Joan E. Cunningham

Case report of a patient with chemotherapy-induced peripheral neuropathy treated with manual therapy (massage)

PurposeChemotherapy-induced peripheral neuropathy (CIPN) is a common, miserable, potentially severe, and often dose-limiting side effect of several first and second-line anti-cancer agents with little in the way of effective, acceptable treatment. Although mechanisms of damage differ, manual therapy (therapeutic massage) has effectively reduced symptoms and improved quality of life in patients with diabetic peripheral neuropathy.MethodsHere, we describe application of manual therapy (techniques of effleurage and petrissage) to the extremities in a patient with grade 2 CIPN subsequent to prior treatment with docetaxel and cisplatin for stage III esophageal adenocarcinoma. Superficial cutaneous temperature was monitored using infrared thermistry as proxy for microvascular blood flow.ResultsBy the end of the course of manual therapy without any change in medications, CIPN symptoms were greatly reduced to grade 1, with corresponding improvement in quality of life. Improvements in superficial temperature were observed in fingers and toes.ConclusionsManual therapy was associated with almost complete resolution of the tingling and numbness and pain of CIPN in this patient. Concurrently increased superficial temperature suggests improvements in CIPN symptoms may have involved changes in blood circulation. To our knowledge, this is the first report of using manual therapy for amelioration of CIPN.

Correlation of sonographic features of invasive ductal mammary carcinoma with age, tumor grade, and hormone-receptor status.

To determine whether presenting sonographic features of invasive ductal carcinomas (IDC) are associated with patient age, tumor histologic grade, and hormonal receptor status.

Completion Node Dissection in Patients with Sentinel Node–Positive Melanoma of the Head and Neck

Objective. Determine if completion lymph node dissection (CLND) is associated with improved survival in sentinel lymph node (SLN)–positive cutaneous melanoma of the head and neck (CMHN) patients. Study Design. Retrospective analysis of large population database. Setting. Surveillance, Epidemiology and End Results (SEER) database/multiple settings. Subjects and Methods. Using the SEER database, the authors identified patients with SLN-positive CMHN. Clinicopathologic data and 5-year disease-specific survival (DSS) were examined for patients who underwent sentinel lymph node biopsy (SLNB) alone vs SLNB + CLND. Results. Among 350 SLN-positive patients, 210 (60%) had SLNB + CLND, and 140 (40%) had SLNB only. Patients in the SLNB-only group were significantly older (median age 62 vs 53 years, P < .0001). The cohort as a whole did not significantly benefit from CLND; however, CLND was associated with improved DSS for a subgroup of patients age <60 years with nonulcerated tumors ≤2 mm thick (P = .03). Relative to SLNB alone, CLND did not improve survival for patients age ≥60 years or those with thicker (>2 mm) or ulcerated tumors. Conclusions. Compared with SLNB alone, CLND does not seem to be associated with improved survival for most patients with SLN-positive CMHN. CLND likely improves survival for patients age <60 years with thin (≤2 mm) nonulcerated tumors and when there is a low risk of identifying positive non-SLNs.

Completion Lymph Node Dissection Based on Risk of Nonsentinel Metastasis in Cutaneous Melanoma of the Head and Neck

Objective Theoretically, completion lymph node dissection (CNLD) should have the lowest benefit in the absence of nonsentinel lymph node (NSLN) metastases. For this reason, substantial research efforts have attempted to define specific criteria that are associated with a low-enough risk of NSLN positivity so that CLND can be deferred. Our objectives were (1) to identify features associated with low risk of NSLN positivity in sentinel lymph node–positive cutaneous melanoma of the head and neck (CMHN) and (2) to analyze the effect of CLND on 5-year disease-specific survival (DSS) among subgroups stratified by risk of NSLN metastasis. Study Design Retrospective analysis of population-based data. Setting SEER database. Subjects and Methods Patients with sentinel lymph node–positive CMHN were categorized according to lymph node treatment following sentinel lymph node biopsy (SLNB): 210 underwent CLND and 140 deferred. Clinicopathologic characteristics and survival were compared between SLNB+CLND and SLNB-only groups. Survival analyses were stratified by age and characteristics associated with NSLN positivity. Results Minimal tumor thickness and nonulceration were associated with lowest risk of positive NSLN (P < .025). In the subgroup with the lowest risk of metastasis, patients aged <60 years who underwent CLND+SLNB had markedly better DSS than those receiving SLNB only (>90% vs <25%; P < .0025). Paradoxically, in subgroups with a higher risk of NSLN metastasis, DSS was similar whether CLND was performed or not (P > .25). Conclusions Selecting patients for CLND according to risk of NSLN metastasis may be a suboptimal strategy for improving DSS. We believe that CLND should not be withheld on the basis of “low risk” features in CMHN.

