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Henry M Smilowitz,1 Alexandria Meyers,1 Khalil Rahman,1 Nathaniel A Dyment,2 Dan Sasso,1 Crystal Xue,3 Douglas L Oliver,4 Alexander Lichtler,5 Xiaomeng Deng,6 Sharif M Ridwan,1 Lauren J Tarmu,7,8 Qian Wu,9 Andrew L Salner,10 Ketan R Bulsara,11 Daniel N Slatkin,12 James F Hainfeld12 1Department of Cell Biology, University of Connecticut Health Center, Farmington, CT, 2Department of Orthopedic Surgery, University of Pennsylvania, Philadelphia, PA, 3George Washington University School of Medicine, Washington, DC, 4Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, 5Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, 6David Geffen School of Medicine at UCLA, Student Affairs Office, Los Angeles, CA, 7Department of Human Behavior, College of Southern Nevada, 8Department of Anthropology, University of Nevada, Las Vegas, NV, 9Department of Anatomic Pathology, University of Connecticut Health Center, Farmington, 10The Gray Cancer Center, Hartford Hospital, Hartford, 11Division of Neurosurgery, UConn Health, Farmington, CT, 12Nanoprobes, Inc, Yaphank, NY, USA Background: Intravenously (IV)-injected gold nanoparticles (AuNPs) powerfully enhance the efficacy of X-ray therapy of tumors including advanced gliomas. However, pharmacokinetic issues, such as slow tissue clearance and skin discoloration, may impede clinical translation. The direct infusion of AuNPs into the tumor might be an alternative mode of delivery. Materials and methods: Using the advanced, invasive, and difficult-to-treat F98 rat glioma model, we have studied the biodistribution of the AuNPs in the tumor and surrounding brain after either IV injection or direct intratumoral infusion by convection-enhanced delivery using light microscopy immunofluorescence and direct gold visualization. Results: IV-injected AuNPs localize more specifically to intracerebral tumor cells, both in the main tumor mass and in the migrated tumor cells as well as the tumor edema, than do the directly infused AuNPs. Although some of the directly infused AuNPs do access the main tumor region, such access is largely restricted. Conclusion: These data suggest that IV-injected AuNPs are likely to have a greater therapeutic benefit when combined with radiation therapy than after the direct infusion of AuNPs. Keywords: gold nanoparticles, glioma, edema, IV injection, convection-enhanced delivery, fluorescence microscopy, gold enhance

Background: Worse survival persists for African-Americans (AA) with breast cancer compared to other race/ethnic groups despite recent improvements for all. Unstudied in outcomes disparities to date is soluble LAG-3 (sLAG-3), cleaved from the LAG-3 immune checkpoint receptor which is a proposed target for deactivation in emerging immunotherapies due to its prominent immunosuppressive function in the tumoral microenvironment. A prior study has found that lower sLAG-3 baseline level was associated with poor outcomes., Methods: In a cross-sectional study of 95 patients with primary breast cancer (n = 58 Caucasian, n = 37 AA), we measured sLAG-3 (ELISA pg/ml) in pre-treatment blood samples using the non-parametric Mann-Whitney u-Test for independent samples, and, calculated Pearson r correlation coefficients of sLAG-3 with circulating cytokines by race., Results: Mean sLAG-3 level was lower in AA compared to Caucasian patients (1377.6 vs 3690.3, P = .002), and in patients with triple-negative breast cancer (TNBC) compared to those with non-TNBC malignancies (P = .02). When patients with TNBC tumors were excluded from analyses, the difference in sLAG-3 level between AA (n = 21) and Caucasian patients (n = 40) substantially remained (1937.4 vs 4182.4, P = .06). Among Caucasian patients, sLAG-3 was correlated with IL-6, IL-8 and IL-10 (r = .69, P < .001; r = .70, P < .001; and, r = .46, P = .01; respectively). For AA patients, sLAG-3 was correlated only with IL-6 (r = .37, P = .03)., Conclusions: We present the first report that African-American breast cancer patients might have comparatively low pre-treatment sLAG-3 levels, independent of TNBC status, along with reduced co-expression with circulating cytokines. The mechanistic and prognostic role of cleaved LAG-3, particularly in disparate outcomes, remains to be elucidated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To describe longitudinal oral health symptom patterns of patients receiving concurrent chemotherapy and radiation therapy for head and neck cancer (HNC) and examine associations between phenotypic characteristics, including human papillomavirus (HPV) status and oral health symptoms., Sample & Setting: A pilot retrospective longitudinal chart review (N = 270) of patients with HNC at a northeastern U.S. regional cancer institute., Methods & Variables: HPV status and oral health symptoms (pain, mucositis, taste alteration, xerostomia, dysphagia, and candidiasis) were examined during treatment (six weeks) and survivorship (three months). Latent transition analysis was conducted across each time point., Results: The latent transition analysis revealed classes with moderate to high symptom expression persisted into survivorship. The HPV-negative phenotype had higher symptom expression across treatment and survivorship., Implications for Nursing: Patients with HPV-negative HNC may require early intervention, while considering social determinants of health to attenuate symptom expression and improve outcomes.

