tbuckley/cabot-search huggingface dataset:
Pretreatment physical activity to predict short- and long-term chemotherapy-induced peripheral neuropathy (CIPN) in a nationwide longitudinal study of paclitaxel for breast cancer.
Authors: Ian Kleckner, Eva Culakova, Jennifer S. Gewandter, Chunkit Fung, Richard Francis Dunne, Luke Joseph Peppone, Julia Ellen Inglis, Kah Poh Loh, Laura J. P. Feldman, Shaker R. Dakhil, Judith O. Hopkins, Karen Michelle Mustian, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2018)

10018 Background: CIPN is a dose-limiting toxicity with no established treatments and limited knowledge of risk factors. Exercise during chemotherapy may mitigate CIPN, but it is unknown whether pre-treatment physical activity protects against CIPN. This secondary analysis examines whether physical activity before paclitaxel predicts short- and long-term CIPN symptom severity. Methods: 200 women with non-metastatic breast cancer (52±10 years) receiving paclitaxel with curative intent rated their CIPN (0-10 severity of numbness/tingling in the past week) three times—within 1 week pre-paclitaxel, and within 1 month and 6 months post-paclitaxel. We used linear regression to test whether pre-paclitaxel patient-reported physical activity (Aerobic Center Longitudinal Study) predicted CIPN symptoms (either within 1 month or 6-months post-paclitaxel) controlling for pre-paclitaxel neuropathy, age, BMI, diabetes (yes/no), and cumulative paclitaxel dose. Results: CIPN symptom severity increased significantly from pre- to post-paclitaxel (+3.6 units; p< 0.001) and from pre- to 6-month follow-up (+2.08; p< 0.0001). This is a high level of development of CIPN considering that a 0.5-unit change is clinically significant. Each additional 15 min/day of physical activity pre-paclitaxel was associated significantly less severe CIPN symptoms at post-paclitaxel (-0.5; p= 0.0002) and 6 months follow-up (-0.25; p= 0.09). Each additional 10 years of age was associated with significantly more severe CIPN symptoms at post-paclitaxel (+0.8, p< 0.0001) and 6-month follow-up (+0.9; p< 0.0001) controlling for pre-paclitaxel neuropathy, physical activity, BMI, diabetes, and paclitaxel dose. Conclusions: Breast cancer patients who are more physically active pre-paclitaxel experience less severe CIPN immediately and 6 months post-paclitaxel. Physical activity may be especially important for older patients because CIPN severity increases with age. Clinicians prescribing paclitaxel should ask patients about pre-treatment physical activity levels because it may lead to greater treatment tolerability.
Lymph-node yield in 23,773 rectal cancer patients undergoing surgery between 2000 and 2011 and its impact on staging accuracy - Results from a nationwide observational study.
Authors: Benjamin Garlipp, Henry Ptok, Frank Benedix, Ingo Gastinger, Hans Lippert, Christiane J. Bruns
Journal: Journal of Clinical Oncology (2016)

3611 Background: Lymph node (LN) sampling in rectal cancer surgery has a prognostic impact, possibly because more pN+ cancers are correctly diagnosed if more LN are examined. However, despite increasing numbers of LN per specimen, the proportion of pN+ cases has remained largely constant in recent years. We examined the development of LN sampling in rectal cancer in Germany within a 12-year period. Methods: Data from the prospective German Quality Assurance in Rectal Cancer observational study were used. All patients undergoing radical surgery without neoadjuvant treatment from 01/01/2000 to 12/31/2011 were included. The number of LN (total and tumor-involved) per specimen, the proportions of specimens with ≥ 12 LN examined and of pN+ cases were analyzed for each year. To compensate for factors that may have impacted on LN diagnostics over the study period, results were compared between hospitals that did and did not report an increase in LN number per specimen between 2000/2001 and 2010/2011. Results: A total of 23.773 patients were analyzed. The mean number of LN per specimen increased from 16.2 to 20.8 during the study period, as did the proportion of specimens with ≥ 12 LN examined (from 73.6% to 93.2%; p < 0.001). pN+ was diagnosed in 44.1%, with non-significant variability during the study period (p = 0.130). The mean number of tumor-involved LN varied between 2.2 and 2.6 (p = 0.331). Examination of > 12 LN did not lead to a further increase in tumor-involved LN found in pT2 and pT4 specimens (p = 0.256 and p = 0.655). Only in pT3 specimens with more than 20 LN examined, a slight increase in positive LN was observed compared to specimens with only 12 examined LN. Neither in centers that did nor in those that did not report an increase in LN examined per specimen was there a significant change in pN+ cases observed during the study period. Conclusions: LN sampling became more extensive during the study period but this did not lead to significant tumor upstaging. Evaluation of > 12 LN only marginally reduces the number of missed pN+ cases. Mechanisms other than staging accuracy may be responsible for the beneficial effect of extensive LN sampling reported in studies.
Understanding patients’ and family caregivers’ preferences and attitudes towards disclosure of cancer related diagnosis and prognosis.
Authors: Arunangshu Ghoshal, Naveen Salins, Jayita Deodhar, Anuja Damani, Jayeeta Chowdhury, Arundhati Chitre, Mary Ann Muckaden, Rajendra Badwe
Journal: Journal of Clinical Oncology (2018)

