficacy. Two patients with PR and four with SD16+ were observed for DC and OR rates of 21% (90% CI, 12 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected ( P = .24). Eight patients had at least one grade 3 adverse event or serious adverse event at least possibly related to regorafenib., Conclusion: Regorafenib did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with BRAF alterations.

Purpose: To describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired dihydropyrimidine dehydrogenase (DPD) metabolism at a large multisite cancer center, including barriers to implementation and mechanisms to overcome barriers to facilitate test adoption., Summary: Fluoropyrimidines, including fluorouracil and capecitabine, are commonly used chemotherapy agents in the treatment of solid tumors, such as gastrointestinal cancers. DPD is encoded by the DPYD gene, and individuals classified as DPYD intermediate and poor metabolizers due to certain genetic variations in DPYD can experience reduced fluoropyrimidine clearance and an increased risk of fluoropyrimidine-related adverse events. Although pharmacogenomic guidelines provide evidence-based recommendations for DPYD genotype-guided dosing, testing has not been widely adopted in the United States for numerous reasons, including limited education/awareness of clinical utility, lack of testing recommendations by oncology professional organizations, testing cost, lack of accessibility to a comprehensive in-house test and service, and prolonged test turnaround time. Based on stakeholder feedback regarding barriers to testing, we developed an in-house DPYD test and workflow to facilitate testing in multiple clinic locations at Levine Cancer Institute. Across 2 gastrointestinal oncology clinics from March 2020 through June 2022, 137 patients were genotyped, and 13 (9.5%) of those patients were heterozygous for a variant and identified as DPYD intermediate metabolizers., Conclusion: Implementation of DPYD genotyping at a multisite cancer center was feasible due to operationalization of workflows to overcome traditional barriers to testing and engagement from all stakeholders, including physicians, pharmacists, nurses, and laboratory personnel. Future directions to scale and sustain testing in all patients receiving a fluoropyrimidine across all Levine Cancer Institute locations include electronic medical record integration (eg, interruptive alerts), establishment of a billing infrastructure, and further refinement of workflows to improve the rate of pretreatment testing., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Significant progress in our understanding of cancer cachexia has occurred in recent years. Despite these advances, no pharmacologic agent has achieved US Food and Drug Administration approval for this common and highly morbid syndrome. Fortunately, improved understanding of the molecular basis of cancer cachexia has led to novel targeted approaches that are in varying stages of drug development. This article reviews two major thematic areas that are driving these pharmacologic strategies, including those targeting signal mediators at the level of the CNS and skeletal muscle. Additionally, pharmacologic strategies are being tested in combination with targeted nutrients, nutrition therapy, and exercise to treat cancer cachexia. To this end, we highlight recently published and ongoing trials evaluating cancer cachexia therapies in these specific areas.

