tbuckley/cabot-search huggingface dataset:
Heterogeneous prevalence of mutations in <i>KRAS</i>, <i>BRAF</i>, and <i>PIK3CA</i> genes among Sardinian patients with colorectal carcinoma.
Authors: G. Palomba, M. Colombino, A. S. Contu, B. Massidda, G. Baldino, M. T. Ionta, A. Pazzola, F. Capelli, V. Trova, T. Sedda, A. Farris, F. Tanda, M. Budroni, G. Palmieri, A. Cossu
Journal: Journal of Clinical Oncology (2011)

e14100 Background: In addition to KRAS mutations, it has been suggested that either BRAF or PIK3CA mutations might also confer tumor resistance to EGFR-targeted antibodies in colorectal cancer (CRC). However, conflicting data are being generated regarding the incidence of BRAF and PIK3CA mutations in different populations as well as the impact on response to such a therapy. Methods: From April 2009, formalin-fixed paraffin-embedded tissues (N=381) were prospectively collected from CRC patients at Sardinian clinics. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. Results: KRAS tumor mutation rate was 30% (114/381 positive cases), with no significant differences according to sex and diagnosis age. Among the 370 patients with ascertained Sardinian origin, 111 (30%) presented a mutated KRAS gene; however, distribution of positive cases was different across the island (63/162 [39%] in North Sardinia vs. 48/208 [23%] in Middle-South Sardinia). Since this is consistent with the discrepancy in distribution of germline mutations for other malignancies (breast cancer and melanoma, as we previously described) within Sardinian population, one could speculate that a different genetic background may influence the frequency of KRAS somatic mutations. Among 324 CRC cases analyzed to date, no mutation in BRAF gene was surprisingly observed. Conversely, PIK3CA was found mutated in 152/351 (43%) patients, again with no significant differences according to sex and age. For this gene, no significant difference in mutation prevalence was observed within Sardinian population (71 [48%] in 149 cases from northern vs. 81 [42%] in 192 cases from central-southern island). Role of PIK3CA mutations in predicting response to anti-EGFR antibodies in patients with wild-type KRAS is being evaluated. Conclusions: These findings further support the hypothesis that patients’ origin and genetic background may contribute to determine the incidence rate of somatic mutations in cancer genes.
RAD51 and brain metastases (BM) in patients (pts) with HER2+ breast cancer.
Authors: R. Duchnowska, J. Jassem, E. Szutowicz, W. Biernat, T. Jankowski, W. Och, R. Staszkiewicz, M. Chudzik, W. Rogowski, N. Flores, S. Woditschka, L. Li, C. Goswami, M. A. Thorat, Y. Gokmen-Polar, G. W. Sledge, P. S. Steeg, D. Palmieri, S. S. Badve
Journal: Journal of Clinical Oncology (2011)

634 Background: BM is a common occurrence in HER2-positive breast cancer pts. If the pts most likely to develop BM could be identified, prophylactic strategies might prevent or delay occurrence of this failure. Our previous work focusing on clinical and pathological factors coupled with gene expression analysis identified a 13 gene signature that together could predict the likelihood brain metastases within the first 3 years (early vs. late occurrence) after diagnosis (J Clin Oncol 2008; 26: 45s). More specifically, it suggested that a number of proteins involved in DNA double strand break repair are overexpressed in untreated primary breast tumors from patients who developed BM within 3 years of diagnosis. Methods: To determine the impact of DNA repair genes in early breast tumorigenesis, a 3D culture model system of immortal, nontumorigenic human MCF10A breast cells was used, with and without ectopic expression of HER2 and the DNA repair genes BARD1 and RAD51 from the signature. The number and morphology of breast acini were scored using indirect immunofluorescence and confocal microscopy. Results: Overexpression of HER2 increased the proportion of acini showing invasion into the extracellular matrix by 4.2-fold (P=0.05). Overexpression of RAD51, with or without concomitant HER2 overexpression, more strongly promoted invasive growth, with increases of 6.5-fold and 6.8-fold, respectively, over control transfectants (P=0.03 and 0.004, respectively). BARD1 overexpression promoted invasive growth 2.5-fold over control transfectants (P=0.04) but did not exceed or interact with HER2 overexpression. Conclusions: These data indicate that RAD51 overexpression occurs early in carcinogenesis and that it may accelerate the invasion process. This may underlie the proclivity of patients with RAD51 overexpressing tumors to develop brain metastases.
Public reporting outcomes of multidisciplinary cancer care: Conceptual issues.
Authors: James Austin Talcott
Journal: Journal of Clinical Oncology (2012)

