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BACKGROUND: Pathologic complete response (pCR) or microinvasive residual breast cancer (ypTmic) following neoadjuvant chemotherapy (NAC) is critical for good long-term outcomes in triple negative breast cancer (TNBC) patients (pts) but is achieved only in 40-50% of pts. Its combination with pembrolizumab, the new standard of care in TNBC, increases the pCR rate to 65% but is associated with significant immune-related and permanent toxicities. Higher intratumoral levels of CD8+ cytotoxic T-lymphocytes (CTLs) and low levels of regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) predict improved relapse-free survival (RFS), overall survival (OS) and higher probability of pCR, a surrogate marker for RFS. Locally produced chemokines CCL5, CXCL9, CXCL10 and CXCL11 are critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction, with high CXCL9 expression being associated with a 3-fold higher rate of achieving pCR in response to NAC. Our preclinical data show that Chemokine-modulatory (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b and celecoxib (COX-2 inhibitor), selectively induces CTL-attractants but decreases MDSC- and Treg-attractants in the tumor microenvironment (TME). We hypothesized that the combination of CKM with paclitaxel will promote selective CTL infiltration into TNBC, and along with doxorubicin/cyclophosphamide (AC), will result in higher rate of pCR, translating into improved RFS and OS. METHODS: In the phase I study NCT04081389, 9 pts with stage I-III TNBC were enrolled with median age of 47 (37-55) years. All patients were treated with paclitaxel 80 mg/m2 IV weekly for 12 weeks, and for first 3 weeks days 1-3 also received CKM regimen consisting of rintatolimod 200 mg IV and celecoxib 200 mg oral twice daily. IFN-α2b was administered in an accelerated titration design at doses 0 or 5 million units (MU)/m2 [Dose Level (DL) 1,2 respectively] in first 2 pts (no intra-patient dose escalation), then 10 MU/m2 [DL 3] in 4 patients and then 20 MU/m2 [DL 4] in 3 patients. Pre- and 3 week-on treatment biopsies were performed at DL 3 and DL 4 (5 patients). This was followed by standard dose-dense AC and surgery. Dose-limiting toxicity (DLT) was defined as grade 3 or higher toxicity within the first 3 weeks of treatment. The primary endpoint was safety and tolerability, to determine the recommended phase II dose (RP2D) of CKM for extended efficacy study. The secondary endpoints included the efficacy (pCR), along with RFS and OS. Tumor and blood biomarkers were analyzed in exploratory studies. RESULTS: Treatment was well-tolerated with mostly grade 1 or 2 treatment-related adverse events (TRAEs) and no DLTs. Grade 3 TRAE were neutropenia (3/9), attributed to CKM (1/9) or paclitaxel (3/9), pneumonia (1/9) and anemia (1/9) attributed to AC. Two additional severe adverse events (pneumonia and squamous cell carcinoma of skin in situ) were observed, unrelated to study treatment. Paclitaxel- or AC-related toxicities were not higher than expected. There was no evidence of delayed or immune-related toxicities 90 days post-treatment. 5/9 (56%) pts attained pCR, and 1 additional pt had ypTmic at the time of surgery. There were no patients with progressive disease. All patients were able to get planned surgery with no additional delays observed. There was consistent (p=0.07) selective increase in CD8α (CTL marker) in on-treatment tumor biopsies with concomitant decrease in CD8α in the blood (p=0.04). CONCLUSIONS: The treatment was well-tolerated and no DLTs were observed and we determined RP2D for future studies. We observed promising clinical activity with pCR + ypTmic rate of 66%, comparable to pembrolizumab combination with NAC. A larger phase II study is being designed to confirm the observed efficacy and to determine if CKM regimen would be a safer short-term alternative to pembrolizumab or if CKM can overcome the resistance to the standard pembrolizumab/NAC therapy. Citation Format: Shipra Gandhi, Mateusz Opyrchal, Cayla Ford, Ronald Slomba, Kristopher Attwood, Tracey O’Connor, Ellis Levine, Pawel Kalinski. Preliminary indications of safety and efficacy of neoadjuvant chemotherapy plus chemokine-modulating regimen (rintatolimod, IFN-α2b, celecoxib) in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-07.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors’ complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

