bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between symptom burden and perceived comorbidity in outpatients with common solid tumors.
Authors: Ritchie Christine , Manola Judith , Kvale Elizabeth , Snyder Claire Frances , Fisch Michael 
Published: March 2020

6080 Background: Cancer patients have high symptom burden, but it is unclear whether comorbid conditions are associated with patient-reported symptom burden (the number and severity of symptoms). Methods: The Eastern Cooperative Oncology Group (ECOG) enrolled 3106 patients with invasive cancer of the breast, colon/rectum, prostate and lung, regardless of phase of care or stage of disease. At baseline, patients completed the M.D. Anderson Symptom Inventory (MDASI) and were also asked how bothered they were by difficulties related to health problems other than cancer. Symptom burden (SB) was defined as the number of symptoms scored 7 or higher on the 13-item MDASI physical scale. Variance-weighted least squares regression was used to identify factors associated with increasing levels of being bothered by comorbid conditions. Results: About 65% of patients were at least a little bothered by symptoms associated with comorbidities. There was a strong association between increased bother by comorbidities and increased SB (p<0.0001). Among those not bothered by difficulties related to comorbidities, ≥1 symptom was rated 7 or worse by 29% of patients, compared to 51% in patients bothered by difficulties related to comorbidities (Fisher’s exact p<0.0001). Except for hair loss, the severity of all symptoms was higher in those patients reporting bother due to other perceived comorbidities. Factors associated with increased bother include SB (p<0.0001), taking medications for diabetes (p<0.0001), impaired ECOG performance status (p=0.03), older age (p=0.004), and being perceived by the clinician as having higher degree of difficulty for providing care (p<0.0001). Conclusions: Symptom burden varies significantly according to the degree to which cancer patients perceive bother that they attribute to comorbid health problems. Perception of comorbidity is worth exploring as a stratification factor in symptom research and as an indicator for complexity in patient care.
The impact of race/ethnicity concordance between patients and their navigators in time to diagnostic resolution of breast and cervical cancer screening abnormalities.
Authors: Charlot Marjory , Santana M. Christina , Chen Clara A , Palmisano Joseph N , Bak Sharon , Heeren Timothy C , Battaglia Tracy Ann , Freund Karen M 
Published: March 2020

6097 Background: Patient navigators have been shown to reduce cancer disparities among racial/ethnic minorities by improving timely diagnosis and treatment of cancer. For a group of navigators who received cultural competency training, we sought to determine if racial/ ethnic concordance of the navigator and patient improved time to diagnostic resolution of cancer screening abnormalities. Methods: Demographic data on 1466 patients and their 23 navigators from the Boston Patient Navigation Research Program were used to assess concordance by race and ethnicity. All participants with either breast (n=751) or cervical (n=715) screening abnormalities were followed up to one year. Kaplan-Meier survival curves and proportional hazards regression models examined the effect of race/ethnicity concordance on time to definitive diagnosis, adjusting for age, race, language, economic status, insurance status, and severity of screening abnormality. Analyses were performed separately for the breast and cervical groups. Results: Of the 1466 patients, 32% were White, 27% Black, 31% Hispanic, and 10% Asian. Navigators were 61% White, 17% Black, 13% Hispanic and 9% Asian. Fifty eight percent of patient-navigator pairs were concordant by race/ethnicity. Overall rate of diagnostic resolution of cancer screening abnormalities within 365 days was high at 90%. In both the breast and cervical cancer screening groups, racial/ethnic concordance was not associated with time to diagnostic resolution, with an aHR 1.03 (95% CI: 0.85, 1.25) for breast patients and HR 1.02 (95% CI: 0.85, 1.21) for cervical patients. Conclusions: Patient-navigator racial/ethnic concordance is not associated with time to diagnostic resolution of cancer screening abnormalities, in part because overall rates of diagnostic resolution were high. Our data suggest that with cultural competency training, navigators can be equally effective with patients from different ethnic and cultural backgrounds.
Assessment of cancer registries (CR) in low- and middle-income countries (LMCs).
Authors: Zullig Leah L. , Vanderburg Sky , Johnson Doug , Oneko Olola , Muiruri Charles , Ntabaye Moshi , Abernethy Amy Pickar , Bartlett John , Zafar Yousuf 
Published: March 2020