e22130 Background: Understanding patients' and caregivers' preferences and attitudes about knowing the cancer diagnosis and prognosis (D&P) prevents demoralization of the patients. The Western medical practice differs from the orient, and there is little data available from India. The aim of this study was to explore preferences and attitudes of the Indian patients and family caregivers about disclosure of cancer related D&P. Methods: Cross sectional survey using a validated interviewer administered questionnaire. Newly diagnosed adult cancer patients and their family caregivers attending the oncology outpatients, having a ECOG score of 0-3 purposively recruited. Patients/family caregivers who were already counseled about the D&P or receiving active cancer treatment were excluded. The survey questionnaire had close-ended questions eliciting preferences and open-ended questions exploring attitudes. Results: 250 cancer patients and 250 family caregivers completed the survey. Patients preferred full disclosure of their D&P whereas the family caregivers preferred non-disclosure of D&P to their patients. Items related to name/ seriousness of illness (87.2% v 26.8%), treatment outcomes (90.4% v 45.6%), future course of illness (87.2% v 30.0%), future symptoms/ complications (88.8% v 36.4%) and the expected length of survival (72.8% v 8.8%) (p < .001 for all) showed significant difference. Patients felt that knowing their D&P will help them to plan for future/future treatment, be prepared, take precautions and plan for the family. Family caregivers felt that patients knowing their D&P will cause stress depression, loss of confidence and impacts future treatment. Conclusions: The study of preferences showed that patients preferred full disclosure (FD) of their D&P whereas the family caregivers preferred non-disclosure(ND) to their patients. The study of attitudes showed that patients and the family caregivers had a different outlook towards health care providers communicating D&P.
Analysis of single circulating tumor cells (CTCs) to identify resistance mutations to ALK-inhibitors in both ALK-gene and bypass oncogenic pathways.
Authors: Emma Pailler, Laura Mezquita, Vincent Faugeroux, Marianne Oulhen, Pauline Queffelec, Jordi Remon, Aurelie Honore, Mélanie Laporte, Claudio Forcato, Yann Lecluse, Ludovic Lacroix, Virginie Marty, Maud Ngocamus, Claudio Nicotra, David Planchard, Jean-Charles Soria, Nicolò Manaresi, Francoise Farace, Benjamin Besse
Journal: Journal of Clinical Oncology (2018)