Background Patients (pts) with ER+ HER2+ breast cancer (BC) are less likely to achieve pathological complete response (pCR) after neoadjuvant chemotherapy with dual HER2 blockade than pts with ER- HER2+ BC. Endocrine therapy (ET) plus trastuzumab is effective in advanced ER+ HER2+ BC, but pCR rate is low in the neoadjuvant setting. Inhibition of CDK4/6 and HER2 results in synergistic reduction in cell proliferation in preclinical studies. We therefore combined ET with CDK4/6 inhibition and trastuzumab in ER+ HER2+ BC as a chemotherapy-sparing regimen. Methods We evaluated the efficacy of palbociclib, letrozole, trastuzumab (PLT) in the neoadjuvant setting for pts with stages II or III ER+ HER2+ BC. Primary endpoint was pCR after 16 weeks of therapy. We assumed null of 15% pCR and pCR ≥ 30% warrants further investigation. To achieve 80% power at 1-sided 0.05 significance, 48 pts were to be enrolled. Evaluable population included pts who completed Cycle (C) 1 unless discontinued due to treatment-emergent adverse events (TEAEs) prior to completing C1. All who received one dose on study were considered evaluable for toxicity. Biopsies were collected at baseline (BL), C1 day 15 (C1D15), and surgery for RNA sequencing and central Ki67 assessment, for PAM50 subtype distribution, complete cell cycle arrest (CCCA: Ki67 ≤2.7%) at C1D15 and surgery, and treatment induced signaling changes. Results Accrual stopped early due to futility. 26 pts accrued were evaluable for efficacy and toxicity. pCR (residual cancer burden- [RCB] 0) was 7.7% (95% CI 0.9 - 25.1%) and RCB 0/I was 38.5% (95% CI 20.2 - 59.4%). TEAEs (n= 337) were seen in all pts (71.5% grade [G] 1, 19.3% G2, 8.6% G3, 0.6% G4); the most common were leukopenia (7.7%), neutropenia (7.1%), anemia (5.9%). G3/4 TEAEs occurred in 19 pts (73.1%). Among the 19, incidence of G3/4 neutropenia was 50%, hypertension 26.9%, leucopenia 7.7%. TEAEs (hypertension, ventricular tachycardia, pulmonary edema) leading to treatment discontinuation were reported in 1 pt. Two pts had at least one SAE. No treatment-related deaths occurred. Pt reported outcomes using NCI PRO-CTCAE revealed no differences in appetite, nausea, respiratory symptoms, edema, palpitations, rashes and dry skin, or concentration from BL to end of C4. Pts had worsening hair loss from BL to end of C4. Ki67 analysis indicated CCCA in 78% at C1D15, compared to 18% at surgery after only P had been discontinued approximately 4 weeks prior to surgery. RNA sequencing was performed on available biopsies collected at BL (N=16), C1D15 (N=5), and surgery (N=2) from 16 pts. Among 16 BL samples, PAM50 subtyping identified 5 (31.3%) basal-like, 2 (12.5%) HER2-E, 6 (37.5%) Lum B, and 3 (18.8%) normal. Subtype switching to Lum A at C1D15 (N=3, 1 each with HER2-E, Lum B, and normal at BL) or normal (N=2, 1 basal and 1 HER2-E at BL) was observed. 161 genes were differentially expressed (FDR p Citation Format: Foluso O Ademuyiwa, Donald Northfelt, Tracey O'Connor, Ellis Levine, Jingqin Luo, Yu Tao, Jeremy Hoog, Marie Laury, Tracy Summa, Trish Hammerschmidt, Zhanfang Guo, Ashley Frith, Katherine Weilbaecher, Mateusz Opyrchal, Rebecca Aft, Katherine Clifton, Rama Suresh, Nusayba Bagegni, Ian S Hagemann, Cynthia X Ma. Phase 2 study of neoadjuvant palbociclib, letrozole, and trastuzumab in patients with ER+ HER2+ breast cancer (PALTAN) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-01.

PURPOSE: To examine the association between race and clinical outcomes (pathological complete response [pCR]; recurrence free survival [RFS], and overall survival [OS]) in patients diagnosed with triple-negative (TNBC) or HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: Patients who self-identified as non-Hispanic white (NHW) or non-Hispanic Black (NHB) and were diagnosed with Stage I-III TNBC (n=171 including 124 NHW and 47 NHB) and HER2-positive (n=161 including 136 NHW and 25 NHB) breast cancer who received NAC from 2000–2018 at Roswell Park Comprehensive Cancer Center were included. Associations of race with pCR and survival outcomes were evaluated using logistic and Cox regression models, respectively. RESULTS: There was no statistically significant difference in pCR between NHB and NHW patients with TNBC (31.9 vs 29.8%; OR: 1.11, 95% CI 0.54–2.29) or HER2-positive breast cancer (36.0 vs 39.7%; OR: 0.87, 95% CI 0.36–3.11). After controlling for potential confounders, including age, stage, treatment regimens, insurance status, and comorbidities, no statistically significant difference in OS or RFS was observed between NHB and NHW patients within either subtype. CONCLUSION: TNBC or HER2-positive breast cancer patients treated at a single academic center in Buffalo, NY, showed similar outcomes independent of patients’ race. Given the known genetic diversity of African American ancestry in the US, further studies investigating the interplay between race, geography and clinical outcomes are warranted.

As the global population rises, agriculture and industry are under increasing pressure to become more sustainable in meeting this growing demand, while minimizing impacts on global emissions, land use change, and biodiversity. The development of efficient and symbiotic local bioeconomies can help to respond to this challenge by using land, resources, and side streams in efficient ways tailored to the needs of different regions. Green biorefineries offer a unique opportunity for regions with abundant grasslands to use this primary resource more sustainably, providing feed for cows, while also generating feed for monogastric animals, along with the co-production of biomaterials and energy. The current study investigates the impact of a green biorefinery co-product, leaf protein concentrate (LPC), for input to a pig farm, assessing its impact on pig diets, and the extended impact on the bioenergy performance of the pig farm. The study found that LPC replaced soya bean meal at a 50% displacement rate, with pigs showing positive performance in intake and weight gain. Based on laboratory analysis, the resulting pig slurry demonstrated a higher biogas content and 26% higher biomethane potential compared with the control slurry. The findings demonstrate some of the local synergies between agricultural sectors that can be achieved through extended green biorefinery development, and the benefits for local bioeconomy actors.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors' complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor’s complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively ( P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

To systematically develop a farm safety intervention for farmer peer learning groups, to support safe working practice adoption. An iterative, multi-actor process was used, guided by the Interventi...

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors’ needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies.

Encouraging safe work practices (SWPs) is challenging in agriculture. Group-based social learning has effectively promoted SWPs and health behaviors in other occupations, and could be applied in agriculture (e.g., through farmer discussion groups (DGs)). In Ireland, dairy DG members are more likely to adopt novel technologies and practices, a relationship that might extend to SWPs. The extent of SWP adoption among Irish dairy farmers is unknown. This paper evaluates a 2018 baseline study of SWP implementation, conducted as part of a dairy DG-based intervention study.A paper-based survey of SWP implementation and safety self-perception was distributed to 1,220 farmers from 84 dairy DGs. For eight SWPs, associated with high-risk farm hazards (livestock, slurry, machinery, or tractors), farmers were asked how frequently they implemented these practices in the previous year, and how frequently they intended to do so next year (0: never, 1: rarely, 2: sometimes, 3: most of the time, 4: all of the time).Surveys were completed by 460 farmers. For the previous year, three SWPs, related to slurry, machinery, and tractor hazards, scored a median frequency of four. Four SWPs, related to livestock, slurry, and machinery hazards, scored a median frequency of three. The lowest median score (two) was for tractor exit behavior. Median intention scores matched or exceeded past frequency for all SWPs, while 73% intended to increase implementation of at least one SWP. Most (96%) considered themselves a "safe farmer."Farmers generally perceived themselves to be safe at work, which is reflected in their SWP implementation. Most farmers intended to increase SWP implementation, suggesting awareness of safety shortcomings and a desire to farm more safely.This study can inform farm safety promotion initiatives. The disconnect between farmers' safety self-perception and SWP implementation merits further research.