6102 Background: CRs are crucial for cancer control, yet few global standards exist. This study identifies characteristics of quality CRs in LMCs and globally. Methods: A Medline search was conducted in PubMed to identify peer-reviewed articles describing: 1) CR development and functionality 2) types of CRs and 3) implementation, development and utility of CRs in LMCs. We examined articles describing CRs and assessed benchmarking data that could be used to define quality characteristics. Full-text, English-language articles were reviewed. References cited were searched for additional articles. We categorized characteristics into 4 domains: comparability, completeness, validity and timeliness. Results: The literature search yielded 16 key characteristics within 4 domains that may define high quality CRs. In the “comparability” domain, the key characteristic was use of standard definitions. CRs in the US, Europe and China generally adhere to the International Classification of Diseases for Oncology and histological verification of disease; in 2007 only 40% of African registries did so. In the “completeness” domain the key characteristic was population coverage. African CRs monitor 8% of the population, the Costa Rican registry covers 90%, US and Madras cancer registries reach 96%. In the “validity” domain the key criterion was pathologic diagnosis confirmation. Most LMC CRs are not pathology-based. CRs in wealthier settings like Hong Kong report histologic confirmation in >85% of cases. In the “timeliness” domain standards for timely data reporting are largely undocumented. Conclusions: No consensus exists on characteristics of quality CRs in a global context. The current study provides an initial set of metrics. A Delphi panel of international experts is planned to further address this. Based on this literature review, CRs in LMCs have limited reporting, validation and regional population coverage.
Chemotherapy associated myelosuppression and disease-free and overall survival: A systematic review and evidence summary.
Authors: Poniewierski Marek S. , Wogu Adane , Culakova Eva , Rosen Alexander , Kuderer Nicole Maria , Crawford Jeffrey , Dale David C. , Lyman Gary H. 
Published: March 2020

6129 Background: Myelosuppression remains the major dose-limiting toxicity of cancer chemotherapy. The risk of myelotoxicity is associated with the specific drugs, doses and schedule utilized along with patient differences in drug metabolism and tolerance. Several retrospective studies have suggested that patients surviving early myelosuppression may experience improved disease-free and overall survival. Methods: A literature search was conducted of studies published between 1980 - 2011 reporting a relationship between chemotherapy-associated myelosuppression and cancer recurrence and/or mortality. Eligibility was restricted to adult cancer patients receiving chemotherapy and reporting disease recurrence or mortality in relationship to myelosuppression. Dual blinded study identification and data extraction were employed. Hazard ratio (HR) estimates for clinical outcomes were based on random effects models. Results: A total of 1,896 studies were identified in the initial search. A total of 25 studies analyzing results in 14,029 (range 23 – 4,626) patients were deemed to be eligible. Studies included cancers of the breast (7), lung (8), ovary (3), gastrointestinal (5), and Hodgkin lymphoma (2). Overall, neutropenia was observed in 7,577 (54%) patients. Overall survival was reported in 17 studies, recurrence or progression free survival in 11, and both in 5. Outcomes were based on HRs in 16, median survival in 14 and neither in 2. The HRs for survival and progression/recurrence free survival with and without myelosuppression were 0.66 [95%CI: 0.56-0.78; P<.001] and 0.72 [95%CI: 0.60-0.87; P<.001], respectively. There was no difference in estimated HRs in studies employing landmark analysis. Conclusions: Myelosuppression appears to be associated with lower risk of recurrence and death across cancer types and settings. These data do not distinguish between the effects of chemotherapy dose intensity versus patient variation drug metabolism resulting in greater efficacy and toxicity in some patients. Nevertheless, these results suggest that reducing chemotherapy dose intensity to avoid myelosuppression may not be a prudent strategy even in patients with advanced disease.
Relationship between whole-body tumor burden and quality of life in patients with neurofibromatosis.
Authors: Plotkin Scott Randall , Merker Vanessa L. , Bredella Miriam A. , Cai Wenli , Kassarjian Ara , Harris Gordon J , Muzikansky Alona , Askenazi Manor , Nguyen Rosa , Wenzel Ralph , Mautner Victor-Felix 
Published: March 2020