Importance: For patients with nonspine bone metastases, short-course radiotherapy (RT) can reduce patient burden without sacrificing clinical benefit. However, there is great variation in uptake of short-course RT across practice settings., Objective: To evaluate whether a set of 3 implementation strategies facilitates increased adoption of a consensus recommendation to treat nonspine bone metastases with short-course RT (ie, ≤5 fractions)., Design, Setting, and Participants: This prospective, stepped-wedge, cluster randomized quality improvement study was conducted at 3 community-based cancer centers within an existing academic-community partnership. Rollout was initiated in 3-month increments between October 2021 and May 2022. Participants included treating physicians and patients receiving RT for nonspine bone metastases. Data analysis was performed from October 2022 to May 2023., Exposures: Three implementation strategies-(1) dissemination of published consensus guidelines, (2) personalized audit-and-feedback reports, and (3) an email-based electronic consultation platform (eConsult)-were rolled out to physicians., Main Outcomes and Measures: The primary outcome was adherence to the consensus recommendation of short-course RT for nonspine bone metastases. Mixed-effects logistic regression at the bone metastasis level was used to model associations between the exposure of physicians to the set of strategies (preimplementation vs postimplementation) and short-course RT, while accounting for patient and physician characteristics and calendar time, with a random effect for physician. Physician surveys were administered before implementation and after implementation to assess feasibility, acceptability, and appropriateness of each strategy., Results: Forty-five physicians treated 714 patients (median [IQR] age at treatment start, 67 [59-75] years; 343 women [48%]) with 838 unique nonspine bone metastases during the study period. Implementing the set of strategies was not associated with use of short-course RT (odds ratio, 0.78; 95% CI, 0.45-1.34; P = .40), with unadjusted adherence rates of 53% (444 lesions) preimplementation vs 56% (469 lesions) postimplementation; however, the adjusted odds of adherence increased with calendar time (odds ratio, 1.68; 95% CI, 1.20-2.36; P = .003). All 3 implementation strategies were perceived as being feasible, acceptable, and appropriate; only the perception of audit-and-feedback appropriateness changed before vs after implementation (19 of 29 physicians [66%] vs 27 of 30 physicians [90%]; P = .03, Fisher exact test), with 20 physicians (67%) preferring reports quarterly., Conclusions and Relevance: In this quality improvement study, a multicomponent set of implementation strategies was not associated with increased use of short-course RT within an academic-community partnership. However, practice improved with time, perhaps owing to secular trends or physician awareness of the study. Audit-and-feedback was more appropriate than anticipated. Findings support the need to investigate optimal approaches for promoting evidence-based radiation practice across settings.

Purpose: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites., Methods: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center., Results: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively., Conclusion: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment., Competing Interests: Daniel R. GomezHonoraria: Varian Medical Systems, Merck, Bristol Myers Squibb, AstraZeneca, RefleXion Medical, Vindico Medical Education, US Oncology, GRAILConsulting or Advisory Role: Olympus Medical Systems, Medtronic, Johnson & Johnson/JanssenResearch Funding: Merck, Varian Medical Systems, AstraZeneca, Bristol Myers SquibbTravel, Accommodations, Expenses: Varian Medical Systems, AstraZeneca, Merck, Vindico Medical Education, US Oncology, Driver Inc Jonathan T. YangStock and Other Ownership Interests: Nanocan TherapeuticsConsulting or Advisory Role: Debiopharm Group, Galera Therapeutics, AstraZeneca, Nanocan TherapeuticsResearch Funding: AstraZeneca, Kazia Therapeutics, X-RAD Therapeutics Nancy Y. LeeConsulting or Advisory Role: Merck, Pfizer, Merck Serono, Sanofi, Mirati Therapeutics, Roche/GenentechResearch Funding: AstraZeneca, Pfizer (Inst) Andreas RimnerHonoraria: More HealthConsulting or Advisory Role: AstraZeneca, Merck, Boehringer IngelheimResearch Funding: Varian Medical Systems (Inst), Boehringer Ingelheim (Inst), Pfizer (Inst), AstraZeneca (Inst), Merck (Inst) Yoshiya YamadaEmployment: Memorial Sloan-Kettering Cancer CenterLeadership: Chordoma FoundationHonoraria: Varian Medical Systems, BrainLAB, Vision RTSpeakers' Bureau: BrainLAB, Vision RT, Varian Medical SystemsResearch Funding: Varian Medical SystemsTravel, Accommodations, Expenses: Philips HealthcareOther Relationship: University of Wollongong Michael J. ZelefskyHonoraria: AccurayConsulting or Advisory Role: Alpha Tau, Boston ScientificPatents, Royalties, Other Intellectual Property: Ferring provided partial funding for a clinical trial (Inst)Other Relationship: Editor in Chief for Brachytherapy Noah S. KalmanConsulting or Advisory Role: Naveris Rupesh R. KotechaHonoraria: Accuray, Novocure, Elekta, BrainLAB, Elsevier, ViewRay, PeerViewConsulting or Advisory Role: ViewRay, NovocureSpeakers' Bureau: NovocureResearch Funding: Medtronic (Inst), Blue Earth Diagnostics (Inst), Novocure (Inst), GT Medical Technologies (Inst), AstraZeneca (Inst), Exelixis (Inst), ViewRay (Inst), BrainLAB (Inst)Travel, Accommodations, Expenses: PeerView Minesh P. MehtaLeadership: OncoceuticsStock and Other Ownership Interests: ChimerixConsulting or Advisory Role: Karyopharm Therapeutics, Mevion Medical Systems, ZappRx, Sapience Therapeutics, XoftPatents, Royalties, Other Intellectual Property: WARF patent 14/934,27, Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapyUncompensated Relationships: Xcision Medical Systems, ViewRay Michael D. ChuongEmployment: Fertility and IVF Center of MiamiHonoraria: ViewRay, Sirtex MedicalConsulting or Advisory Role: ViewRay, Advanced Accelerator ApplicationsSpeakers' Bureau: ViewRay, Sirtex MedicalResearch Funding: AstraZeneca/MedImmune, ViewRayTravel, Accommodations, Expenses: ViewRay Andrew L. SalnerConsulting or Advisory Role: Best Doctors Inc Jamie S. OstroffPatents, Royalties, Other Intellectual Property: UptoDate David G. PfisterConsulting or Advisory Role: Boehringer Ingelheim, IncyteResearch Funding: Boehringer Ingelheim (Inst), AstraZeneca (Inst), Exelixis (Inst), Novartis (Inst), MedImmune (Inst), Merck (Inst), Genentech/Roche (Inst), Lilly (Inst), Bayer (Inst), Eisai (Inst), Regeneron (Inst), Atara Biotherapeutics (Inst), MeiraGTx (Inst), Hookipa Pharma (Inst) Fumiko ChinoThis author is a Consultant Editor for JCO Oncology Practice. Journal policy recused the author from having any role in the peer review of this manuscript. Jillian TsaiHonoraria: Varian Medical IncConsulting or Advisory Role: Varian Medical Systems Erin F. GillespieOther Relationship: eContourNo other potential conflicts of interest were reported.