Abstract CT122: RCT of an herbal mouthrinse for radiotherapy induced oral mucositis in cancer patients

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Objectives: Primary aim of the ongoing study ([NCT01898091][1]) is to determine whether a mouthrinse containing extract of neem leaf (Azadirachta indica A. Juss.), a tropical evergreen tree with anti-inflammatory and anti-microbial medicinal properties, will lessen the severity of oral mucositis (OM) in patients undergoing radiation therapy (RT) to the head and neck. Secondary aims are to assess the effects of the neem mouthrinse on the microbial environment of the oral cavity and on quality of life. Methods: Design is a double-blind, controlled, randomized, parallel-group Phase II clinical trial at a single NCI designated center. Block-randomization was used for patient assignment, stratified by tobacco use. Eligibles were adults with histologically confirmed head and neck cancer (HNC) whose treatment includes RT for 7 weeks. HNC includes malignancy of the oral cavity, oro-pharynx and larynx (ICD-9 codes 140 - 149, 161; ICD-O morphology code of 2 or 3). Exclusion criteria include prior HNC radiotherapy, baseline mouth and throat soreness (MTS) score of >3, ECOG performance status >2, allergy or inability to use mouthrinse, and language barrier. Evaluable participants receive > 40 Gy RT and participate to week 6 RT. Study duration is 12 weeks with visits at baseline, weekly during RT, 3 telephone visits post RT, and one-month follow-up visit. Data were collected using the Oral Mucositis Daily Questionnaire, Functional Assessment of Cancer Therapy-Head and Neck, and Symptom Distress Scale questionnaires; CariScreen for oral microbial load, and ELISA and flow cytometry for salivary analyte measures. Results: Of 53 patients enrolled, 3 screen failed and 8 withdrew leaving 42 with evaluable data. Neem (n = 23) and placebo (n = 19) groups were not statistically different for demographic and clinical variables. Major hypothesis assessed as the maximum change in MTS score from baseline during 6 weeks of RT resulted in a larger change, 1.91 with SD 1.34 for neem group vs. 1.71 with SD 1.29 for placebo group based on a Wilcoxon rank sum test with one-sided alpha = 0.05. Preliminary results suggest no difference in the maximum change in severity from baseline (p = 0.85). Neem group had higher adherence to mouthrinse protocol measured as ≥4 days mouthrinse use per week for six weeks (OR 2.56, p = 0.19). Additional outcomes of ongoing comparisons across groups include time to maximum OM severity, time to onset of OM, percent of patients with MTS scores <3, and percent of patients by levels of change in MTS score. Regression analyses will be used to assess relationships between maximum and temporal changes in MTS score and mouthrinse group, adjusted for baseline characteristics and pertinent events. Relationships between changes in MTS score and mouthrinse usage over the time-course of the study will also be explored by graphical comparisons and regression approaches. Time to event outcomes will be assessed using Kaplan-Meier curves and comparisons will be made by log rank tests. Due to sample size, these latter analyses will be exploratory. Citation Format: Susan G. Reed, Joan E. Cunningham, Elizabeth Garrett-Mayer, Jennifer L. Mulligan, Laura D. Fields, Lynsey R. Boyle, Sarah P. Daanen, John H. Keller, Casey L. Roach, Whitney C. Pasquini, Lauren Lawrence, Howell Harmon, Ahmad R. Garrett, Michael J. Wargovich, Anand K. Sharma. RCT of an herbal mouthrinse for radiotherapy induced oral mucositis in cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT122. doi:10.1158/1538-7445.AM2015-CT122 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01898091&atom=%2Fcanres%2F75%2F15_Supplement%2FCT122.atom

Abstract P1-09-20: Evaluating alcohol and tobacco use in an ethnically diverse sample of breast cancer patients: Implications for survivorship