6136 Background: NF1, NF2, and schwannomatosis are a group of related genetic disorders in which affected individuals share the predisposition to develop multiple nerve sheath tumors. While previous studies have investigated the relationship between cutaneous tumor burden and quality of life, the relation between internal tumors and quality of life is unknown. Methods: As part of an IRB-approved research study, we performed whole-body MRI and administered the short form (SF)-36 to 245 adult subjects with NF. The number and location of internal nerve sheath tumors in each patient was identified by a board-certified radiologist and tumor volume was calculated using semi-automated volumetric analysis. One sample t-tests were used to compare subjects’ SF-36 scores to general population means. Independent linear regression analyses controlling for age and gender effects were used to relate whole-body tumor count, volume, and distribution (via Gini coefficient) to each domain of the SF-36. Results: 245 patients (142 with NF1, 53 with NF2, 50 with schwannomatosis) completed the study. On the SF-36, subjects with NF1 showed reduced quality of life in the physical role, emotional role, and mental health domains compared to the normal population (p<0.05). Subjects with NF2 showed reductions in the physical functioning, physical role, general health, and social functioning domains while subjects with schwannomatosis showed reductions in the physical role and bodily pain domains (p<0.05). In linear regression analysis, increased tumor number, increased tumor volume, and decreased Gini coefficient were correlated with decreased physical functioning in patients with NF2 (p<0.01). There was also a trend for increasing tumor volume to be correlated with decreased physical role and increased bodily pain in patients with NF1 and with increased bodily pain in patients with schwannomatosis (p<0.10). Conclusions: In our multi-institutional cohort, patients with all forms of neurofibromatosis show selected deficits in quality of life. Internal tumor burden does not correlate with these deficits, with the exception of physical function in NF2 patients.
Predictive factors on the receipt and completion of adjuvant chemotherapy in a mixed sociodemographic cohort of patients.
Authors: Polite Blase N. , Smith David M , Cipriano Toni 
Published: March 2020

6137 Background: African Americans are more likely to die from breast, colon and lung cancer compared to whites. They are also less likely to receive and complete recommended therapy. The reasons for this are unknown. Methods: Breast, colon, and lung cancer patients eligible for adjuvant chemotherapy (stage IB-III breast, stage IIB-III colon, and Stage IB, II lung) and who received surgery at 2 urban medical centers, were approached between 2008 and 2010 and completed a self-administered survey focusing on sociodemographic factors, including social support, anxiety, depression, co-morbidities, trust and God Locus of Control (e.g., Whatever happens to my cancer is God’s will). These variables were related to receipt and completion of chemotherapy. 191 patients were approached, 161 consented and 30 refused (16%); out of the 161, 23 were deemed ineligible because of previous cancers, non-curative stage or receipt of chemotherapy in the neoadjuvant setting. Results: Final sample consisted of 138 pts. Median age: 54; sex:81% F; Race/Ethnicity:47% AA, 38% white, 9% Hispanic, 6% Asian/PI; Cancer Type: 73% Breast, 21% Colon, 6% Lung. Compared to whites, AA were more likely to have incomes<20K (35% vs. 10%, p=.0002), have any comorbidities (80% vs. 57%, p=0.006), and have high levels of God Locus of Control (56% vs 27%, p=0.003). There were no differences by race in chemotherapy receipt (89% vs. 88%) or relative dose intensity (RDI) of chemo>=85% (58% vs. 67%). No factor in our model predicted chemotherapy receipt or RDI at a significant level. Pts with high God Locus of Control were somewhat more likely to start chemotherapy (OR 1.7, p=0.25) but were less likely to complete therapy (OR 0.55, p=0.19). The magnitude of these relationships held after controlling for age, race, comorbidities, cancer type, functional status, and social support. Conclusions: In a mixed sociodemographic cohort of patients, receipt and completion of adjuvant chemotherapy was similar by measured sociodemographic variables. Only high God Locus of Control was suggestive of being less likely to complete chemotherapy. Further attention and research on the role of religious beliefs in the cancer decision making process is warranted.
Susceptibility of HER2+ breast cancer cells to poly (ADP-ribose) polymerase (PARP) inhibition independent of an inherent DNA repair defect.
Authors: Yang Eddy Shih-Hsin , Nowsheen Somaira , Cooper Tiffiny , LoBuglio Albert F. , Bonner James A. 
Published: March 2020