280 Background: Patient outcomes are the most valid measures of quality of care. Public reporting makes them available to patients, referring physicians and payers. Our institution has committed to reporting all cancer patient outcomes. In carrying out that objective, we encountered novel analytical issues arising from differences between the usually reported treatments, surgical procedures, and multidisciplinary cancer care. We present important conceptual issues we identified. Methods: Analytic description of methodological issues encountered in publishing cancer patient outcomes. Results: Issues include: (1) Assigning responsibility. Patient outcomes of multidisciplinary cancer care can be influenced by multiple oncology specialties and institutions. While providers directly control only the treatment they provide, providers share collective responsibility for executing the treatment plan, coordinating care and vouching for the quality of collaborating providers. Therefore, reporting outcomes of one element of multidisciplinary care is incomplete and inadequate. (2) Claiming responsibility. Providers with institutional affiliations but no involvement in quality improvement or reporting processes should be excluded from public reporting. Minimum requirements to qualify for public institutional affiliation should be enforced and “free riders” identified. (3) Defining and presenting valid comparison populations. Treatment trials’ eligibility criteria and recruitment practices exclude poorer prognosis patients, producing biased comparisons to complete “registry” populations that distort patient expectations. Publishing outcomes of well-characterized subpopulations improves valid results and provides more individualized information. Conclusions: Reporting patient outcomes after multidisciplinary cancer care raises novel conceptual issues. We discuss our response to three important issues.
Quality of life (QoL) in patients (pts) with squamous (SCC) NSCLC treated with <i>nab</i>-paclitaxel with carboplatin (<i>nab</i>-P/C) induction therapy: Interim analysis of the phase III ABOUND.sqm study.
Authors: Rogerio Lilenbaum, Corey J. Langer, Robert M. Jotte, Edward S. Kim, Amy Ko, Teng Jin Ong, Mark A. Socinski, Peter Staib, Nataliya Trunova, David R. Spigel
Journal: Journal of Clinical Oncology (2016)

64 Background: Recent data on QoL in pts with advanced NSCLC treated with platinum-doublets are limited. This interim analysis evaluated QoL in pts with SCC NSCLC treated with nab-P/C during the induction part of the ABOUND.sqm study. Methods: In the ongoing phase III ABOUND.sqm study, pts with advanced SCC NSCLC are treated with first-line nab-P 100 mg/m 2 d 1, 8, 15 and C AUC 6 mg•min/mL d 1 (21-d cycles) for 4 cycles (induction). Pts not progressing after 4 cycles are randomized 2:1 to maintenance nab-P 100 mg/m 2 d 1 and 8 of each 21-d cycle + best supportive care (BSC) or BSC alone until progression. The primary endpoint is PFS from randomization to maintenance. QoL, an exploratory endpoint, was assessed using predefined PRO instruments, LCSS and EQ-5D-5L, on d 1 of each cycle. As the study is ongoing, this pre-planned analysis included data for QoL that were reported up to the cutoff date. Results: Of 128 pts included in this interim analysis, &gt; 80% completed baseline (BL) + ≥ 1 post-BL PRO assessments. The median age was 68 years, 65% were male, and 99% had an ECOG PS of 0-1. Overall, the symptom burden index and average total score of the LCSS PRO were improved during induction therapy with nab-P/C; ≈ 50% of pts had clinically meaningful improvements (≥ 10 mm [VAS]) from BL in the composite LCSS items of cough, shortness of breath, and hemoptysis. More than 80% of pts maintained or improved each dimension of the EQ-5D-5L from BL, and a substantial proportion reported complete resolution of ≥ 1 specific dimension problem during induction (33%-48%; Table). No unusual safety signals were observed. Conclusions: This interim analysis demonstrates that QoL was maintained or improved in pts with SCC NSCLC during nab-P/C induction therapy. For pts who reported problems in EQ-5D-5L dimensions at BL, many achieved complete resolution at least once during chemotherapy. Clinical trial information: NCT02027428. [Table: see text]
Are there any molecular biologic factors which explain the poorer prognosis of elderly patients with advanced ovarian cancer?
Authors: R. Chekerov, E. I. Braicu, R. Richter, G. Oskay-Özcelik, K. Pietzner, C. Fotopoulou, B. W. Lisboa, W. Lichtenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2011)