Background/Objective: Data suggest that modifiable risk factors such as alcohol and tobacco use may increase the risk of breast cancer (BC) recurrence and reduce survival. According to 2012 data from the Centers for Disease Control (CDC) and Prevention Behavioral Risk Factor Surveillance System (BRFSS), 4.8% of women in South Carolina (SC) are heavy drinkers (>1 drink/day) with 9.6% having ≥4 drinks at least once in the past month (US state medians are 5.2% and 11.4%); 19.1% are current smokers (US state median 17.4%). Female BC mortality in SC is almost 50% higher in African Americans (AAs) than in European Americans (EAs; 27.5/100,000 and 19.1%, respectively). In SC, there is an AA subpopulation, the Sea Islanders, who carry the lowest AA rate of European genetic admixture. Given the substantial racial survival disparity we examined the patterns of alcohol and tobacco use in an on-going, ethnically diverse statewide study of women with recently diagnosed breast cancer. Methods: Participants were identified within 18 months post-diagnosis through the SC Central Cancer Registry (SCCCR). Women who opted into the study were interviewed via telephone, self-reporting data including race/ethnicity, educational status, alcohol consumption and tobacco use during the past 30 days. Published CDC guidelines were used to categorize alcohol and tobacco use. Results: During the first 24 months of recruitment, 172 women ages 38 to 90 years have opted into our study; 139 were interviewed (43 EAs and 96 AAs) and results analyzed. AAs were slightly younger (p=0.066) and tended to have less education (statistically not significant: p=0.114) Alcohol: The minority of participants self-identified consuming alcohol (29.0%). Heavy use was infrequent: two (1.4%) reported consuming on average >1 drink/day,and six (4.4%) consumed ≥4 drinks on any day. Alcohol consumption was less prevalent among AAs than EAs (p=0.025). Among those who consumed alcohol, usage did not differ between AAs and EAs. Tobacco: Smoking (daily or occasional) was reported by 7.5% of participants (AA vs EA: p=1.00). Alcohol and/or Tobacco: Use of alcohol and/or tobacco was 1.7 times as prevalent among EAs compared to AAs (47.6% vs 28.7%; p=0.032). Conclusions: Compared to self-reported state data few participants reported heavy alcohol consumption or current tobacco use, particularly AAs, but 34.6% of participants do use alcohol or tobacco. While these findings suggest that alcohol and tobacco may not contribute to the racial disparities in breast cancer mortality observed in SC, it is nonetheless imperative to reduce these modifiable risk factors and improve breast cancer outcomes for all breast cancer survivors, regardless of race and ethnicity. Citation Format: Vivian J Bea, Joan E Cunningham, Dana R Burshell, Marvella E Ford. Evaluating alcohol and tobacco use in an ethnically diverse sample of breast cancer patients: Implications for survivorship [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-20.

Abstract A64: Evaluating the feasibility of a cancer registry-based recruitment strategy to obtain saliva samples for genetic association analysis in an ethnically diverse sample of breast cancer survivors