Background A study was initiated at Roswell Park Comprehensive Cancer Center to capture the real-world experience related to the use of CDK4/6 inhibitors (Ciclibs) for the treatment of metastatic hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-). Patients and Methods A total of 222 patients were evaluated who received CDK4/6 inhibitors in the period from 2015 to 2021. Detailed clinical and demographic information was obtained on each patient and used to define clinical and demographic features associated with progression-free survival on CDK4/6 inhibitor-based therapies. Results In this real-world analysis, the majority of patients received palbociclib as the CDK4/6 inhibitor with letrozole or fulvestrant as the predominant endocrine therapies. The median progression-free survival (PFS) in the letrozole (27.6 months) and fulvestrant (17.2 months) groups were comparable to that observed in clinical trials. As expected, age at start of the treatment and menopausal status influenced endocrine therapy utilization but were not associated with PFS. Patients with recurrent disease had shorter PFS (P = .0024) than those presenting with de novo metastasis. The presence of visceral metastasis trended toward shorter PFS (P = .051). Similarly, prior endocrine therapy (P = .003) or chemotherapy (P = .036) was associated with shorter PFS. Body mass index was not associated with PFS or with dose interruption and/or modification. While the number of minorities in this analysis is limited (n = 26), these patients as a group had statistically shorter PFS on treatment (P = .002). Conclusions The real-world progression-free survival with CDK4/6 inhibitors mimics that observed in the clinical trial. A number of clinical and demographic features were associated with PFS on CDK4/6 inhibitor-based therapy. Further studies are ongoing to validate these findings incorporating additional cancer centers.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Recruitment of minority participants to clinical trials, especially studies without therapeutic intent, has been historically challenging. This study describes barriers to and successes of recruitment and retention strategies to dietary studies. A flaxseed study was conducted in healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA) to assess associations between gut microbial community composition and host metabolism (NCT01698294). To ensure equitable participation by AA and EA women, multiple forms of recruitment were utilized, including advertisements, posters, e-mail, word of mouth, and community outreach. Successful recruitment and retention of AA women to the intervention depended upon the specific methods used. AA women compared with EA women were more likely to respond to direct recruitment and community-based methods, rather than general advertisements. However, once women expressed interest, similar rates of consent were observed for AA and EA women (AA and EA: 51.6% vs. 55.7%, respectively

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.

PURPOSE: Research by our group has shown that acupressure bands are efficacious in reducing chemotherapy-induced nausea (CIN) for breast cancer patients who expect nausea, and that their effectiveness in controlling CIN can largely be accounted for by patients’ expectations of efficacy, i.e., a placebo effect. The present research examined if the effectiveness of acupressure bands could be enhanced by boosting patients’ expectation of the bands’ efficacy. METHODS: 242 Chemotherapy-naïve patients with breast cancer who expected nausea were randomized. Arms 1 and 2 received acupressure bands, plus a relaxation MP3 and written handout that were either expectancy-enhancing (Arm 1) or expectancy-neutral (Arm 2). Arm 3 was the control without bands or MP3, and received standard care. All participants received guidelines specified antiemetics. RESULTS: Peak CIN for Arms 1, 2, and 3 on a 1–7 scale was 3.52, 3.55, and 3.87, respectively (p=0.46). Because no differences were observed between Arms 1 and 2 (primary analysis), we combined these two arms (intervention) and compared them to controls for the following analyses. Significant interaction was found between intervention/control and receiving doxorubicin-based chemotherapy (yes/no) and pre-treatment anxiety (high/low). Intervention patients receiving doxorubicin had lower peak CIN than controls (3.62 vs. 4.38; p=0.02). Similarly, intervention patients with high pre-treatment anxiety had a lower peak CIN than controls (3.62 vs. 4.62; p=0.01). CONCLUSIONS: In breast cancer patients undergoing chemotherapy and having high CIN expectation, acupressure bands combined with a relaxation recording were effective in reducing CIN for patients who received doxorubicin or had high anxiety.

Progress made in early cancer diagnosis and therapy has translated into increased longevity for patients with breast cancer. As survival has increased, the potential cardiotoxicity of cancer chemotherapy regimens has become an important issue for survivorship. Doxorubicin-induced cardiotoxicity has been demonstrated at a cumulative dose of ≤ 300mg/m2, with histopathological changes seen in endomyocardial biopsy tissue from patients receiving as little as 240mg/m2 of doxorubicin. Individual risk stratification and early detection of chemotherapy-induced cardiotoxicity are crucial to prevent irreversible cardiac dysfunction. There is accumulating evidence for the utility of echocardiographic indices such as left ventricular global longitudinal strain (GLS) in the detection of early chemotherapy induced cardiac injury. We have previously highlighted a predictive role of genetic polymorphisms in the carbonyl reductase 3 gene CBR3 in anthracycline-related cardiomyopathy following childhood cancer. Consistent with our prior work, we hypothesized that breast cancer patients homozygous for the CBR3 V244M G allele would exhibit worsening GLS following DOX treatment when compared with patients homozygous for the A allele. We recruited 138 patients with breast cancer receiving treatment with DOX (total cumulative dose: 240mg/m2). 72 patients received an echocardiogram analyzing global longitudinal strain by speckle tracking at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Patients were genotyped for variants associated with anthracycline-related toxicity. In agreement with our previous findings and hypothesis, our interim analysis suggested that patients homozygous for the CBR3 V244M G allele (CBR V244) exhibited GL changes at 6 months after DOX therapy suggestive of cardiotoxicity in comparison to individuals homozygous for the A allele (CBR3 M244) (-1.2 ±3.5 vs 1±1.6; mean±SEM, p=0.8 by Mann-Whitney test). Although the differences between CBR3 genotype groups are not significant at p Citation Format: Lang JK, Quinones AL, Hageman Blair R, Early AP, Levine EG, Opyrchal M, Blanco JG, O'Connor T. Association of CBR3 polymorphisms with an early change in cardiac function as assessed by left ventricular global longitudinal strain in breast cancer patients treated with doxorubicin [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-08.