e15549 Background: Studies indicates clearly a poorer survival for elderly patients with advanced ovarian cancer (AOC). It is unclear whether tumor biological factors or the clinical management is responsible for the poor outcome of elderly patients.In this prospective study we analysed the correlation of the age with other clinicopathological parameters and the expression of 7 commonly used biomarkers in patients with advanced ovarian cancer. Methods: Tumour samples were collected prospectively from 91selected women classified in five different age groups which undergone surgical interventions because of primary or recurrent commonly serous ovarian cancer. Clinical data included patient's age, FIGO-stage, histological grade, ascites and postoperative tumor residuals as relevant prognostic factors. For the immunohistochemistry a tissue microarray (TMA) was performed and the expression of Ki-67, HER-2/neu, Estrogenreceptor (ER), Progesteronreceptor (PR), p53, CA 125 and VEGFR1 was investigated. Results: The 5 groups selected patients younger than 35 years, 36 - 50 years, 51 - 65 years, 66 - 75 years and older than 76 years. No difference in survival was observed between the selected age groups. According to age no significant difference in the expression levels of the analysed biomarkers were evaluated, where HER-2 and PR showed commonly an negative expression, and a tendency of decrease of ER- and CA125-expression was registered in older patients. None of the investigated clinicopathological parameters and biomarkers correlated independently with survival in the overall study population. Conclusions: Patients with advanced ovarian cancer have a similar clinicopathological characteristics, biomarker expression status and postoperative survival.Based on these data quality of surgery and systemic therapy will influence mainly the outcome of elderly patients.
Long-term employment outcomes among partners of patients with early-stage breast cancer.
Authors: Christine Marie Veenstra, Lauren P. Wallner, Cathy Bradley, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2016)

12 Background: Undesired work loss comprises one of the many personal costs faced by cancer patients and their families. Multiple studies have described the long-term employment outcomes among patients with early-stage breast cancer, and show that a significant proportion of women face long-term job loss as a result of their cancer diagnosis and treatment. However, little is known about the employment outcomes of partners of breast cancer patients. Methods: Women with non-metastatic breast cancer identified by the Detroit and Los Angeles SEER registries between 6/05-2/07 were surveyed at 9 months (Time 1) and 4 years (Time 2) after diagnosis. Latina and black women were oversampled. Partners were surveyed at Time 2. We performed descriptive analyses of those partners who were not retired at the time they completed the survey. As part of a larger survey assessing the experiences of partners of breast cancer patients, partners were queried regarding the impact of the patient’s breast cancer diagnosis and treatment on their own employment and finances. Results: Of 774 eligible partners, 517 (67%) completed the survey. We included 280 non-retired partners in our analyses. 54% were white, 31% were Latino, and 10% were black. The majority of partners (86%) worked during the year following the patient’s diagnosis and 219 (90%) were working at the time of survey 4 years post-diagnosis. 50% of partners reported that work was a welcome source of support; 32% decreased their work hours as a result of the patient’s breast cancer. In order to maintain health insurance, 64% reported it was very/extremely important to keep their jobs and 51% reported it was very/extremely important to avoid changing jobs. 32% of partners reported their financial status was worse off because of the patient’s breast cancer; 20% were worse off regarding health insurance, and 19% were worse off regarding employment status. Conclusions: In contrast to breast cancer patients, most partners reported long-term job retention. Many partners kept working or avoided changing jobs in order to maintain health insurance. Nearly one-third of partners reported that their financial status was worse off because of the patient’s breast cancer diagnosis and treatment.
Does expected survival influence palliative radiotherapy treatment recommendations?
Authors: David L Ma, Brock J Debenham, Bronwen LeGuerrier, Kim Paulson, Sunita Ghosh, Fleur Huang, Karen P Chu, Diane Severin, John Amanie, Tirath Nijjar, Samir Patel, Jim Rose, Ericka Wiebe, Brita Lavender Danielson, Alysa Fairchild
Journal: Journal of Clinical Oncology (2015)