Purpose: Promising single-agent activity from sotorasib and adagrasib in KRAS G12C -mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS -variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking., Materials and Methods: Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRAS G12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers., Results: Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRAS G12C and 12,126 (88.1%) harboring other KRAS variants ( KRAS non-G12C ). Compared with KRAS non-G12C across all tumor subtypes, KRAS G12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR- P ] = .0006), current or prior smokers (85% v 56%, FDR- P < .0001), and patients age > 60 years (73% v 63%, FDR- P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRAS G12C was most prevalent in patients with non-small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRAS non-G12C -mutated, KRAS G12C -mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR- P < .0001). KRAS G12C -mutated tumors exhibited a distinct comutation profile from KRAS non-G12C -mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR- P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR- P < .01)., Conclusion: This study presents the first large-scale, pan-cancer genomic characterization of KRAS G12C . The KRAS G12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRAS G12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status., Competing Interests: Mohamed E. SalemConsulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol Myers Squibb, Exelixis, QED Therapeutics, Novartis, PfizerSpeakers' Bureau: Taiho Pharmaceutical, Daiichi Sankyo/Astra Zeneca, BMS, Merck Sherif M. El-RefaiEmployment: TempusStock and Other Ownership Interests: Tempus Axel GrotheyHonoraria: Elsevier, Aptitude Health, IMEDEXConsulting or Advisory Role: Genentech/Roche, Bayer (Inst), Bristol Myers Squibb (Inst), Lilly (Inst), Boston Biomedical (Inst), Amgen (Inst), Array BioPharma (Inst), Daiichi Sankyo (Inst), OBI PharmaResearch Funding: Genentech/Roche (Inst), Bayer (Inst), Pfizer (Inst), Eisai (Inst), Lilly (Inst), Boston Biomedical (Inst), Daiichi Sankyo (Inst), Array BioPharma (Inst)Travel, Accommodations, Expenses: Genentech/Roche, Bayer Thomas J. GeorgeConsulting or Advisory Role: Tempus, PfizerResearch Funding: Bristol Myers Squibb (Inst), Merck (Inst), AstraZeneca/MedImmune (Inst), Lilly (Inst), Bayer (Inst), Incyte (Inst), Ipsen (Inst), Seattle Genetics (Inst), Genentech (Inst), Astellas Pharma (Inst), BioMed Valley Discoveries (Inst), GlaxoSmithKline (Inst),Open Payments Link: https://openpaymentsdata.cms.gov/physician/321938 Jimmy J. HwangConsulting or Advisory Role: Bristol Myers Squibb, Boehringer Ingelheim, Caris Centers of Excellence, Pfizer, QED Therapeutics, Deciphera, IncyteSpeakers' Bureau: Bristol Myers Squibb, Deciphera, IncyteResearch Funding: Caris Centers of Excellence (Inst), Boehringer Ingelheim (Inst). Bert O'NeilEmployment: Lilly, TempusHonoraria: AstraZeneca Alexander S. BarrettEmployment: TempusStock and Other Ownership Interests: Tempus Derek RaghavanConsulting or Advisory Role: Gerson Lehrman Group, Caris Life Sciences (Inst). Eric Van CutsemConsulting or Advisory Role: Bayer, Lilly, Roche, SERVIER, Bristol Myers Squibb, Celgene, Merck Sharp & Dohme, Merck KGaA, Novartis, AstraZeneca, Halozyme, Array BioPharma, Biocartis, GlaxoSmithKline, Daiichi Sankyo, Pierre Fabre, Sirtex Medical, Taiho Pharmaceutical, Incyte, Astellas PharmaResearch Funding: amgen (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Lilly (Inst), Novartis (Inst), Roche (Inst), Celgene (Inst), Ipsen (Inst), Merck (Inst), Merck KGaA (Inst), SERVIER (Inst), Bristol Myers Squibb (Inst). Josep TaberneroConsulting or Advisory Role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, Taiho Pharmaceutical, Peptomyc, Chugai Pharma, Pfizer, Seattle Genetics, Array BioPharma, AstraZeneca, Genentech, Menarini, Servier, HalioDx, F. Hoffmann LaRoche, Mirati Therapeutics, Pierre Fabre, Tessa Therapeutics, TheraMyc, Daiichi Sankyo, Samsung Bioepis, IQvia, Ikena Oncology, Merus, Neophore, Orion Biotechnology, Hutchison MediPharma, Avvinity, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna IncOther Relationship: Imedex, Medscape, MJH Life Sciences, Peerview, Physicans' Education Resource Jeanne TieHonoraria: SERVIER, InivataConsulting or Advisory Role: AstraZeneca/MedImmune, Bristol Myers Squibb, Pierre Fabre, MSD Oncology, Inivata, Haystack OncologyNo other potential conflicts of interest were reported.