Purpose: Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership., Methods and Materials: A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement., Results: Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3)., Conclusions: Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: To characterize the needs and preferences for pain self-management support (SMS) among patients with cancer during the transition of cancer care from the hospital to the home setting., Sample & Setting: 38 participants with cancer pain at a research-intensive cancer center in New England., Methods & Variables: A descriptive, cross-sectional survey study was conducted to investigate relationships among preferred and received support, extent and management of transitional change, and pain outcomes. Pain intensity and interference were measured using the Brief Pain Inventory-Short Form, transitional change was measured using the Measurement of Transitions in Cancer Scale, and SMS was measured using dichotomous questions., Results: About half of participants reported concordance between preferred and received cancer pain SMS in the hospital and at home. The extent of transitional change in cancer care was found to be a significant predictor of average pain intensity in the hospital and pain interference at home. Satisfaction with cancer pain SMS was a significant predictor of pain intensity at home., Implications for Nursing: The extent of change during care transitions should be considered when fulfilling patient needs and preferences for cancer pain SMS to optimize outcomes.

Purpose: A substantial portion of breast cancer survivors are active in the workforce, yet factors that allow survivors to balance work with cancer management and to return to work are poorly understood. We examined breast cancer survivors' most valued/desired types of support in early survivorship., Methods: Seventy-six employed breast cancer survivors answered an open-ended survey question assessing the most valued/desired support to receive from healthcare providers during early survivorship to manage work and health. Cutrona's (Journal of Social and Clinical Psychology 9:3-14, 1990) optimal matching theory and House's (1981) conceptualization of social support types informed our analyses. Data were content-analyzed to identify themes related to support, whether needed support was received or not, and the types of healthcare providers who provided support., Results: We identified six themes related to types of support. Informational support was valued and mostly received by survivors, but they expected more guidance related to work. Emotional support was valued but lacking, attributed mainly to providers' lack of personal connection and mental health support. Instrumental (practical) support was valued but received by a small number of participants. Quality of life support to promote well-being and functionality was valued and often received. Other themes included non-specific support and non-support., Conclusions: This study expands our understanding of how breast cancer survivors perceive work-related support from healthcare professionals. Findings will inform targeted interventions designed to improve the support provided by healthcare professionals., Implications for Cancer Survivors: Breast cancer survivors managing work and health challenges may benefit by having their unmet support needs fulfilled., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Survivors of head and neck cancer (HNC) can have multiple health concerns. To facilitate their care, we developed and pilot-tested a clinical informatics intervention, HN-STAR. HN-STAR elicits concerns online from HNC survivors prior to a routine oncology clinic visit. HN-STAR then presents tailored evidence-based clinical recommendations as a clinical decision support tool to be used during the visit where the oncology clinician and survivor select symptom management strategies and other actions. This generates a survivorship care plan (SCP). Online elicitation of health concerns occurs 3, 6, and 9 months after the clinic visit, generating an updated SCP each time. HN-STAR encompasses important methods of improving survivorship care (e.g., needs assessment, tailored interventions, dissemination of guidelines) and will be evaluated in a pragmatic trial to maximize external validity. This hybrid type 1 implementation-effectiveness trial tests HN-STAR effectiveness while studying barriers and facilitators to implementation in community oncology practices within the National Cancer Institute Community Oncology Research Program. Effectiveness will be measured as differences in key survivorship outcomes between HNC participants who do and do not use HN-STAR over one year after the clinic visit. The primary endpoint is HNC-specific quality of life; other outcomes include patient-centered measures and receipt of guideline-concordant care. Implementation outcomes will be assessed of survivors, providers, and clinic stakeholders. The hybrid design will provide insight into a dose-response relationship between the extent of implementation fidelity and effectiveness outcomes, as well as how to incorporate HN-STAR into standard practice outside the research setting., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Lutetium Lu-177 dotatate is the first peptide receptor radionuclide therapy approved by the US Food and Drug Administration. Well-designed studies in Europe have shown dramatic effectiveness in improving progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, which are progressive and generally metastatic. This therapy is a molecular targeted therapy linking a beta-emitting radioisotope to dotatate, which binds tightly to somatostatin receptors on neuroendocrine tumors cells. Various adverse effects of this therapy have been reported in the literature, including potential toxicity to renal, hepatic, and hematologic tissues and risk of second malignancy. Our study sought to explore acute adverse effects in this patient population., Methods and Materials: We tracked adverse effects and patient experience in our first year of therapy experience with this new agent., Results: In our first 12 patients who received Lutetium Lu-177 dotatate, tumor flare reactions occurred in 5 patients due to worsening symptoms of bone or soft tissue metastasis. This flare reaction can be mitigated with short course of corticosteroid therapy or other strategies., Conclusions: Flare reaction is common in patients with progressive metastatic gastroenteropancreatic neuroendocrine tumors and can be managed successfully with several strategies., (© 2020 The Author(s).)