35 Background: Survival is often overestimated, yet physicians rely on such predictions to recommend appropriate therapy and assist with end-of-life planning. Administration of radiotherapy (RT) within the last 30 days of life has been suggested as an indicator of poor quality care, since acute side effects reduce quality of life with insufficient time for symptomatic benefit. We investigated whether life expectancy predicted at the time of consultation correlates with palliative RT recommendations. Methods: Radiation oncologists from a dedicated palliative Radiation Oncology outpatient clinic anonymously completed survival estimations after clinical assessment, and recorded factors upon which each estimate was based. Demographics, primary histology, RT details, and date of death were abstracted. Summary statistics and Kaplan-Meier estimates of actual survival (AS) were obtained. Correlations between AS and clinical predictions of survival (CPS) were calculated using Spearman’s correlation coefficient (r). Multivariate logistic regression analysis explored factors associated with RT recommendations. Results: 476 survival predictions were made for 420 unique patients (06/2010-01/2014). Median age was 67.7 years, 61.9% were male and 44.0% had lung cancer. Karnofsky Performance Status (KPS) was &gt; 70 at 23.9% of clinic visits. At 84.5% of consultations, RT was prescribed to 538 separate volumes (29.2% receiving 8Gy, 54.8% 20Gy, 6.3% 30Gy, 9.7% other). Mean AS was 179 days (SD 187d), moderately correlating with mean CPS of 242 days (SD 261d) with r = 0.38 (p &lt; 0.0001). Factors most frequently cited as influencing CPS were KPS and extent of disease. At the time of 30/476 visits, CPS was &lt; 30 days; at 19 of these visits, RT was prescribed to 26 volumes (21 bone, 3 whole brain, 2 chest), 2/3 as single fractions, finishing a median of 17 days before death. Expected survival was predictive of prescribed RT dose on univariate logistic regression, but did not retain significance on multivariate analysis. Conclusions: Despite international surveys in which prognosis has been cited as the main factor affecting treatment decisions, in this cohort, other aspects appear to have more strongly influenced palliative RT recommendations.
Incidence of radiation recall in a community cancer center.
Authors: K. Ankrom, C. L. Smith, N. Y. Gabrail
Journal: Journal of Clinical Oncology (2011)

e19640 Background: The incidence and severity of radiation complication recall is under reported, yet it is responsible for significant short and long term morbidity that can result in disabling consequences. Even prospective clinical trials often fail to address this issue since long term follow up is required to fully detect the signs and symptoms resulting from the late radiation recalls. This retrospective report details the incidence of radiation recall phenomenon in a community practice. Methods: A retrospective chart review of 334 patients using HER data relying on the diagnosis entered as radiation complications was done in one community medical oncology practice. The charts of the patients who developed significant radiation complications were reviewed for evidence of RC that was significant enough to require medical intervention. The site and number of RC events was analyzed. Results: Of the 334 charts reviewed, 139 patients were identified who developed a significant degree of radiation therapy complications. Nineteen patients (13%) developed one or more definite radiation recall. The sites of recall were as follows; 15 cases were RC complications in the chest including radiation pneumonitis, radiation esophagitis and one case of radiation carditis resulting in a picture similar to severe viral carditis causing severe congestive heart failure. Three cases had RC in the throat and one case of radiation proctitis recall. In most cases the RC was precipitated by intercurrent viral or bacterial infections. The total number of recall events was 42. Some patients developed more than one episode as follows; radiation pneumonitis 20, radiation cystitis 3, radiation proctitis 5 and radiation mastitis 7 episodes. In many patients recall affected more than one organ. Conclusions: radiation recall is a significant under reported source of morbidity in patients receiving radiation therapy for the treatment of cancer. The retrospective nature of this study probably underestimates the incidence of RC in cancer patients. Long term prospective studies are needed to fully understand the incidence and impact of this phenomenon.
Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity
Authors: Selma Boulenouar, Xavier Michelet, Danielle Duquette, David Alvarez, Andrew E. Hogan, Christina Dold, Donal O’Connor, Suzanne Stutte, Ali Tavakkoli, Desmond Winters, Mark A. Exley, Donal O’Shea, Michael B. Brenner, Ulrich von Andrian, Lydia Lynch
Journal: Immunity (2017)
Long-Term Survival and Quality of Life Assessment After Allogeneic Stem-Cell Transplantation; Comparable Results Following Myeloablative and Reduced-Intensity Conditioning,
Authors: Avichai Shimoni, Eran Tallis, Noga Shem-Tov, Yulia Volchek, Ronit Yerushalmi, Arnon Nagler
Journal: Blood (2011)
Evaluating systems of care.
Authors: Sarah Ford Duggan Goldstein, Jennifer Wisner, Carole Redding Flamm
Journal: Journal of Clinical Oncology (2012)