Background: In cancer, malnutrition is common and negatively impacts tolerance and outcomes of anti-tumor therapies. The aim of this study was to evaluate the prevalence of malnutrition risk and compare the clinicodemographic features between those with high malnutrition screening tool (MST) scores (i.e., ≥ 2 of 5 = high risk for malnutrition, H-MST) to low scores (L-MST)., Methods: A cohort of 3585 patients (May 2017 through December 2018), who completed the MST at least once at the time of diagnosis of any stage solid tumor, were analyzed. Logistic regression tested for associations between clinicodemographic factors, symptom scores, and H-MST prevalence., Results: The median age was 64 years (25-75 IQR, 55-72), with 62% females and 81% White. Most common tumor primary sites were breast (28%), gastrointestinal (GI) (21%), and thoracic (13%). Most had non-metastatic disease (80%). H-MST was found in 28%-most commonly in upper (58%) and lower GI (42%), and thoracic (42%) tumors. L-MST was most common in breast (90%). Multivariable regression confirmed that Black race (OR 1.9, 95% CI 1.5-2.4, p =  < 0.001), cancer primary site (OR 1.6-5.7, p =  < 0.001), stage IV disease (OR 1.8, 95% CI 1.4-2.2, p =  < 0.001), low BMI (OR 4.2, 95% CI 2.5-6.9 p =  < 0.001), and higher symptom scores were all independently associated with H-MST., Conclusions: Twenty-eight percent of solid tumor oncology patients at diagnosis were at high risk of malnutrition. Patients with breast cancer rarely had malnutrition risk at diagnosis. Significant variation was found in malnutrition risk by cancer site, stage, race, and presence of depression, distress, fatigue, and trouble eating/swallowing., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Low socioeconomic status (SES) has been linked to worse survival in patients with colorectal cancer (CRC); however, the impact of SES on early-onset CRC remains undescribed., Materials and Methods: Retrospective analysis of data from the National Cancer Database (NCDB) between 2004 and 2016 was conducted. We combined income and education to form a composite measure of SES. Logistic regression and χ 2 testing were used to examine early-onset CRC according to SES group. Survival rates and Cox proportional hazards models compared stage-specific overall survival (OS) between the SES groups., Results: In total, 30,903 patients with early-onset CRC were identified, of whom 78.7% were White; 14.5% were Black. Low SES compared with high SES patients were more likely to be Black (26.3% vs. 6.1%) or Hispanic (25.3% vs. 10.5%), have T4 tumors (21.3% vs. 17.8%) and/or N2 disease (13% vs. 11.1%), and present with stage IV disease (32.8% vs. 27.7%) at diagnosis (p < .0001, all comparisons). OS gradually improved with increasing SES at all disease stages (p < .001). In stage IV, the 5-year survival rate was 13.9% vs. 21.7% for patients with low compared with high SES. In multivariable analysis, SES (low vs. high group; adjusted hazard ratio [HR adj ], 1.35; 95% confidence interval [CI], 1.26-1.46) was found to have a significant effect on survival (p < .0001) when all of the confounding variables were adjusted. Insurance (not private vs. private; HR adj , 1.38; 95% CI, 1.31-1.44) mediates 31% of the SES effect on survival., Conclusion: Patients with early-onset CRC with low SES had the worst outcomes. Our data suggest that SES should be considered when implementing programs to improve the early detection and treatment of patients with early-onset CRC., Implications for Practice: Low socioeconomic status (SES) has been linked to worse survival in patients with colorectal cancer (CRC); however, the impact of SES on early-onset CRC remains undescribed. In this retrospective study of 30,903 patients with early-onset CRC in the National Cancer Database, a steady increase in the yearly rate of stage IV diagnosis at presentation was observed. The risk of death increased as socioeconomic status decreased. Race and insurance status were independent predictors for survival. Implementation of programs to improve access to care and early diagnostic strategies among younger adults, especially those with low SES, is warranted., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Purpose: Little is known about the use of palliative and hospice care and their impact on healthcare utilization near the end of life (EOL) in early-onset pancreatic cancer (EOPC)., Methods: Patients with EOPC (≤ 50 years) were identified using the institutional tumor registry for years 2011-2018, and demographic, clinical, and rates of referral to palliative and hospice services were obtained retrospectively. Predictors of healthcare utilization, defined as use of ≥ 1 emergency department (ED) visit or hospitalization within 30 days of death, place of death (non-hospital vs. hospital), and time from last chemotherapy administration prior to death, were assessed using descriptive, univariable, and multivariable analyses including chi-square and logistic regression models., Results: A total of 112 patients with EOPC with a median age of 46 years (range, 29-50) were studied. Forty-four percent were female, 28% were Black, and 45% had metastatic disease. Fifty-seven percent received palliative care at a median of 7.8 weeks (range 0-265) following diagnosis. The median time between last chemotherapy and death was 7.9 weeks (range 0-102). Seventy-four percent used hospice services prior to death for a median of 15 days (range 0-241). Rate of healthcare utilization at the EOL was 74% in the overall population. Black race and late use of chemotherapy were independently associated with increase in ED visits/hospitalization and hospital place of death., Conclusions: Although we observed early referrals to palliative care among patients with newly diagnosed EOPC, short duration of hospice enrollment and rates of healthcare utilization prior to death were substantial.