A broad range of fungi has been detected in molecular surveys of the oral mycobiome. However, knowledge is still lacking on interindividual variability of these communities and the ecologic and clinical significance of oral fungal commensals. In this cross-sectional study, we use internal transcribed spacer 1 amplicon sequencing to evaluate the salivary mycobiome in 59 subjects, 36 of whom were scheduled to receive cancer chemotherapy. Analysis of the broad population structure of fungal communities in the whole cohort identified 2 well-demarcated genus-level community types (mycotypes), with Candida and Malassezia as the main taxa driving cluster partitioning. The Candida mycotype had lower diversity than the Malassezia mycotype and was positively correlated with cancer and steroid use in these subjects, smoking, caries, utilizing a removable prosthesis, and plaque index. Mycotypes were also associated with metabolically distinct bacteria indicative of divergent oral environments, with aciduric species enriched in the Candida mycotype and inflammophilic bacteria increased in the Malassezia mycotype. Similar to their fungal counterparts, coexisting bacterial communities associated with the Candida mycotype showed lower diversity than those associated with the Malassezia mycotype, suggesting that common environmental pressures affected bacteria and fungi. Mycotypes were also seen in an independent cohort of 24 subjects, in which cultivation revealed Malassezia as viable oral mycobiome members, although the low-abundance Malassezia sympodialis was the only Malassezia species recovered. There was a high degree of concordance between the molecular detection and cultivability of Candida , while cultivation showed low sensitivity for detection of the Malassezia mycotype. Overall, our work provides insights into the oral mycobiome landscape, revealing 2 community classes with apparently distinct ecologic constraints and specific associations with coexisting bacteria and clinical parameters. The utility of mycotypes as biomarkers for oral diseases warrants further study.

Oral candidiasis is a common side effect of cancer chemotherapy. To better understand predisposing factors, we followed forty-five subjects who received 5-fluorouracil- or doxorubicin-based treatment, during one chemotherapy cycle. Subjects were evaluated at baseline, prior to the first infusion, and at three additional visits within a two-week window. We assessed the demographic, medical and oral health parameters, neutrophil surveillance, and characterized the salivary bacteriome and mycobiome communities through amplicon high throughput sequencing. Twenty percent of all subjects developed oral candidiasis. Using multivariate statistics, we identified smoking, amount of dental plaque, low bacteriome and mycobiome alpha-diversity, and the proportions of specific bacterial and fungal taxa as baseline predictors of oral candidiasis development during the treatment cycle. All subjects who developed oral candidiasis had baseline microbiome communities dominated by Candida and enriched in aciduric bacteria. Longitudinally, oral candidiasis was associated with a decrease in salivary flow prior to lesion development, and occurred simultaneously or before oral mucositis. Candidiasis was also longitudinally associated with a decrease in peripheral neutrophils but increased the neutrophil killing capacity of Candida albicans . Oral candidiasis was not found to be associated with mycobiome structure shifts during the cycle but was the result of an increase in Candida load, with C. albicans and Candida dubliniensis being the most abundant species comprising the salivary mycobiome of the affected subjects. In conclusion, we identified a set of clinical and microbiome baseline factors associated with susceptibility to oral candidiasis, which might be useful tools in identifying at risk individuals, prior to chemotherapy.

Background: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues., Results: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity., Conclusions: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.