100 Background: Blue Cross and Blue Shield Association (BCBSA) is an association of 38 independent, locally operated Blue Cross and/or Blue Shield Plans (each, a BCBS Company). BCBSA and the 38 Blue Companies developed the Blue Distinction (BD) Program, a hospital based quality recognition program with clinical focus on six areas of specialty care, including complex and rare cancers. In 2010, BCBSA and 7 BCBS companies engaged in a pilot study with 25 systems of cancer care, to examine the feasibility of measuring key components of quality that were developed with input from a national multidisciplinary expert panel. Breast and/or colon cancer programs were examined on a range of settings, to understand similarities and differences between systems of cancer care in various regions across the country. Methods: A series of structured discussions and a three-part survey were used to gather information about systems of cancer care. The surveys explored various structures and processes of care that support multidisciplinary, coordinated, evidence-based and patient-centered care across the continuum of care. Results: A diverse group of established multidisciplinary systems of cancer care [n =17 responses (68%)] participated, representing tertiary, community, urban, and rural settings from various regions. Approximately one-third of the responding systems provided written treatment plans or written treatment summaries to patients, and less than one-half had formal processes for comprehensive survivorship care. A majority provided patient navigators, care coordination, or case management services, and a similar majority communicated with the primary care provider at identified points in course of patient’s treatment (e.g., initial assessment, change in treatment, completion of treatment). Conclusions: The pilot study identified gaps in oncology care, similar to those found by the Institute of Medicine (National Cancer Policy Board, Institute of Medicine, and National Research Council. Ensuring Quality Cancer Care. Washington, DC: The National Academies Press, 1999) and others. Opportunities exist for oncology stakeholders to promote quality improvement efforts to narrow these gaps and to improve the quality of cancer care.
Phase I trial of the investigational aurora A kinase (AAK) inhibitor MLN8237 (alisertib) in combination with docetaxel (DTX) in patients (pts) with advanced solid tumors, including castration-resistant prostate cancer (CRPC).
Authors: John Sarantopoulos, Noah M. Hahn, Celestia S. Higano, E. Jane Leonard, Bin Zhang, Xiaofei Zhou, Claudio Dansky Ullmann, Julie Nicole Graff
Journal: Journal of Clinical Oncology (2014)

217 Background: Overexpression of AAK, a key regulator of mitosis, is seen in various solid tumors, including prostate cancer. This open-label, Phase 1 trial investigated the safety/tolerability of MLN8237, an oral selective AAK inhibitor, combined with DTX in pts with advanced solid tumors, including CRPC. Methods: Previously treated pts aged ≥18 y who were candidates for DTX received 21-day cycles of MLN8237 10–50 mg BID on days 1–7, escalated in 3+3 dosing cohorts, plus DTX 60 or 75 mg/m 2 on day 1. To manage toxicity, a 5-day MLN8237 regimen was later evaluated with DTX 60 or 75 mg/m 2 + G-CSF support. Primary endpoints were safety/tolerability and recommended phase II dose/schedule (RP2D). Pharmacokinetics (PK) and antitumor activity (RECIST 1.1/PSA) were also assessed. Results: 35 pts (median age 63 y [25–87]; 71% male; 17 CRPC) recruited into 8 cohorts received a median of 3 (1–33) cycles; 15 pts (11 CRPC) had ≥6 cycles. 14 DLTs were seen in 11 pts (5 CRPC) in Cycle 1: G4 neutropenia &gt;7 days (n=3), G3/4 febrile neutropenia (FN; n=7), G3 stomatitis (n=3), and G3 urinary tract infection (n=1). The RP2D was MLN8237 20 mg BID on Days 1–7 + DTX 75 mg/m 2 in 21-day cycles without G-CSF. Common G≥3 drug-related AEs included neutropenia (86%), leukopenia (31%), FN (23%) and stomatitis (14%). 20 (57%) pts reported SAEs, most commonly FN (n=8). 2 pts withdrew due to AEs, inc. 1 death (G3 FN; G3 mucositis); 4 pts continue on study. On-study deaths (n=2; disease progression) were not considered drug-related. Steady-state MLN8237 exposure (AUC ss ) increased approximately dose-proportionally over 10–30 mg BID when combined with DTX (n=16). Analysis of the effect of MLN8237 on DTX PK at RP2D is ongoing. Among 11 evaluable CRPC pts, 6 had PR (4 had PSA50) and 6 had SD (4 with PSA50). 2 other pts (bladder cancer and angiosarcoma) also had PR. Conclusions: The RP2D was MLN8237 20 mg BID on days 1–7 + DTX 75 mg/m 2 on day 1. Despite myelosuppression, the combination of MLN8237 and DTX had a generally manageable toxicity profile in pts with advanced solid tumors. Further clinical study of this combination, particularly in CRPC pts, is warranted. Clinical trial information: NCT01094288.