Although a rare and challenging condition, cancer during pregnancy should promptly be identified and treated. Not only standards of care guidelines for the underlying disease are taken into account, but also fetal safety might be weighted for clinical decisions. Frequent lack of experience and knowledge about this condition could lead to late diagnosis, imprecise management, suboptimal treatment and fetal and maternal harm. Therefore, this review aims to summarize the current evidence regarding the epidemiology, clinical presentation, diagnostic workup, staging and treatment, including novel treatment modalities for patients diagnosed with cancer during pregnancy.

Background: Effective immune therapies depend on the presence of cytotoxic T-lymphocytes (CTLs) in the tumor microenvironment (TME). Our preclinical data showed synergy between TLR3 ligands and interferon-α (IFN-α) in reprogramming the TME, but not healthy tissues, to selectively enhance CTL attraction, providing rationale for their systemic application to enhance local CTL densities in “cold” tumors. The pilot study NCT03599453 evaluated the safety of systemic chemokine modulating regimen (CKM) composed of i.v. rintatolimod (Ampligen; selective TLR3 ligand) and IFN-α, and its ability to promote local CTL influx to mTNBC lesions. Methods: Six evaluable patients (33-75 years) with mTNBC received 6 doses of rintatolimod (200 mg i.v.), IFN-α (INTRON-A; 20MU/m2 i.v.) and COX-2 inhibitor (celecoxib; 2 x 200 mg, p.o.) over 2 weeks, with tumor biopsies obtained before (within 6 days) and after (within 5 days) CKM. All patients received follow-up pembrolizumab (200 mg, i.v, Q3 weeks). The primary endpoint was the change in the CTL marker CD8α in the TME with a planned interim analysis after 3 patients (α=0.03) and final analysis after 6 patients (α=0.084). Correlative studies analyzed additional markers of CTLs, regulatory T-cells (Tregs), and CTL- and Treg-attracting chemokines in the TME and blood. Results: Treatment was well tolerated with mostly grade 1/2 adverse events and one grade 3 clinically significant pneumonitis and immune thrombocytopenic purpura observed during follow up pembrolizumab treatment. We observed uniform increases of intratumoral type-1 immune markers upon treatment: CD8α mRNA (6.1-fold; p=0.034), GZMB (3.5-fold; p=0.058), ratios of CD8α/FOXP3 and GZMB/FOXP3 (5.7-fold; p=0.036, and 7.6-fold; p=0.024 respectively), and CTL attractants CXCL10 (2.6-fold; p=0.104) and CCL5 (3.3-fold; p=0.019), successfully meeting the primary endpoint. In contrast, neither Treg marker Foxp3 nor Treg attractants CCL22 or CXCL12 were enhanced. These TME changes were accompanied by transient decreases in circulating CD3+CD8+ CTLs and CD3-CD56+ NK cells (but not Tregs), selectively affecting the cells expressing CXCR3 (receptor for CXCL10), but not CCR4 or CXCR4 (receptors for CCL22 and CXCL12). Three patients had stable disease lasting 2.4, 2.5 and 3.8 months, as of September 1, 2021 cut-off. An additional patient had a partial response (breast auto-amputation) with massive tumor necrosis observed in the post-CKM biopsy. Conclusion: This proof-of-concept study shows that short-term systemic CKM followed by pembrolizumab is safe and selectively enhances local CTL infiltration in the TME, providing rationale for concurrent CKM and PD1 blockade in prospective phase II studies. Citation Format: Shipra Gandhi, Mateusz Opyrchal, Melissa Grimm, Ronald Slomba, Kathleen Kokolus, Sebastiano Battaglia, Kristopher Attwood, Adrienne Groman, Lauren Williams, Mary Lynne Tarquini, Paul Wallace, Kah Teong Soh, Tracey O'Connor, Amy Early, Ellis Levine, Igor Puzanov, Marc Ernstoff, Pawel Kalinski. Systemic rintatolimod and interferon-α2b selectively reprogram local tumor microenvironment in patients with metastatic triple negative breast cancer for enhanced influx of cytotoxic T-lymphocytes but not regulatory T-cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT145.

Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA). Participants consumed ~10 g/d ground flaxseed for 6 weeks and provided overnight urine collections and fecal samples before and after intervention. The gut microbiota was characterized using 16S rRNA gene sequencing and differences in microbial community composition compared by ethnicity and intervention status. We observed a significant difference in the composition of the microbiota measured as beta diversity (p &lt, 0.05) between AA and EA at baseline that was attenuated with FS consumption. Genera that were significantly associated with ENL production (e.g., Klebsiella, Lactobacillus, Slackia, Senegalimassilia) were unique to each group. Bacteria (e.g., Fusobacteria, Pyramidobacter and Odoribacter) previously associated with colorectal cancer and cardiovascular disease, both diet-related chronic diseases, were unique to either AA or EA and were significantly reduced in the FS intervention. This study suggests that ethnic variation in ENL metabolism may be linked to gut microbiota composition, and its impact on disease risk deserves future investigation.