African-American (AA) cancer patients have long-experienced worse outcomes compared to non-Hispanic whites (NHW). No studies to date have evaluated the prognostic impact of sickle cell trait (SCT) and other inherited haemoglobinopathies, of which several are disproportionately high in the AA population. In a cohort analysis of treated patients diagnosed with breast or prostate cancer in the linked SEER-Medicare database, the relative risk (RR) for ≥1 serious adverse events (AEs), defined as hospitalisations or emergency department visits, was estimated for 371 AA patients with a haemoglobinopathy (AA+) compared to patients without haemoglobinopathies (17,303 AA-; 144,863 NHW-). AA+ patients had significantly increased risk for ≥1 AEs compared to AA- (RR = 1.19; 95% CI 1.11-1.27) and NHW- (RR = 1.23; 95% CI 1.15-1.31) patients. The magnitude of effect was similar by cancer type, and in analyses of AA+ with SCT only. Our findings suggest a novel hypothesis for disparities in cancer outcomes.

Objective: Adjuvant endocrine therapy (AET) significantly reduces risk of breast cancer recurrence in those patients whose tumor tests hormone (estrogen and/or progesterone) receptor positive. Many who are prescribed AET do not adhere adequately. Studies have sought to examine the effects of interventions to enhance patients' AET adherence, with strikingly mixed results. In order to reconcile a disparate literature, this paper aims to (1) quantitatively review the aggregate effect of interventions designed to optimize AET adherence within the current literature and (2) meta-analyze these effects across studies' by intervention design., Methods: Duplicate searches were conducted using multiple electronic databases as well as hand searches of recent year conference abstracts. Studies were included that (1) tested an intervention to promote AET adherence; (2) reported at least one measure of medication adherence; and (3) reported (or provided upon request) data sufficient to calculate effect size. Effect sizes were calculated using random effects models., Results: Seven studies representing eight unique interventions were included. We observed an overall null effect across all interventions (k = 8; d [95% CI] = 0.28 [-0.05, 0.61]); however, sensitivity analyses showed that interventions that used bi-directional communication showed statistically significant effects relative to control groups within each study (k = 4; d [95% CI] = 0.59 [0.23, 0.95]) while those relying only on providing information to the patient (one-way communication) did not (k = 4; d [95% CI] = -0.03 [-0.27, 0.20])., Conclusions: Interventions that promote patient self-report may improve AET adherence through enhancing patient engagement. Investigators and clinicians who wish to optimize medication adherence in this population can consider this approach., (© 2018 John Wiley & Sons, Ltd.)

Purpose: To improve the care of survivors of head and neck cancer, we developed the Head and Neck Survivorship Tool: Assessment and Recommendations (HN-STAR). HN-STAR is an electronic platform that incorporates patient-reported outcomes into a clinical decision support tool for use at a survivorship visit. Selections in the clinical decision support tool automatically populate a survivorship care plan (SCP). We aimed to refine HN-STAR by eliciting and incorporating feedback on its ease of use and usefulness., Methods: Human-computer interaction (HCI) experts reviewed HN-STAR using think-aloud testing and the Nielsen Heuristic Checklist. Nurse practitioners (NPs) thought aloud while reviewing the clinical decision support tool and SCP and responded to an interview. Survivors used HN-STAR as part of a routine visit and were interviewed afterward. We analyzed themes from the feedback. We described how we addressed each theme to improve the usability of HN-STAR., Results: Five HCI experts, 10 NPs, and 10 cancer survivors provided complementary usability insight that we categorized into themes of improvements. For ease of use, themes included technical design considerations to enhance user interface, ease of completion of a self-assessment, streamlining text, disruption of the clinic visit, and threshold for symptoms to appear on the SCP. The theme addressing usefulness was efficiency and comprehensiveness of the clinic visit. For each theme, we report revisions to HN-STAR in response to the feedback., Conclusion: HCI experts provided key technical design insights into HN-STAR, whereas NPs and survivors provided usability feedback and clinical perspectives. We incorporated the feedback into the preparation for additional testing of HN-STAR. This method can inform and improve the ease of use and usefulness of the survivorship applications.

Purpose This guideline provides recommendations on the management of adults after head and neck cancer (HNC) treatment, focusing on surveillance and screening for recurrence or second primary cancers, assessment and management of long-term and late effects, health promotion, care coordination, and practice implications. Methods ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. The American Cancer Society (ACS) HNC Survivorship Care Guideline was reviewed for developmental rigor by methodologists. An ASCO Expert Panel reviewed the content and recommendations, offering modifications and/or qualifying statements when deemed necessary. Results The ASCO Expert Panel determined that the ACS HNC Survivorship Care Guideline, published in 2016, is clear, thorough, clinically practical, and helpful, despite the limited availability of high-quality evidence to support many of the recommendations. ASCO endorsed the ACS HNC Survivorship Care Guideline, adding qualifying statements aimed at promoting team-based, multispecialty, multidisciplinary, collaborative head and neck survivorship care. Recommendations The ASCO Expert Panel emphasized that caring for HNC survivors requires a team-based approach that includes primary care clinicians, oncology specialists, otolaryngologists, dentists, and other allied professionals. The HNC treatment team should educate the primary care clinicians and patients about the type(s) of treatment received, the likelihood of potential recurrence, and the potential late and long-term complications. Primary care clinicians should recognize symptoms of recurrence and coordinate a prompt evaluation. They should also be prepared to manage late effects either directly or by referral to appropriate specialists. Health promotion is critical, particularly regarding tobacco cessation and dental care. Additional information is available at www.asco.org/HNC-Survivorship-endorsement and www.asco.org/guidelineswiki .