Colon cancer remains a major cause of mortality worldwide. Following adequate surgical resection of lymph node-positive colon cancer, the standard of care since 2004 has been to administer an oxaliplatin-containing regimen (eg, FOLFOX or CAPOX) for 6 months. These regimens have consistently improved oncologic outcomes compared with non-oxaliplatin therapies in multiple adjuvant randomized controlled trials. However, oxaliplatin-induced cumulative dose-dependent neurotoxicity is a major cause of morbidity that can persist years after treatment. The IDEA collaboration is a study that pooled data from 6 concurrent phase 3 trials comparing 3 vs 6 months of adjuvant FOLFOX or CAPOX to evaluate whether a shorter duration of therapy could maintain efficacy while reducing neurotoxicity. In this article, we review the history of adjuvant therapy in stage III colon cancer and comprehensively detail the results of the IDEA collaboration. A risk-based approach focusing on efficacy, toxicity, and patient selection is emphasized to guide discussions regarding the optimal duration of adjuvant therapy in stage III colon cancer.

Purpose: Extending adjuvant endocrine therapy (ET) beyond 5 years has been shown to improve outcomes in breast cancer; however, limited data are available about if and why women pursue extended ET. The primary objective was to estimate the proportion of women who were willing to receive extended ET if recommended by their physician and secondarily, to determine what factors were associated with this decision., Methods: This descriptive cross-sectional study surveyed 131 women with AJCC 7th Edition stages I-III breast cancer who had been taking adjuvant ET for 3-5 years. The survey inquired about the willingness to continue ET, quality of life (FACT-ES), and beliefs about medications (BMQ). Logistic regression was used to test for associations between clinical and disease factors, FACT-ES, BMQ, and the primary outcome., Results: One hundred and twelve (85%) patients reported "moderate" (n = 30, 23%), "quite a bit" (n = 41, 31%), or "extreme" (n = 41, 31%) willingness to pursue extended ET; 19 (14%) patients were "not at all" or were "unlikely" to be willing to take extended ET. On univariate analysis, lower total and social well-being FACT-ES scores, and lower perceived necessity and higher concerns on BMQ were associated with lower willingness to pursue extended ET. On multivariable analysis, greater patient perception of necessity of ET was the only factor associated with willingness to pursue extended ET (OR 1.34, 95% CI 1.15-1.57, p = 0.0005)., Conclusions: Most women who have taken ET for multiple years report being willing to pursue extended ET if recommended. When discussing extended ET, the data from this study support exploring patients' belief of medication necessity.

Purpose: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression., Methods: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured., Results: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover., Conclusions: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI.

Background: Early discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs., Patients and Methods: Postmenopausal women with early-stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24 months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROs on AI discontinuation. Associations between biochemical factors and change in PROs were examined., Results: A total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95% confidence interval (CI), 2.72-2.81; p = .015]; HR, 4.39 [95% CI, 2.40-8.02; p < .0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed., Conclusion: Changes in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation., Implications for Practice: Early changes in patient-reported outcomes (PROs) can predict nonpersistence to aromatase inhibitor therapy. If used in clinical practice, PROs might identify women at highest risk for early discontinuation and allow for interventions to improve tolerance before significant toxicities develop. Further research is needed to improve capturing PROs in routine clinical practice., (©AlphaMed Press.)

Purpose: Hot flashes are a significant source of symptom burden that negatively impacts quality of life (QOL). For women who have contraindications to, or are unwilling to consider, estrogens or antidepressants for bothersome hot flashes, there are limited effective pharmacologic or complementary and alternative medicines., Methods: This single-arm phase II trial studied the efficacy of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Eligible women were required to have reported ≥14 hot flashes per week for ≥1 month. The patients were treated with SAMe at a dose of 400 mg twice daily to evaluate whether a reduction in hot flash score appeared to be better than the historical placebo response of approximately 25%. The women kept a daily hot flash diary during a baseline week and then daily during weeks 2-7. The primary endpoint was the change from baseline to week 7 in hot flash score and hot flash frequency. Secondary endpoints included toxicity analyses and the effect of SAMe on QOL., Results: From October 28, 2010 to January 30, 2012, 43 women were treated with SAMe. The decrease in mean percent of baseline hot flash score and frequency was 35.4 and 32.6%, respectively. When compared to the historical placebo response of 25%, the effect of SAMe on hot flash score was not statistically significant (p = 0.09). Treatment was well tolerated with expected grade 1/2 gastrointestinal toxicity and no negative effect on QOL., Conclusions: The use of SAMe does not appear to significantly reduce hot flashes more than would be expected with a placebo.