Background Brain metastases develop in up to 50% patients with metastatic triple negative breast cancer (TNBC) and HER2+ BC and are an increasing source of morbidity and mortality. HER3, overexpressed in triple negative and HER2+ brain metastatic breast cancer (BMBC), is a resistance factor to HER2-targeted therapies and a driver of CNS metastasis. Disease progression is associated with loss of anti-HER2/3 immunity. We have demonstrated that alphaDC1 loaded with glioma-specific peptides induce intratumoral production of chemokines (CXCL9, CXCL10, CXCL11, CCL5) which attract CXCR3- and CCR5- expressing cytotoxic T-lymphocytes (CTLs) and T-helper 1 (Th1) cells to brain tumors, inducing clinical responses and long-term disease stabilization in patients with aggressive recurrent primary brain tumors. Our preclinical data show that Chemokine modulating (CKM) regimen [rintatolimod, interferon (IFN)-α2b and COX-2 inhibitor] also selectively attracts effector CTLs and Th1 cells (but not suppressive regulatory T-cells or myeloid-derived suppressor cells) into tumors. Importantly, CKM preferentially promotes CTL migration into tumor rather than healthy tissues, providing rationale for its systemic use. We hypothesize that anti-HER2/3 type 1 polarized DC1s in combination with CKM and anti-PD1 will result in improved Th1/CTL response against HER2/3 epitopes, reduce brain recurrence and systemic progression. Methods This is a phase II single-arm, non-randomized multicenter study (NCT04348747). Eligibility includes patients with triple negative and HER2+ BMBC ≥ 18 years, ECOG PS ≤ 1, normal marrow and organ function with asymptomatic untreated brain metastases who receive αDC1 q2 weeks x 3, with CKM [200 mg IV rintatolimod, IFN-α 20 million units/m2 IV, celecoxib 200 mg oral BID] on days 1-3 with second and third dose of αDC1, followed by pembrolizumab 200 mg IV. Thereafter, pembrolizumab is given every 3 weeks, along with αDC1 and CKM every 3 months as booster dose until disease progression, intolerable side effects or withdrawal from study, or up to 24 months. Baseline and 3-week post-CKM treatment peripheral (non-CNS) biopsies are required for six patients. Primary objective is CNS response rate (RR) using RANO-BM criteria. If no CNS response is observed after 12 patients, study will be terminated. If ≥ 1 response observed, then 9 more patients will be enrolled, for a total of 21 patients. If ≥ 3 CR observed, the proposed therapy will be considered promising for further study. Secondary objectives include non-CNS RR per RECIST v1.1, median CNS, non-CNS and overall progression-free survival, overall survival and safety. Analysis of change in intratumoral biomarkers is an exploratory objective. Results N/A Conclusions N/A Trial Registration NCT04348747 Ethics Approval The study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-19-04120.

Background Neoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS. Methods In this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner. Results N/A Conclusions N/A Trial Registration NCT04081389 Ethics Approval The study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

Objectives: Occupational safety and health (OSH) interventions emphasizing regulation or education have had limited success in reducing agricultural accidents and fatalities. There is a growing interest in sociocultural approaches to OSH promotion amongst farmers, such as peer learning groups (PLGs). The level of OSH engagement within farmer PLGs (e.g. dairy discussion groups (DDGs)) is unknown. This study evaluates Irish DDG engagement with OSH in 2016 to better understand how DDGs contribute to OSH promotion.Methods: A mixed-mode (online, postal, and telephone) retrospective survey of 121 DDG representatives (i.e. chairperson or long-term member) assessed voluntary OSH engagement in 2016, including the location, frequency, duration, and content of OSH discussions.Results: Representatives of 96 DDGs participated in the survey and met the survey criteria. Most DDGs discussed OSH to some extent in 2016 (96%), including sharing personal experiences of accidents and illnesses (89%) and close calls (82%). For 76 DDGs, at least one meeting in 2016 addressed specific hazard and risk management topics. Groups were diverse with respect to discussion frequency, duration, and topics discussed.Conclusion: Farmers actively engaged with OSH in most DDGs surveyed, suggesting dairy farmers value OSH discussions. The findings illustrate the role of DDGs in OSH promotion, as a space for farmer-led, peer-to-peer knowledge-sharing. Farm advisory (extension) services and OSH professionals can strengthen OSH engagement through tailored resources that reflect contemporary OSH knowledge and popular discussion approaches (e.g. experience-sharing).