Purpose: Although breast cancer survivors' lifestyle choices affect their subsequent health, a majority do not engage in healthy behaviors. Because treatment end is a "teachable moment" for potentially altering lifestyle change for breast cancer survivors, we developed and tested two mail-based interventions for women who recently completed primary treatment., Methods: One hundred seventy-three survivors were randomly assigned to (1) Targeting the Teachable Moment (TTMI, n = 57), (2) Standard Lifestyle Management (SLM, n = 58), or (3) usual care (UC, n = 58) control group. Participants who were assigned to TTMI and SLM received relevant treatment materials biweekly for 4 months. Participants were assessed at baseline (T1, before randomization), post-treatment (T2, 4 months), and follow-up (T3, 7 months). Fruit and vegetable (F/V) intake, fat intake, and moderate-to-vigorous physical activity (MVPA) were assessed., Results: Results showed promise for these mail-based interventions for changes in health behaviors: Survivors in TTMI (+.47) and SLM (+.45) reported increased F/V intake, whereas those in UC (-.1) reported decreased F/V intake from T1 to T2. Changes in minutes of MVPA from T1 to T2 were higher in SLM than UC and marginally higher in TTMI than UC. However, these differences were due to decreased MVPA in UC rather than increased MVPA in the intervention groups. There were no group differences regarding fat intake. Survivors reported high satisfaction and preference for mail-based interventions, supporting feasibility., Conclusions: Mail-based lifestyle interventions for breast cancer survivors may benefit F/V intake and physical activity. Further testing and optimizing of these interventions is warranted.

Background: Head and neck cancer survivors commonly experience severe long-term toxicities, late-occurring symptoms, and significant risks of the second primary malignancy and comorbid illnesses. With multiple simultaneous health issues, these complex cancer survivors often do not receive comprehensive health care that addresses their needs. A tool is needed to streamline and standardize comprehensive care for this cohort., Methods/design: We designed the Head and Neck Survivorship Tool: Assessment and Recommendations (HN-STAR) to address health care challenges for head and neck cancer survivors. HN-STAR is an electronic platform that aims to simplify the provision of personalized care in cancer survivorship clinics. It uses an algorithmic approach to integrate patient-reported outcomes, clinical details, and evidence-based guidelines to standardize comprehensive care provided in routine survivorship visits. It has four integrated components: (1) a simplified treatment summary , which pulls treatment details from a clinical database or can be completed manually using a streamlined form; (2) an online self-assessment for patients to report their own symptoms; (3) an interactive discussion guide presenting all relevant information to the provider during the clinic visit; and (4) a survivorship care plan generated at the end of each visit that reflects decisions made during the visit. By using a modifiable electronic platform, HN-STAR provides a method for incorporating survivorship care plans into clinical practice and for disseminating evidence on symptom management and preventive care. This is a study to assess the feasibility of a future multi-site, randomized clinical trial of HN-STAR. We will enroll head and neck cancer survivors who are followed in one of two nurse practitioner-led survivorship clinics. We will implement HN-STAR for one routine survivorship visits. We will assess (1) usability and feasibility outcomes of HN-STAR from the perspective of key stakeholders and (2) the planned outcomes intended for the larger trial. We will collect usability and feasibility data from online surveys of survivors and their providers. Our findings will inform whether it is feasible to advance HN-STAR to trial. If so, we will adapt HN-STAR and the study design of the trial in response to feedback from survivors and providers. The long-term goal is to determine if such an intervention will lead to improved and simplified comprehensive survivorship care., Discussion: This feasibility study will evaluate implementation of HN-STAR into clinical practice in terms of usability, practicality, and clinical flow in two distinct clinical settings. This study will also provide critical baseline data to characterize this vulnerable population. Findings from this study will inform a multicenter randomized trial of HN-STAR, aimed at standardizing and streamlining the delivery of evidence-guided comprehensive care for head and neck cancer survivors. Ultimately, if found effective, the modular structure of HN-STAR could permit its expansion to survivors of other complex cancers., Trial Registration: ClinicalTrials.gov, NCT02571673.

Purpose: The role of multidisciplinary care (MDC) on cancer care processes is not fully understood. We investigated the impact of MDC on the processes of care at cancer centers within the National Cancer Institute Community Cancer Centers Program (NCCCP)., Methods: The study used data from patients diagnosed with stage IIB to III rectal cancer, stage III colon cancer, and stage III non–small-cell lung cancer at 14 NCCCP cancer centers from 2007 to 2012. We used an MDC development assessment tool—with levels ranging from evolving MDC (low) to achieving excellence (high)—to measure the level of MDC implementation in seven MDC areas, such as case planning and physician engagement. Descriptive statistics and cluster-adjusted regression models quantified the association between MDC implementation and processes of care, including time from diagnosis to treatment receipt., Results: A total of 1,079 patients were examined. Compared with patients with colon cancer treated at cancer centers reporting low MDC scores, time to treatment receipt was shorter for patients with colon cancer treated at cancer centers reporting high or moderate MDC scores for physician engagement (hazard ratio [HR] for high physician engagement, 2.66; 95% CI, 1.70 to 4.17; HR for moderate physician engagement, 1.50; 95% CI, 1.19 to 1.89) and longer for patients with colon cancer treated at cancer centers reporting high 2MDC scores for case planning (HR, 0.65; 95% CI, 0.49 to 0.85). Results for patients with rectal cancer were qualitatively similar, and there was no statistically significant difference among patients with lung cancer., Conclusion: MDC implementation level was associated with processes of care, and direction of association varied across MDC assessment areas., (Copyright © 2015 by American Society of Clinical Oncology.)

Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist., Methods: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis., Results: Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH)., Conclusions: Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Objectives: Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck cancer (H&NC). OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to treatment interruptions. Based on the role of inflammatory pathways in OM pathogenesis, we investigated effect of cyclooxygenase-2 (COX-2) inhibition on severity and morbidity of OM., Methods: In this double-blind placebo-controlled trial, 40 H&NC patients were randomized to daily use of 200 mg celecoxib or placebo, for the duration of RT. Clinical OM, normalcy of diet, pain scores, and analgesic use were assessed 2-3 times/week by blinded investigators during the 6-7 week RT period, using validated scales., Results: Twenty subjects were randomized to each arm, which were similar with respect to tumor location, radiation dose, and concomitant chemotherapy. In both arms, mucositis and pain scores increased over course of RT. Intention-to-treat analyses demonstrated no significant difference in mean Oral Mucositis Assessment Scale (OMAS) scores at 5000 cGy (primary endpoint). There was also no difference between the two arms in mean OMAS scores over the period of RT, mean worst pain scores, mean normalcy of diet scores, or mean daily opioid medication use in IV morphine equivalents. There were no adverse events attributed to celecoxib use., Conclusions: Daily use of a selective COX-2 inhibitor, during period of RT for H&NC, did not reduce the severity of clinical OM, pain, dietary compromise or use of opioid analgesics. These findings also have implications for celecoxib use in H&NC treatment regimens (NCT00698204)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow-up care to address the myriad of long-term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow-up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow-up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long-term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility-specific and population databases., (© 2014 American Cancer Society.)

Background: The Institute of Medicine recommended that survivors of cancer and their primary care providers receive survivorship care plans (SCPs) to summarize cancer treatment and plan ongoing care. However, the use of SCPs remains limited., Methods: Oncology providers at 14 National Cancer Institute Community Cancer Centers Program hospitals completed a survey regarding their perceptions of SCPs, including barriers to implementation, strategies for implementation, the role of oncology providers, and the importance of topics in SCPs (diagnosis, treatment, recommended ongoing care, and the aspects of ongoing care that the oncology practice will provide)., Results: Among 245 providers (response rate of 70%), 52% reported ever providing any component of an SCP to patients. The most widely reported barriers were lack of personnel and time to create SCPs (69% and 64% of respondents, respectively). The most widely endorsed strategy among those using SCPs was the use of a template with prespecified fields; 94% of those who used templates found them helpful. For each topic of an SCP, although 87% to 89% of oncology providers believed it was very important for primary care providers to receive the information, only 58% to 65% of respondents believed it was very important for patients to receive the information. Furthermore, 33% to 38% of respondents reported mixed feelings regarding whether it was the responsibility of oncology providers to provide SCPs., Conclusions: Practices need additional resources to overcome barriers to implementing SCPs. We found resistance toward SCPs, particularly the perceived value for the survivor and the idea that oncology providers are responsible for SCP dissemination., (© 2013 American Cancer Society.)