621 Background: HER2 overexpression in breast cancer confers increased tumor aggressiveness. Targeted therapy against HER2 has improved outcomes, but resistance and disease progression ultimately occurs, thus necessitating novel therapeutic strategies. PARP inhibitors target homologous recombination (HR) deficient tumors, such as the BRCA-associated breast and ovarian cancers. In this study, we report unexpected susceptibility of HER2+ breast cancer cells to PARP inhibition alone independent of an inherent HR deficiency. Methods: Cell viability was measured using colony formation and ATPLite assays. Tumor growth delay was assessed in vivo in mice bearing breast cancer xenografts. Proteins were detected by immunoblotting. HR was assayed using radiation (IR)-induced Rad51 foci or a GFP-based HR assay. NFκB activity was measured using a NFκB-driven luciferase assay. Results: Surprisingly, PARP inhibition with ABT-888 alone reduced the colony forming ability and cell viability of the HER2+ breast cancer cell lines BT474, SKBR3, MDA-MB361, and HCC1954 (~70 – 99% reduction at 10μM). This susceptibility did not correlate with an inherent HR deficit. Interestingly, HER2 overexpression itself may be one mechanism of susceptibility to ABT-888 as evidenced by increased cellular cytotoxicity and in vivo tumor growth delay of MCF7 cells stably expressing HER2. Further dissection of the mechanism revealed that NFκB transcriptional activity was significantly inhibited by ABT-888 (>95%) which corresponded with reduced levels of phosphorylated p65 and total IKKα, and a concomitant increase in IkBα. Furthermore, overexpression of p65 abrogated cellular sensitivity to ABT-888. Conclusions: HER2+ breast cancer cells are highly susceptible to PARP inhibition despite being HR proficient. This may be, in part, due to inhibition of NFκB. Further investigation of whether the addition of PARP inhibition to HER2 targeted therapy will delay the onset of resistance to therapy is warranted to potentially improve outcomes in HER2+ breast cancer patients.
ADAM17 as a novel therapeutic target for HER2-positive breast cancer.
Authors: Sukor Sumainizah , McGowan Patricia M. , Mullooly Maeve , Pierce Aisling , Crown John , O'Donovan Norma , Duffy Michael J. 
Published: March 2020

622 Background: Although the HER2 gene is amplifiend/overexpressed in 15-20% of breast cancers, only a proportion of these patients benefit from anti-HER2 therapy. Clearly additional biomarkers and/or therapeutic targets are necessary to enhance efficacy and improve outcome in these patients. Here, we tested the hypothesis that inhibition of ADAM17-mediated release of HER ligands may enhance response to trastuzumab and lapatinib. Methods: The ADAM17-selective inhibitor, PF-5480090 (Pfizer) both alone and in combination with lapatinib, trastuzumab or 5FU was tested for potential growth inhibitory effects on a panel of 4 HER2-positive breast cancer cell lines (BT474, MDA-MB-453, SKBR3 and JIMT-1). Results: Using the MTT viability assay, treatment with 1 µM TMI-2 resulted in a significant reduction in cell proliferation compared to vehicle control in BT474 (p=0.01), MDA-MB-453 (p < 0.005), JIMT-1 (p=0.002) and SKBR3 cells (p < 0.005). Addition of PF-5480090 to lapatinib resulted in a significant reduction in cell growth compared to lapatinib alone (JIMT-1: p < 0.005; SKBR3: p < 0.005; MDA-MB-453: p < 0.005), while addition of PF-5480090 to trastuzumab resulted in significant reduction in cell growth compared to trastuzumab alone (JIMT-1: p < 0.005; SKBR3: p < 0.005; MDA-MB-453: p=0.001). Addition of PF-5480090 to 5FU resulted in significant reduction in growth compared to 5FU alone (JIMT-1: p < 0.005; SKBR3: p < 0.005; MDA-MB-453: p=0.001). Consistent with its ability to block proliferation, addition of PF-5480090 significantly reduced release of TGFalpha (BT474: p=0.003; JIMT1: p=0.023; SKBR3: p=0.036 and MDA-MB-453: p=0.014). Conclusions: Inhibitionof ADAM17 resulted in growth inhibitory responses in HER2-positive breast cancer cell lines. Furthermore, addition of PF-5480090 to lapatinib, trastuzumab or 5FU resulted in significant growth inhibition compared to these agents alone. We propose that inhibition of ADAM17 may be used in combination with existing treatments for HER2-positive breast cancer. Acknowledgement. The authors thank SFI (SRC award, 08/SRC/B1410 to MTCI) for funding this work.
HER2 assessment and Ki-67 labeling index in a cohort of male breast cases: The Ich Network on Cancer Research (INCaRe) experience.
Authors: Masci Giovanna , Caruso Michele , Losurdo Agnese , Salvini Piermario , Carnaghi Carlo , Di Tommaso Luca , Zuradelli Monica , Manuguerra Giovanna , Rota Selene , Aiello Rosa Anna , Gullo Giuseppe , Torrisi Rosalba , Beretta Giordano D. , Santoro Armando 
Published: March 2020