Background: Older adults are less likely to be included in clinical trials leading to the approval of novel cancer treatments. The Institute of Medicine and ASCO have identified therapeutic phase II trials as a key research priority to increase the evidence base for older adults with cancer. While targeted therapies may represent a less toxic option for older patients, few trials have studied their tolerability and efficacy in older adults. Here, we present a phase II study (NCT01273610) of the combination of trastuzumab and lapatinib in older patients with HER2+ metastatic breast cancer (MBC), incorporating geriatric oncology principles in the study design. Methods: Patients age ≥ 60 years with MBC and any number of prior chemotherapy (CT) lines received trastuzumab (either 4mg/kg loading dose followed by 2mg/kg weekly or 8mg/kg followed by 6mg/kg q/3 weeks) plus lapatinib 1000 mg/m2 daily in 21-day cycles. Patients completed a pre-treatment geriatric assessment including measures of function, comorbidity, cognition, nutrition, and psychosocial status. A toxicity risk score developed for older adults receiving cytotoxic CT was calculated for each patient (Hurria et al. JCO 2011 & 2016). Relationships between tolerability (dose reductions and grade (G) ≥ 3 toxicity attributed to treatment) and risk score analyzed using a log2 transformation were assessed using generalized linear models, Student's t tests, and Fisher's exact test. Response rate (RR) and progression free survival (PFS) were evaluated. Results: 40 patients (mean age 72 [60-92]) were accrued from 04/11 to 05/15. 25% (n = 10) were ≥ 75 years of age. 65% of patients (n = 26) had HR+ tumors and 35% (n = 14) were receiving ≥ 3rd line treatment. Median number of cycles was 4 (0-28). RR was 23% (n = 9, 95% CI 11-38%; 1 complete, 8 partial). 23% (n = 9) achieved stable disease. PFS was 2.7 months (95% CI 2.5-12). Based on the toxicity risk score, 21% (n = 8), 54% (n = 21), and 26% (n = 10) were at low, intermediate, and high risk. 70% (n = 28) of patients had G ≥ 2 toxicities and 20% (n = 8) G ≥ 3 toxicities. G 2 and 3 diarrhea occurred in 28% (n = 11) and 5% (n = 2) respectively. 5% (n = 2) were hospitalized due to treatment-related toxicity. No G ≥ 3 cardiac toxicities were observed. 23% of patients (n = 9) had treatment delays, and 43% (n = 17) required a lapatinib dose reduction. The mean toxicity risk score was higher in patients who required dose reductions (Student's t: p = 0.02). No statistically significant relationship was found between toxicity risk scores and the presence of G ≥ 3 treatment toxicity (logistic regression: OR = 3.08, 95% CI [0.54, 21.2], p = 0.22). Conclusions: Among older patients with MBC (79% at intermediate or high risk of G ≥ 3 cytotoxic CT toxicity), trastuzumab and lapatinib were well tolerated, with only 20% experiencing G3 toxicities. The toxicity risk score was not found to be significantly related with treatment toxicity, which may be explained by the very low incidence of G3 events. Patients with a low toxicity risk score were not likely to require a lapatinib dose reduction. Citation Format: O'Connor T, Soto-Perez-de-Celis E, Blanchard S, Chapman A, Kimmick G, Muss H, Luu T, Waisman JR, Li D, Mortimer J, Yuan Y, Somlo G, Stewart D, Katheria V, Levi A, Hurria A. Tolerability of the combination of lapatinib and trastuzumab in older patients with HER2 positive metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-08.

Many cancer survivors experience menopausal symptoms, including female survivors taking aromatase inhibitors or with a history of oophorectomy or chemotherapy, and male survivors who received or are receiving androgen-ablative therapies. Sexual dysfunction is also common in cancer survivors. Sexual dysfunction and menopause-related symptoms can increase distress and have a significant negative impact on quality of life. This portion of the NCCN Guidelines for Survivorship provide recommendations for screening, evaluation, and treatment of sexual dysfunction and menopausal symptoms to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period.

OBJECTIVEGamma Knife radiosurgery (GKRS) is used to treat brain metastases from breast cancer (BMB) as the sole treatment or in conjunction with tumor resection and/or whole brain radiotherapy (WBRT). This study evaluates outcomes in BMB based on treatment techniques and tumor biological features.METHODSThe authors reviewed all patients treated with BMB between 2004 and 2014. Patients were identified from a prospectively collected radiosurgery database and institutional tumor registry; 214 patients were identified. Data were collected from aforementioned sources and supplemented with chart review where needed. Independent radiological review was performed for all available brain imaging in those treated with GKRS. Survival analyses are reported using Kaplan-Meier estimates.RESULTSDuring the 10-year study period, 214 patients with BMB were treated; 23% underwent GKRS alone, 46% underwent a combination of GKRS and WBRT, and 31% underwent WBRT alone. Median survival after diagnosis of BMB in those treated with GKRS alone was 21 months, and in those who received WBRT alone it was 3 months. In those treated with GKRS plus WBRT, no significant difference in median survival was observed between those receiving WBRT upfront or in a salvage setting following GKRS (19 months vs 14 months, p = 0.63). The median survival of patients with total metastatic tumor volume of ≤ 7 cm3 versus > 7 cm3 was 20 months vs 7 months (p < 0.001). Human epidermal growth factor receptor-2 (Her-2) positively impacted survival after diagnosis of BMB (19 months vs 12 months, p = 0.03). Estrogen receptor status did not influence survival after diagnosis of BMB. No difference was observed in survival after diagnosis of BMB based on receptor status in those who received WBRT alone.CONCLUSIONSIn this single-institution series of BMB, the addition of WBRT to GKRS did not significantly influence survival, nor did the number of lesions treated with GKRS. Survival after the diagnosis of BMB was most strongly affected by Her-2 positivity and total metastatic tumor volume.

Background: Physical resilience, the ability to resist decline and maintain functional status despite a stressor such as chemotherapy, is a central aspect of successful aging. Understanding clinical and biological factors associated with resilience in older women receiving chemotherapy for early breast cancer may facilitate the development of targeted interventions to maintain an individual’s robustness.Methods: Women age ≥65 (N=406) with Stage I-III breast cancer who were part of a clinical study of neo/adjuvant chemotherapy in older women were recruited from 16 sites (NCT01472094, R01AG037037). The Deficit Accumulation Index (DAI), a continuous score (0-1) calculated based on 51-items from geriatric assessment data (Cohen et al Cancer 2017), was measured before and after receipt of chemotherapy. DAI was categorized as robust (0.0 12 weeks, and 74% received primary prophylaxis with WBC growth factors. Among these 324 robust older women, 253 (78%) remained robust (resilient) at the end of chemotherapy, 63 (19%) became prefrail, and 8 (3%) became frail. In univariate analyses, patients treated with anthracycline (OR=0.63, p=0.09), planned duration of treatment > 12 weeks (OR=0.56, p=0.04), elevated IL-6 ≥2.7 pg/ml (OR=0.59, p=0.05), elevated CRP ≥4.3 μg/ml (OR=0.57, p=0.04), elevated D-dimer ≥0.7 μg/ml (OR=0.61, p=0.07), or at least one elevated biomarker (OR=0.18, p Conclusions: In this cohort of older women with early breast cancer who were robust prior to initiation of chemotherapy, 22% became prefrail or frail at end of treatment. Resilience to chemotherapy was related to inflammatory and coagulation biomarkers. Further research is needed to examine the mechanism underlying why some older women are resilient and retain their robustness after receiving treatment, whereas others experience decline, and further explore the role of inflammation/coagulation in this phenomenon. Table 1. Multivariable associations between baseline blood biomarkers and resilienceResilient (n=253) No. %Non-resilient (n=71) No. %Multivariable OR (95%CI)P value# of elevated biomarkers*064 (25)4 (6)1.00190 (36)29 (41)0.16 (0.05-0.55)0.004255 (22)22 (31)0.14 (0.04-0.49)0.002344 (17)16 (23)0.14 (0.04-0.51)0.003No elevated biomarker64 (25)4 (6)1.00At least one elevated189 (75)67 (94)0.15 (0.04-0.49)0.002*Biomarkers were defined as elevated using the entire cohort median value as cut off points (IL-6 ≥2.7 pg/ml, CRP ≥4.3 μg/ml, and D-dimer ≥0.7 μg/ml). Combined effects of biomarkers were examined by creating a four-level categorical combination variable: 0=all three biomarkers are Citation Format: Mina S Sedrak, Canlan Sun, Hyman Muss, Rachel A. Freedman, Allison Magnuson, Cary P. Gross, William P. Tew, Heidi D. Klepin, Tanya M. Wildes, Efrat Dotan, Tracey O'Connor, Mary Ann Fenton, Ruby Sharma, Andrew Chapman, Cynthia Owusu, Selina Chow, Heeyoung Kim, Vani Katheria, Mark LaBarge, William Dale, Saro Armenian, Susan Neuhausen, Harvey J. Cohen. Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-03.