12038 Background: Non-invasive methods including CTCs are crucial to develop for the implementation of precision medicine in the treatment of NSCLC. ALK-rearranged NSCLC patients develop resistance to ALK-inhibitors which manifest by genetic alterations either in the ALK-gene itself or in by-pass signaling pathways. Here, we evaluated whether resistance mutations to first-generation ALK-inhibitor crizotinib and third-generation lorlatinib could be identified using individual CTCs. Methods: The study included 17 patients at resistance to crizotinib or lorlatinib. Matched tumor-biopsies were available for 3. Two CTC isolation strategies were used. A process including Ampli1 whole-genome amplification, quality controls, multiplex PCR with two panels (Ampli1 CHPCustomBeta cancer panel and a home-made panel targeting the 13 known ALK mutations) and Ion Torrent next-generation sequencing was established. Single CTCs or pools of 2-10 CTCs and one CD45+ cell pool were analyzed for each patient. A specific bioinformatic workflow was developed to identify somatic variants including determination of positive predicted value (PPV), allele drop-out (ADO), false-positive rate (FPR). Results: PPV, ADO and FPR means were respectively > 95%, 19% and 6.10-4 in the seven first patients. A limited number of shared mutations between CTCs and matched tumor-biopsies were identified. Several CTC-private (exclusively present in CTCs and not in matched biopsies) hotspots mutations were identified including in ALK-gene such as the F1174L, F1174C or G1202R. Potential by-pass signaling pathways in other oncogenic drivers such TP53, PIK3CA and BRAF genes were also identified. A much higher degree of mutational diversity was observed in CTCs compared to tumor-biopsies. Conclusions: Using a rigorously qualified workflow, we report for the first time that resistance mutations to ALK-inhibitors can be identified in individually isolated CTCs of ALK-rearranged patients. Our data demonstrate that both "on-target" and "off-target" resistance mechanisms can be detected in individual CTCs highlighting their important mutational diversity in ALK-rearranged patients.
National trends in admissions for potentially preventable conditions among patients with metastatic solid tumors, 2004-2014.
Authors: Robert Michael Daly, Marwan S. Abougergi
Journal: Journal of Clinical Oncology (2018)

1 Background: The Centers for Medicare and Medicaid Services (CMS) has identified 10 conditions for hospitalization among patients receiving chemotherapy that are potentially preventable through appropriately managed outpatient care. CMS plans to measure hospitals’ performance based on frequency of admission for: anemia, dehydration, diarrhea, emesis, nausea, neutropenia, fever, pain, pneumonia, and sepsis. Our objective was to measure hospital utilization patterns for these conditions. Methods: Nationally representative data from the 2004 and 2014 National Inpatient Sample were analyzed. Adults with stage IV solid tumors admitted with a principal diagnosis of one of the ten conditions were identified using ICD-9 codes provided by CMS. The primary outcome was number of admissions. Secondary outcomes were total hospitalization costs, length of stay (LOS), and in-hospital mortality rate. Proportions and count data were compared using chi-square and binomial test, respectively. Results: Between 2004 and 2014, potentially preventable hospitalizations increased from 64,053 to 85,740 (p &lt; 0.01). The most frequent reason for admission was pneumonia (32%) in 2004 and sepsis (41%) in 2014. Table 1 provides the results for the year 2014 by condition. Hospitalizations for sepsis had the longest mean LOS (p &lt; 0.01), highest mean total costs (p &lt; 0.01) and most frequently resulted in death (p &lt; 0.01). Conclusions: The Department of Health and Human Services states, “Improving patients’ quality of life by keeping patients out of the hospital is a main goal of cancer care.” Despite supportive care advances, the increased frequency of hospitalization demonstrates a need for continued symptom management innovation. Infectious symptoms should be a focus of these technologies given their high prevalence, mortality and resource utilization. [Table: see text]
Autoantibody immune networks: A novel tool for the characterization of immune related events in cancer.
Authors: Hans-Dieter Zucht, Petra Ilse Budde, Solveig Konings, Lisa Steeg, Evelyn Friedrich, Claudia Gutjahr, Rosa Steil, Saurabh Bhandari, Manuel Tuschen, Peter Karl Schulz-Knappe
Journal: Journal of Clinical Oncology (2018)