Introduction: African American (AA) women are disproportionately impacted by breast cancer mortality; this disparity may be related to their higher burden of triple-negative breast cancer. Despite the disparity, AA women participate in breast cancer research at lower rates than European American (EA) women. We have analyzed interim recruitment outcomes in an ongoing feasibility study of 90 women in South Carolina (SC) with recently diagnosed breast cancer, in which we are investigating the prevalence of genetic (saliva) markers which may be associated with risk of triple-negative breast cancer. Methods: In this ongoing study, recruitment proceeds in two phases. In Phase 1, the SC Central Cancer Registry (SCCCR) identifies AA and EA patients through the registry. The SCCCR mails a letter to each identified patient9s physician to obtain passive consent from the physician. After attainment of passive consent, the SCCCR director mails an introductory study letter to each identified patient. Then an AA SCCCR interviewer calls each patient to obtain active consent prior to sharing the patient9s contact information with Medical University of SC (MUSC) study staff. In Phase 2, MUSC study staff send a recruitment letter to each patient after which an AA MUSC interviewer administers a telephone-based eligibility screener. Eligible patients are invited to the study and are asked to return a signed consent form and saliva sample in separate postage paid envelopes. To evaluate the effectiveness of our recruitment protocol, we are monitoring participation rates of women from each ethnic group. Results: From April 2012 through August 2013, the SCCCR identified 387 patients (Phase 1), of whom 172 opted in (44.4%) and were referred to MUSC for eligibility screening. One hundred and thirty-six women (79.1% of those referred) have completed screening interviews; 42 were ineligible due to stage of disease or ethnicity (30.9%) and 5 declined (3.7%). Of the 89 women eligible and willing to participate in the study, 78 (87.6%) have signed a consent form and thus far 66 of them (84.6%) have provided saliva samples. Overall, recruitment and retention rates are very similar for EAs and AAs. However, ethnic differences in refusal rates are apparent at different points in the recruitment process. In Phase 1, we found that AAs were more likely to opt out, not able to be contacted, or passively refuse during the SCCCR recruitment activities (55.4% AAs vs. 41.7% of EAs). In Phase 2, EAs were more likely to actively or passively refuse after agreeing to be contacted by MUSC staff (10.9% of AAs vs. 27.4% EAs). We are continuing to monitor this trend. Recruitment of AAs and EAs is nearly complete, with saliva samples collected thus far from 37 AA and 29 EA women. Conclusions: The study results demonstrate the success of our two-phase cancer registry-based method to identify and recruit participants. The strength of this strategy is shown by the similar numbers of AAs and EAs recruited to this genetic study. On a broader level, increasing numbers of women in the US are diagnosed annually with breast cancer. Therefore, it is critical to identify genetic markers for this disease and to develop effective recruitment strategies to enhance the diversity of participants in genetic research. Our study methods pave the way for future large-scale recruitment strategies. Citation Format: Marvella E. Ford, Dana Burshell, Rita M. Kramer, Anthony J. Alberg, Debbie C. Bryant, Colleen E. Bauza, Tonya R. Hazelton, Catishia Mosley, Susan Bolick, Deborah Hurley, Emily Kistner-Griffin, Joan E. Cunningham. Evaluating the feasibility of a cancer registry-based recruitment strategy to obtain saliva samples for genetic association analysis in an ethnically diverse sample of breast cancer survivors. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr A64. doi:10.1158/1538-7755.DISP13-A64

Abstract P5-12-11: Evaluating overweight/obesity and physical activity rates in an ethnically diverse sample of breast cancer survivors

Introduction: Overweight/obesity are associated with higher risk of recurrence and poorer survival after a breast cancer diagnosis. According to The Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System (BRFSS) data for 2011, in South Carolina, 74.6% of African American (AA) and 62.5% of European American (EA) adult women are overweight/obese. Methods: Prevalence of overweight/obesity and level of physical activity (PA) are evaluated in an ongoing, ethnically-diverse statewide study of adult women with recently-diagnosed invasive breast cancer. Participants are identified within 18 months post-diagnosis through the South Carolina Central Cancer Registry (SCCCR). Participants who opt in to the study are interviewed via telephone and self-report their body weight, height and physical activities. Published CDC body mass index (BMI) categories and 2008 PA guidelines are used to characterize BMI and PA guideline adherence. Results : During the first 10 months of the study, 98 women (56 AA, 42 EA) were interviewed and results analyzed. Age: Participants ranged in age from 26 to 90 years (mean 60.2 years, SD 12.8), with AAs 3.7 years younger than EAs (p = 0.16). Education: Almost two-thirds of participants (61%) had more than a high school diploma (55% of AAs and 69% of EAs, p = 0.29). BMI: The BMI mean was 30.1 (SD 6.6, median 26.6) which was significantly higher in AAs (31.3 compared to 28.6 in EAs, p = 0.04). Among all women combined, 79% were overweight/obese, with no statistically significant difference by race (p = 0.15). Overweight was equally frequent among AAs (34%) and EAs (33%). However, obesity was more frequent among AAs (50%) than EAs (38%). Physical Activity (PA): CDC guideline adherence of ≥150 minutes/week of moderate PA was reported by only 32% of participants (25% of AAs, 41% of EAs; p = 0.10). A total of 28% reported no physical activity (30% of AAs and 24% of EAs, p = 0.47). Meeting CDC PA guidelines was associated with lower risk of being overweight/obese (OR = 0.41, p = 0.080), but this was statistically significant only among EAs (OR = 0.21, p = 0.035). Conclusions: Prevalence of overweight/obesity is high, regardless of ethnicity, and physical activity is low in this group of breast cancer survivors. It is imperative to identify effective strategies to reduce overweight and obesity, and to increase PA, in order to reduce the risk of recurrence and improve survival. In this regard, the study team is developing an National Institutes of Health R01 grant application to evaluate the effectiveness of an intervention, which combines a reduced-energy diet with increased PA, in reducing levels of cancer-related inflammatory biomarkers linked to breast cancer recurrence. Updated results of our on-going study, including associations of BMI and PA with breast cancer stage and phenotype, will be presented. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-11.