Background: Routine colorectal screening, decreases in incidence, and advances in treatment have lowered colorectal cancer mortality rates over the past three decades. Nevertheless, it remains the second most common cause of cancer death amongst men and women combined in U.S. Most cases of colon cancer are diagnosed at a late stage leading to poor survival outcomes for patients. After extensive research of publically available data, it would appear that the state of Connecticut does not have available state-wide data on patient wait times for routine colonoscopy screening. Furthermore, there are no publicly available, or Connecticut-specific, reports on Medicaid participation rates for colorectal screening amongst gastroenterologists (GI) in Connecticut. In 2012, the American Cancer Society report on Colorectal Cancer Screening Rates confirmed barriers to health-care access and disparities in health outcomes and survival rates for colon cancer patients based on race, ethnicity, and low socioeconomic status. Given this information, one could conjecture that low Medicaid participation rates among GIs could potentially have a more severe impact on health-care access and outcomes for underserved populations. At present, funding and human resources are being employed across the state of Connecticut to address bottlenecks in colorectal cancer screening. More specifically, patient navigation and outreach programs are emerging and expanding to address the gaps in services for hard-to-reach populations and the medically underserved. Low Medicaid participation rates and increased wait times for colonoscopy screening may impair the efficacy of colorectal cancer patient navigation and outreach efforts and potentially funding for future interventions. In this study, we report the results of our secret-shopper telephone survey comprising of 93 group and independent gastroenterologist (GI) practices in different counties of Connecticut., Methods: Reviewing online resources and yellow pages, researchers compiled a county-specific list of GI practices throughout Connecticut and conducted a secret-shopper survey by telephone. A standard script and set of questions was formulated and used for each telephone call to GI practices. Data was analyzed in context of statistics available to the public at large from the U.S. Census Bureau., Results: Overall, 46% of all 93 practices and 62% of individual GIs from all 93 practices state-wide reported Medicaid participation. About 35% of surveyed practices were independent practices; 41% of these reported Medicaid participation. About 65% of surveyed practices were group practices; 49% of these reported Medicaid participation. Approximately, 85% of all practices are in Fairfield, Hartford, orNew Haven counties. Of all three counties, New Haven reported the highest Medicaid participation rate by practices; 62% of all practices in New Haven reported participation. Fairfield reported the lowest Medicaid participation rate by practices; 29% of all practices in Fairfield reported participation. When Medicaid participation rates were calculated for total number of gastroenterologists from all practices in a given county (as opposed to participation rates by number of practices), Medicaid participation rates were 80% and 44% for New Haven and Fairfield, respectively. Of all practices in Hartford, only 50% reported Medicaid participation, whereas 67% of the total number of gastroenterologists (as opposed to practices) reported Medicaid participation. According to a recent national survey, 47% of gastroenterologists reported stopping accepting new Medicaid patients. Overall minimum and maximum wait times were reported to be the highest for Hartford, but wait times were long even for smaller counties, reflecting a possible imbalance in supply and demand or inefficiency in allocating the available resources., Conclusions: Only a limited number of gastroenterology practices in Connecticut accept Medicaid patients, notably in selected counties, but in all counties, and this may add to access barriers. It is yet unclear whether these disparities are significant enough to create a supply-demand imbalance and thus, have a significantly negative impact on health outcomes for the underserved. Nevertheless, with the high unemployment rates and impending implementation of mandated state-wide health-care reform as outlined in the Affordable Care Act, the Medicaid population in the state of Connecticut will increase, increasing future demand for services. In addition, based on the survey findings, longer wait times for colonoscopy screening are reported for the many of GI practices in Connecticut for Medicaid-insured as well as non-Medicaid patients. Longer wait times may have an impact on patient compliance, especially for the underserved populations that are hard to reach and ensure follow-up, contributing to potential delayed diagnosis. A Medicaid-associated disparity in this area will serve to exacerbate the problem for the underserved compared to those relatively well served. Those currently not seeking screening are at even higher risk of contributing to the higher mortality rate, and we need to find out how best to ensure that we can more uniformly apply screening and have the capacity to do so.

Although general guidelines have been developed for triage of victims in the field and for hospitals to plan for a radiologic event, specific information for clinicians and administrators is not available for guidance in efficient management of radiation victims during their early encounter in the hospital. A consensus document was developed by staff members of four Connecticut hospitals, two institutions of higher learning, and the State of Connecticut Department of Environmental Protection and Office of Emergency Preparedness, with assistance of the American Society for Therapeutic Radiology and Oncology. The objective was to write a practical manual for clinicians (including radiation oncologists, emergency room physicians, and nursing staff), hospital administrators, radiation safety officers, and other individuals knowledgeable in radiation monitoring that would be useful for evaluation and management of radiation injury. The rationale for and process by which the radiation response plan was developed and implemented in the State of Connecticut are reviewed. Hospital admission pathways are described, based on classification of victims as exposed, contaminated, and/or physically injured. This manual will be of value to those involved in planning the health care response to a radiologic event.

A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented.

The success of bone marrow transplantation depends not only on the engraftment of adequate numbers of hematopoietic stem cells but also on their self-renewal capacity, which must be sufficient to provide lifetime hematopoiesis. The lectin peanut agglutinin (PNA), when exposed to bone marrow, causes separation into two distinct fractions. The agglutinated fraction not only is enriched with colony-forming units--spleen but also is devoid of graft-versus-host (GVH) activity when injected into allogeneic lethally irradiated recipients, and therefore, it is considered to be an ideal source for bone marrow transplantation. The absence of GVH activity is presumably due to the separation of mature thymocytes into the nonagglutinated fraction and functionally immature thymocytes into the agglutinated fraction. Although there has been speculation that immature hematopoietic stem cells also selectively bind to PNA, other evidence suggests that the relationship of lectin binding specificity to level of maturity varies in different tissues. This study was performed to assess the self-renewal capacity of lectin-separated bone marrow stem cells. Results indicate that the self-renewal of the agglutinated fraction is significantly lower than that of the unfractionated bone marrow; such self-renewal of the nonagglutinated fraction is higher. This is further evidence for the heterogeneity of the stem cell pool. Stem cell enrichment should not be the goal in bone marrow transplantation; rather, the goal should be utilization of stem cells with the greatest self-renewal potential.

Reversible brachial plexopathy has occurred in very low incidence in patients with breast carcinoma treated definitively with radiation therapy. Of 565 patients treated between January 1968 and December 1979 with moderate doses of supervoltage radiation therapy (average axillary dose of 5000 rad in 5 weeks), eight patients (1.4%) developed the characteristic symptoms at a median time of 4.5 months after radiation therapy. This syndrome consists of paresthesias in all patients, with weakness and pain less commonly seen. The symptom complex differs from other previously described brachial plexus syndromes, including paralytic brachial neuritis, radiation-induced injury, and carcinoma. A possible relationship to adjuvant chemotherapy exists, though the etiology is not well-understood. The cases described demonstrate temporal clustering. Resolution is always seen.