623 Background: The overall incidence of male breast cancers (MBC) is around 1% of all breast cancers and is on the rise.Most of our current knowledge regarding its biology and treatment strategies has been extrapolated from its female counterpart. However, from literature data, it is more and more evident that MBC has biological differences compared with female breast cancer (FBC). While hormone receptors are more frequently positive in MBC than in FBC, HER-2 seems to be less expressed in MBC than in FBC, with data ranging from 0 to 18%; no data on Ki-67 have been so far reported. Methods: We retrospectively analyzed the immunohistochemical expression of hormone receptors status, HER-2 protein expression, and Ki-67 in 76 consecutive MBCs, treated within the Humanitas Institutes Network on Cancer Research (INCaRe). HER-2 determinations were carried out according to ASCO/ACP and NEQAS guidelines: cases with score 2+ at IHC were further examined by fluorescent in situ hybridation (FISH). Results: From 2000 to 2011, we treated 76 male breast cases (age 25-87, median 64): 72 patients (94%) had ductal carcinoma and 4 had rare histotypes (2 papillary, 1 mucinous and 1 cribryform). Thirthy-two of 76 patients (42%) had positive axillary lymph-nodes, while 6 (8%) were metastatic at diagnosis. Of these, estrogen receptor and progesterone receptor were positive in 96% and 93% patients respectively; HER-2, evaluable in 67 patients, was positive in 11 (16%). Ki-67 was evaluable in 75 patients and was > 20% in 24 cases (32%), with 20/24 (26%) with Ki-67 > 30%. Grading was evaluable in 65 patients: G1 in 2 (3%), G2 in 41(63%) and G3 in 22 (34%), respectively. Conclusions: In these series, MBC show different patterns from FBC, with some favorable aspects such as higher hormone receptor status and much lower HER-2 expression and some unfavorable features, such as higher Ki-67 values. Although further studies are needed to confirm these data, different treatment strategies would be suggested in MBC than its female counterpart.
Efficacy of INK128, an mTORC1/mTORC2 kinase inhibitor, in breast cancer models driven by HER2-PI3K-AKT-mTOR pathway.
Authors: De Pradip , Sun Yuliang , Wu Hui , Rommel Christian , Liu Yi , Dey Nandini , Leyland-Jones Brian 
Published: March 2020

626 Background: Downstream of the PI3K-AKT pathway, the mTOR has been shown to be essential effector in promoting cell proliferation, survival, mRNA translation and tumor susceptibility. Aberrant activation of the PI3K-AKT-mTOR pathway occurs frequently in breast tumor (BT) and contributes to resistance to trastuzumab (T). Using a HER2 amplified BT model; we investigated the antitumor efficacy of the dual mTORC1/mTORC2 kinase inhibitor INK128 alone and in combination with T. Methods: The antiproliferative and HER2-mediated cellular signaling (pAKT, pP70S6K, pS6RP, p4EBP1 and p-ERK) effects of INK128 alone and in combination with T were evaluated in HER2 amplified T-sensitive (BT474), T-resistant (BT474HR), and HER2 amplified/PIK3CA mutated (HCC1954, UACC893) BT cell lines by MTT assay and Western blots. Athymic mice bearing BT474 and BT474HR xenograft tumors were treated with INK128 and T (alone and in combination). Results: (1)INK128 exhibited excellent in vitro cell killing activity in MTT assay with IC50’s below 50nM. INK128 was more potent when combined with T, (2) INK128 blocked mTORC1, mTORC2 and thus did not cause the mTORC2 activation of AKT observed with rapalogues, (3) inhibition of phosphorylation of AKT(S473), P70S6K, S6RP, and 4EBP1(T37/46, T70) was observed following INK128 treatment, and the combination of INK128 and T more effectively blocked the PI3K-AKT-mTOR pathway, (4) INK128 dose-dependently blocked 3D-ON-TOP clonogenic growth of HER2+ cells. This effect was potentiated in the presence of T and (5) xenograft data show that the combination of INK128 and T has strongly enhanced anti-tumor effect in both sensitive and resistant models, something that cannot be achieved by either monotherapy. Conclusions: Our data suggest that 1) therapeutic targeting of the PI3K-AKT-mTOR signaling should be effective in abrogating resistance to T therapy in HER2+ BT, 2) INK128 mitigates the feedback activation of AKT caused by selective inhibition of mTORC1 and 3) targeting both the HER2 and the mTORC1/2 signaling pathways is an attractive strategy to enhance the clinical activity of T therapy, as well as to prevent or delay the development of resistance.