12082 Background: Treating patients with metastatic cancer (MCA) requires timely integration of palliative and hospice care (PHC). The Surprise Question (SQ-“Would you be surprised if your patient died in the next year?”) may help predict short-term mortality in patients with chronic disease and prompt initiation of PHC. There limited data on the utility of the SQ in oncology and none controlling for age and cancer site (CS). This study evaluates the SQ in MCA. Methods: SQ data were collected using a clinical oncology pathway program (COP) in which the treating oncologist is required to answer the SQ for all patients with MCA. The cohort includes MCA patients with SQ entries from 5-1-2018 to 4-30-2019 providing cohorts with 6- and 12-months follow-up (f/u) from the date of the SQ. Vital status was determined as of 1-15-20. Over 90% of deaths are reported with 3 months of death. Models using SQ response (yes/no), cancer site and age were tested with logistic regression (LR) with Akaike Information Criterion (AIC) for model selection (lower number best model) and ANOVA to assess the value of the SQ in predicting mortality. Results: There were 655 and 1276 patients with MCA in COP with 1 year and 6 months f/u from the SQ, respectively. The proportion with the SQ response “No” (shorter expected survival) varied by cancer site (range 19% – 82% - e.g. breast 42%; pancreas 81%). The SQ was the best predictor compared to cancer site and age for 6 and 12-month mortality (LR Model A – lowest AIC). The odds ratio of death at one year from SQ-No vs. SQ-Yes was 3.8 (95% CI 2.7, 5.4) with a strong association between SQ response and 1-year and 6-month mortality (p < 0.001). See Table. Conclusions: Oncologist assessment of survival expectancy by the SQ in MCA is a strong predictor of mortality beyond cancer site and age. The treating oncologist’s response to SQ can serve as a simple and reliable predictive tool to identify those with MCA likely to die sooner who may benefit from timely referral to PHC. [Table: see text]

Background: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at increased risk for toxicity and dose reductions, often leading to decreased relative dose intensity (dRDI < 85%) and potentially compromised chemotherapy benefits. Identifying which older patients are projected to have dRDI with standard regimens could help to optimize systemic treatment delivery and completion. Methods: We prospectively enrolled patients aged ≥ 65 who were starting neo/adjuvant chemotherapy for HER2-negative, stage I-III breast cancer. Geriatric assessment and clinical variables were captured at baseline. Chemotherapy regimen, dosing, and treatment-related modifications (reductions, delays, discontinuation) were also captured. RDI was calculated as the ratio of actual dose delivered to intended dose. Our primary outcome was dRDI, which we defined as RDI < 85% (associated with poorer survival, Bonadonna et al. NEJM 1995). Bivariate logistic regression for dRDI was performed to elucidate the relationship with baseline factors. Stepwise regression was used to identify the significant factors that are independently associated with dRDI. Results: Of 323 patients (median age 69, range 65-86), 216 had HR+/HER2- breast cancer and 107 had triple negative breast cancer (TNBC). Patients were treated with taxotere and cyclophosphamide [TC] (47%), anthracycline-based regimens (46%), and cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] (7%). Overall, the mean RDI was 90.1% (median 100%, range 16.7%-100%), and 69 patients (21%) had dRDI (i.e. RDI 70, higher stage (II/III), use of non-TC regimens (anthracycline-based or CMF), abnormal liver function, KPS < 90, poor physical function, lack of social support, and cardiac conditions were associated with reduced RDI. Multivariate stepwise regression identified that anthracycline-based or CMF regimens (28% dRDI, OR=3.34, 95% CI 1.77-6.29), age >70 (27% dRDI, OR = 2.01, 95% CI 1.11-3.63), abnormal liver function (41% dRDI, OR = 2.50, 95% CI 1.10-5.66), and KPS < 90 (48% dRDI, OR = 4.31, 95% CI 2.06-9.03) were significantly associated with dRDI. dRDI was significantly associated with grade 3 or higher toxicities, hospitalization, dose reduction, dose delay, and early discontinuation of chemotherapy (all p < 0.001). Conclusion: Among older patients receiving neo/adjuvant chemotherapy for HER2-negative early-stage breast cancer, those aged > 70, treated with anthracycline or CMF regimens, with abnormal liver functions, and KPS < 90 were at substantially higher risk for reduced RDI (actual/planned dose) likely due to increased rates of toxicities, hospitalizations, dose modifications, and/or early treatment discontinuation. Future targeted supportive care interventions and/or alternative treatment regimens are needed to improve the delivery of chemotherapy in older patients who are predicted to have dRDI and better understand whether dRDI impacts outcomes in this population. Citation Format: Mina S Sedrak, Can-Lan Sun, Allison Magnuson, Hyman Muss, Rachel Freedman, Cary P Gross, William P Tew, Heidi Klepin, Tanya M Wildes, Efrat Dotan, Tracey O'Connor, Harvey J Cohen, Heeyoung Kim, Vani Katheria, Reena Jayani, Anait Arsenyan, Abrahm Levi, Kemeberly Charles, Arti Hurria, William Dale. Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-10.