Importance: Small cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting., Objective: To molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression., Design, Setting, and Participants: A 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9). After a 6-month response to androgen deprivation therapy, the patient developed jaundice and liver biopsy revealed exclusively NePC. Targeted next generation sequencing (NGS) from formalin-fixed paraffin-embedded (FFPE)-isolated DNA was performed from the diagnostic prostate biopsy and the liver biopsy at progression., Intervention: Androgen deprivation therapy for adenocarcinoma followed by multiagent chemotherapy for NePC., Main Outcomes and Measures: Identification of the mutational landscape in primary adenocarcinoma and NePC liver metastasis. Whether the NePC arose independently or was derived from the primary adenocarcinoma was considered based on mutational profiles., Results: A deleterious somatic SMAD4 L535fs variant was present in both prostate and liver specimens; however, a TP53 R282W mutation was exclusively enriched in the liver specimen. Copy number analysis identified concordant, low-level alterations in both specimens, with focal MYCL amplification and homozygous PTEN, RB1, and MAP2K4 losses identified exclusively in the NePC specimen. Integration with published genomic profiles identified MYCL as a recurrently amplified in NePC., Conclusions and Relevance: NGS of routine biopsy samples from an exceptional non-responder identified SMAD4 as a driver of the aggressive course and supports derivation of NePC from primary adenocarcinoma (transdifferentiation).

Breast cancer remains the leading cause of cancer-related mortality in premenopausal women. Multiple advances in local and systemic therapies have dramatically improved outcomes in women with hormone receptor-positive early-stage breast cancer. Despite these advances, early and late relapses occur. Therefore, multiple adjuvant endocrine therapy trials have been conducted with the goal of decreasing breast cancer recurrence and mortality. Recently, large international trials evaluating extended endocrine therapy and ovarian suppression with and without tamoxifen or exemestane have been reported. These studies add to the large body of existing data on adjuvant endocrine therapy in premenopausal women with breast cancer and provide additional therapeutic options in those at high risk of disease recurrence. This review will synthesize the most recent data and promote an evidence-based approach, highlighting quality-of-life concerns, to considering adjuvant endocrine therapies in premenopausal women.

Background: Despite its clinical utility, progressive reliance on technology can lead to devaluing the physical examination in patients with advanced cancer. The primary objective of this study was to determine whether these patients have a positive or negative perception of the physical examination. A secondary objective was to determine whether these perceptions are related to interpersonal/relational values (symbolic) or diagnostic/objective values (pragmatic)., Methods: One hundred fifty patients with cancer who were receiving concurrent oncology and palliative care were administered a 26-item survey regarding their overall perception of the physical examination. The primary outcome-patient responses to "In the last 3 months, I believe my experience while being examined has been overall: very negative (a score of -5) to very positive (a score of +5),"-was analyzed using the Sign test. Other items were predefined as either symbolic or pragmatic statements, and patient responses from strongly disagree (a score of 1) to strongly agree (a score of 5) were further analyzed. Multivariable logistic regression was used to test for associations between baseline characteristics and the primary outcome., Results: Most patients (83%) indicated that the overall experience of being examined was highly positive (median score, 4; interquartile range [IQR], 2-5; P ≤ .0001). Patients valued both the pragmatic aspects (median score, 5; IQR, 4-5) and symbolic aspects (median score, 4; IQR, 4-5) of the physical examination. Increasing age was independently associated with a more positive perception of the physical examination (odds ratio, 1.07 per year; 95% confidence interval, 1.02-1.12 per year; P = .01)., Conclusions: Patients with advanced cancer indicate that the physical examination is a highly positive aspect of their care. These benefits are perceived as having both symbolic and pragmatic value. The physical examination should remain a cornerstone of clinical encounters., (© 2014 American Cancer Society.)