Abstract B48: Design of a feasibility study of breast cancer candidate genes in three ethnic groups.

The purpose of this presentation is to highlight the design and preliminary recruitment outcomes of a translational feasibility study to investigate the impacts of selected genetic single nucleotide polymorphisms (SNPs) on ethnic disparities in breast cancer subtypes, defined by ER, PR, and Her2 expression, associated with higher breast cancer mortality rates. The study will investigate the frequencies of five SNPs in the 19p13 locus of BRCA1 and two SNPs on chr 5p12 in three ethnic groups: African Americans with Sea Island ancestry (SI; all four grandparents were born in SI geographic regions), African Americans without known Sea Island ancestry (AA; 0 grandparents were born in SI geographic regions), and European Americans (EA). The SI population is an AA subpopulation indigenous to the coastal southeast that has the lowest rates of European genetic admixture of AA tested.(1,2) Comparing risk alleles across these three ethnic groups provides a novel paradigm to assess the extent to which SI ancestry and social processes such as acculturation may be linked to breast cancer subtypes associated with poor prognosis. A protocol has been developed to identify, contact and recruit women recently diagnosed with breast cancer within each ethnic group. Breast cancer cases are initially ascertained through the South Carolina Central Cancer Registry (SCCCR). Recruitment methods encompass steps taken at the SCCCR that include passive consent from the physician of record to contact identified patients, followed by active consent from the identified patients prior to contact by study staff. An investigator-developed algorithm developed to determine SI ancestry of patients, based on geographic ancestry, is administered and eligible participants are asked to complete a telephone-administered survey and to provide a saliva sample for genetic analysis. Recruitment began in June 2012. To date, 23 participants have been recruited, of whom 6 are AA (26%) and 17 are EA (74%), with a mean age of 57.5 years (range =39-77 years). Recruitment will continue until 30 women in each ethnic group are enrolled (total 90 participants). The recruitment process is monitored using a CONSORT diagram. This work will ultimately identify loci for further investigation of breast cancer disparities in other groups and for future development of targeted clinical therapies. References: 1. Divers, J, Sale MM, Lu L, et al. The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for Type 2 diabetes: the Sea Islands Genetic African American Registry (Project SuGAR). Journal of Lipid Research 2009;51:586-597. PubMed PMID: 9783527; PubMed Central PMCID: PMC2817588. 2. McLean DC, Jr., Spruill I, Argyropoulos G, et al. Mitochondrial DNA (mtDNA haplotypes reveal maternal population genetic affinities of Sea Island Gullah-speaking African Americans. American Journal of Physical Anthropology 2005;127:427-438. Citation Format: Marvella E. Ford, Joan E. Cunningham, Erika T. Brown, Ida J. Spruill, Anthony J. Alberg, Debbie C. Bryant, Karen D. Charles, Nestor F. Esnaola, Melanie S. Jefferson, Keith Whitfield, Rita M. Kramer, Susan Bolick, Deborah Hurley, Catishia Mosley, Tonya R. Hazelton, Vivian J. Bea, Dana R. Burshell, Shweta Singh, Emily Kistner-Griffin. Design of a feasibility study of breast cancer candidate genes in three ethnic groups. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B48.

SLNB and Outcomes in Cutaneous Melanoma of the Head and Neck

Objective: Among patients with cutaneous melanoma of the head and neck (CMHN) and ≥1 positive sentinel lymph node (SLN): 1) Determine if completion regional lymphadenectomy (RL) is associated with improved survival.2) Determine if survival differs between patients with 1 and >1 positive SLN. Method: Using the Surveillance Epidemiology and End Results (SEER) database, years 1998 to 2007, we identified 5,399 patients with primary CHNM who underwent excisional surgery and examination of ≥1 lymph node with follow-up >12 months. Clinicopathologic and outcomes data were examined using chi-square tests. Results: In preliminary analysis, 495 patients had 1 positive node and 387 had >1 positive node. Disease-specific survival (DSS) was statistically different between these 2 groups (64% and 47%), respectively, chi-square p1 node were involved (P = .112 and .891 respectively). Conclusion: In this simple preliminary analysis, CHNM patients with >1 positive lymph node had poorer survival compared with patients with a single positive lymph node. Among patients with SLN-positive CHNM, regional lymphadenectomy did not improve survival compared with patients who underwent SLNB alone. Formal survival analyses results will be presented.