Purpose: Cancer care in high-income countries (HICs) is often coordinated at multidisciplinary conferences (MDCs). However, among disparities encountered by cancer care providers in low- and middle-income countries (LMICs) is lack of access to specialized expertise. Modern communication technologies offer opportunity for remote MDCs; reports of this are limited and have described logistical barriers. We explored this concept further. Methods: We reviewed the experience of a cancer center in Lagos, Nigeria, connecting with multidisciplinary expertise in the United States (US). Multidisciplinary consultations were reviewed, and descriptive data were generated. Participating providers were surveyed. Results: Over a two-year period, 27 cases were referred for multidisciplinary consultation. Of these, 21 (78%) were referred to Roswell Park Comprehensive Cancer Center in Buffalo, NY, and 6 (22%) were referred to other US institutions. All but one (26, 97%) were referred using email, while one case was discussed via videoconference. Reasons for consultation were uncertainty about management in 10 patients (37%), need for validation of treatment plans in 14 patients (52%) and unusual clinical scenarios in 3 patients (11%). Limitations included incomplete documentation of treatment recommendations (5, 18.5%) and unavailable diagnostics (7, 26%) or therapies (3, 11%). Time to receive final recommendations ranged from 1 to 14 days, with a median of 3 days. Survey respondents (8, 100%) agreed or strongly agreed that remote MDCs added value, and that email was an effective, low-barrier method for their organization, with some drawbacks noted. Conclusion: This early experience demonstrates feasibility of remote MDCs to benefit providers and patients in LMICs. Future directions include using more sophisticated software and organization to maximize the scalability and sustainability of this concept.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included.

Introduction Farming is an occupation that incurs high rates of occupational injuries and illness, including fatalities. Internationally, legislative approaches to improve agricultural occupational safety and health (OSH) practices have been inconsistent in achieving those objectives. Many alternative initiatives to influence agricultural OSH practices have been developed, frequently emphasising information provision. In Ireland, evaluation of information provision approaches, such as classroom-based learning, has found that this is ineffective for improving agricultural OSH practices. However, peer-based learning using communities of practice (COPs), such as Teagasc dairy farmer discussion groups, presents a promising context for agricultural OSH promotion in Ireland. Research has established the efficacy of farmer discussion groups for promoting adoption of novel technologies and production practices. Little research has been undertaken to assess whether they are effective for promoting agricultural OSH practices. This paper describes the extent to which Teagasc dairy discussion groups engage with agricultural OSH, and identifies the characteristics associated with agricultural OSH engagement. The results are evaluated with respect to the existing literature regarding effective social learning for farming and OSH promotion, to assess the suitability of these COPs for agricultural OSH promotion. Methods Information about discussion group characteristics and engagement with OSH topics was collected using a survey of Teagasc dairy discussion group members, and a survey of Teagasc dairy discussion group facilitators. The statistical software R was used to assess variation in discussion group engagement with OSH, and the group characteristics statistically associated with that variation. Result Analysis of the results is ongoing and will be completed in September 2017. Discussion The findings of this study, including the evaluation framework developed from literature review, can contribute to effective agricultural OSH promotion in Ireland, and internationally. This is especially true for other countries with existing farmer COPs, such as farmer discussion groups in New Zealand and Wales.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment. This portion of the guidelines describes recommendations regarding screening for the effects of cancer and its treatment. The panel created a sample screening tool, specifically for use in combination with the NCCN Guidelines for Survivorship, to guide providers to topics that require more in-depth assessment. Effective screening and assessment can help providers deliver necessary and comprehensive survivorship care.

Healthy lifestyle habits have been associated with improved health outcomes and quality of life and, for some cancers, a reduced risk of recurrence and death. The NCCN Guidelines for Survivorship therefore recommend that cancer survivors be encouraged to achieve and maintain a healthy lifestyle, with attention to weight management, physical activity, and dietary habits. This section of the NCCN Guidelines focuses on recommendations regarding physical activity in survivors, including assessment for the risk of exercise-induced adverse events, exercise prescriptions, guidance for resistance training, and considerations for specific populations (eg, survivors with lymphedema, ostomies, peripheral neuropathy). In addition, strategies to encourage health behavioral change in survivors are discussed.

Many cancer survivors report that fatigue is a disruptive symptom even after treatment ends. Persistent cancer-related fatigue affects quality of life, because individuals become too tired to fully participate in the roles and activities that make life meaningful. Identification and management of fatigue remains an unmet need for many cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and management recommendations for fatigue in survivors. Management includes education and counseling, physical activity, psychosocial interventions, and pharmacologic treatments.

Sleep disorders, including insomnia and excessive sleepiness, affect a significant proportion of patients with cancer and survivors, often in combination with fatigue, anxiety, and depression. Improvements in sleep lead to improvements in fatigue, mood, and quality of life. This section of the NCCN Guidelines for Survivorship provides screening, diagnosis, and management recommendations for sleep disorders in survivors. Management includes combinations of sleep hygiene education, physical activity, psychosocial interventions, and pharmacologic treatments.

Many posttreatment cancer survivors experience chronic pain, often leading to psychological distress; decreased activity, motivation, and personal interactions; and an overall poor quality of life. This section of the NCCN Guidelines for Survivorship provides screening and management recommendations for pain in survivors. A multidisciplinary approach is recommended, with a combination of pharmacologic treatments, psychosocial and behavioral interventions, physical therapy and exercise, and interventional procedures.

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.