Context: Conventional chemotherapy leads to multiple adverse mucocutaneous complications such as oral mucositis, alopecia, ocular toxicity, and onycholysis. Limited pharmacologic interventions are available for preventing these clinical problems., Objectives: This study aimed to critically review the role of cryotherapy (regional hypothermia) for alleviating these adverse symptoms., Methods: A narrative review was performed, with an emphasis on randomized controlled trials. A comprehensive search using PubMed, Ovid, Embase, and MEDLINE(®) was completed. References of all cited articles also were reviewed. Data from the review were composed of articles published between 1970 and May 2013., Results: Available evidence suggests that regional hypothermia decreases the burden of chemotherapy-related oral mucositis, alopecia, ocular toxicity, and onycholysis. The major limitations of studies include the absence of blinded control groups and variable clinical end points., Conclusion: Regional hypothermia decreases the burden of these four chemotherapy-induced complications and is well tolerated. More research is needed to determine what subgroups of cancer patients are most likely to respond to different types of regional hypothermia, the ideal duration of cooling needed, and further improve the ease of use of the cooling devices., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy., Methods: A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given., Results: Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE., Conclusions: The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

Purpose: Adherence to guideline-consistent chemotherapy-induced nausea and vomiting (CINV) prophylaxis is suboptimal. The primary aim of this study was to evaluate the magnitude of compliance to institutional guideline-directed antiemetic prophylaxis using a computerized physician order entry system at a single tertiary care institution. A nurse survey was also performed to evaluate how oncology practices, within a cooperative group, managed clinician orders for the prevention of CINV., Methods: The electronic medical records of 100 consecutive patients were evaluated. The primary endpoint was the incidence of compliance to provide all aspects of scheduled institutional guideline-directed antiemetic prophylaxis for acute (day 1) and delayed (days 2-4) CINV. A descriptive analysis was performed on the convenience sample. Logistic regression was completed to determine the predictors of noncompliance., Results: The incidence of compliance on days 1-4 was 94 %. Half of the noncompliant events (three of six, 50 %) occurred on day 1 alone and involved patients receiving low-emetogenic chemotherapy. There was a high degree of compliance to institutional guidelines for the treatment of delayed CINV (97 %). Patients receiving minimally emetogenic and moderately emetogenic chemotherapy (N = 70) were observed to be 100 % compliant. Patients receiving doxorubicin/cyclophosphamide were numerically less likely to receive institutional guidelines, compared to patients receiving other chemotherapy regimens (OR, 0.24 (0.04, 1.36), p value, 0.05). The nurse survey suggested significant variability amongst the involved institutions with regards to antiemetic prescribing practices., Conclusions: Computerized physician order entry is associated with impressive adherence to clinician-prescribing practices, according to institutional guidelines, for acute and delayed CINV.

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease characterized by infiltration of the lung, pleura and mediastinum with thin-walled lymphangiomas. DPL can result in mass effect from infiltrative disease, restrictive and obstructive pulmonary physiology, chylous effusions and respiratory failure. The present article discusses clinical, radiographic and pathological features, and treatment options for DPL.

Background: Chemoprevention with systemic retinoids has demonstrated promise in decreasing the incidence of new primary nonmelanoma skin cancers (NMSCs) in immunocompromised post-transplantation recipients. There is limited evidence for the use of systemic retinoids in the nontransplantation patient. To the authors' knowledge, this is the first randomized controlled trial to assess the efficacy of acitretin as a chemopreventive agent in nontransplantation patients at high-risk for NMSC., Methods: The study was designed as a prospective, randomized, double-blind, placebo-controlled clinical trial. To test the possible skin cancer-preventing effect of a 2-year treatment with acitretin, 70 nontransplantation patients aged ≥18 years who had a history of ≥2 NMSCs within 5 years of trial onset were randomized to receive either placebo or acitretin 25 mg orally 5 days per week. The primary outcome measure was the rate of new NMSC development., Results: Seventy patients were randomized to receive either acitretin alone (N = 35) or placebo (N = 35). During the 2-year treatment period, the patients who received acitretin did not have a statistically significant reduction in the rate of new primary NMSCs (odds ratio, 0.41; 95% confidence interval, 0.15-1.13; 54% vs 74%; P = .13). However, using the incidence of new NMSC, the time to new NMSC, and total NMSC counts, an umbrella test indicated a significant trend that favored the use of acitretin (chi-square statistic, 3.94; P = .047). The patients who received acitretin reported significantly more mucositis and skin toxicities compared with the patients who received placebo., Conclusions: Although there was not a statistically significant benefit observed with the use of acitretin, this may have been the result of low statistical power., (Copyright © 2011 American Cancer Society.)

Patients with advanced cancers often endure chemotherapy late in their disease course leading to unnecessary adverse effects, loss of quality of life, and delay in hospice referral. Compassionate and honest communication about the use of chemotherapy can facilitate better patient care. This manuscript will explore communication issues regarding palliative-intent chemotherapy.