e15141 Background: Immune reactions in cancer involve cellular and humoral response and defense mechanisms. For example, therapies which target CTLA-4 and PD-1/PD-L1 pathways have led to significant improvements in patient care. Cancer therapy is emerging as a personalized approach requiring dedicated biomarkers and targets in immunology. Autoantibody profiling can provide such biomarker information of the immunological potency of a patient prior and during therapy to predict or monitor immune related adverse events or treatment efficacy. We present a technology for network analysis of cancer patient autoantibody reactivity connecting autoantibody patterns with clinical and demographic data. Methods: We constructed a Cancer Immunotherapy Array to perform large-scale multiplex profiling of patient autoantibody responses using antigen-coated Luminex beads. Run in MTPs, the array permits quantification of autoantibody reactivity in serum samples against > 900 human protein antigens. Bayesian network analysis is computed to investigate pairwise relationships of autoantibodies and clinical data, which is visualized as networks. Results: > 2,500 serum samples from diverse cancers and autoimmune diseases (RA, SLE, Sjogren) and HC were screened. In cancer, formation of autoantibodies is mainly directed against hypermutated proteins, surface proteins and cytokines, with roles in cancer progression, survival, and immune related adverse events. In contrast, classical autoimmune diseases show autoantibodies directed against nuclear proteins, structural complexes, such as ribosomes and DNA binding proteins. Autoantibody markers found in cancer can have diagnostic value, especially when used as multimarker panels. More important, investigation of autoantibody markers reveal networks suggesting that autoantibodies are involved in regulation of physiological reactions during cancer progression. Conclusions: Autoantibody profiling will broaden our understanding of the mechanisms of host defense, targeted therapies and may guide the prediction of novel targets in cancer.
Management strategies for WBC growth factor use.
Authors: Michael A. Kolodziej, Erin Jacques, Leah Altieri-Alger, Karla Dalton, Julie Kendle, Elizabeth Yah, Phil Lerner, Harold Paz
Journal: Journal of Clinical Oncology (2016)

6619 Background: WBC growth factors have revolutionized the management of chemotherapy induced neutropenia and significantly reduce the risk of hospitalization for neutropenic sepsis. They have been widely adopted in routine clinical practice and represent a significant percent of the medical pharmacy spend for Aetna. Several studies and published guidelines only support their use for primary prophylaxis if the risk of neutropenic fever exceeds 17% or there are comorbidities present that increase the risk of an episode of neutropenia. Methods: In an effort to better understand the prescribing of filgastrim and peg-filgastrim, we examined claims for 2014. The agent prescribed, the associated payment allowed, the diagnoses and chemotherapy regimens associated with the use of the agent, and the comorbidity index were measured. In addition, a sensitivity analysis measuring the impact of utilization management is reported. Results: In 2014, 116,000 members received chemotherapy for cancer, included 26,000 with breast cancer/colon cancer/lung cancer (BCL). Of these, 18% of all patients and 29% of BCL patients received WBC growth factors. This resulted in $330 million paid, of which 62% of claims and 90% of dollars were spent on peg-filgastrim. WBC growth factor represented 17% of chemotherapy spend. Use of growth factor in the curative setting was defined by the presence of a surgical claim within 120 days of the use of the growth factor. By this definition, 35% of use was in the curative setting for breast cancer, 25% in colon cancer, and 14% in lung cancer. The most common chemotherapy regimens associated with growth factor use were 5FU based regimens, cyclophosphamide/doxorubicin, and carboplatin/paclitaxel. The comorbidity index for patients receiving chemotherapy with no growth factor was significantly higher than for patients receiving chemotherapy with growth factor (p = .001). As a result, introduction of a utilization management program that reduces inappropriate prescribing by 10% could generate $33 million savings. Conclusions: There is extensive WBC growth factor use outside the curative setting. Guideline concordant care yielding even modest reductions in use would result in substantial savings.
<i>BRAF</i> V600E Mutation as a Negative Prognostic Determinant in Resected Colorectal Liver Metastases—Reply
Authors: Georgios Antonios Margonis, Nikolaos Andreatos, Matthew J. Weiss
Journal: JAMA Surgery (2018)

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Patient-reported outcomes (PROs) in IMmotion151: Atezolizumab (atezo) + bevacizumab (bev) vs sunitinib (sun) in treatment (tx) naive metastatic renal cell carcinoma (mRCC).
Authors: Bernard Escudier, Robert J. Motzer, Brian I. Rini, Thomas Powles, David F. McDermott, Cristina Suarez, Sergio Bracarda, Walter Michael Stadler, Frede Donskov, Howard Gurney, Stephane Oudard, Motohide Uemura, Elaine Tat Lam, Carsten Grüllich, Beiying Ding, Tarik Khaznadar, Caroleen Quach, Elisabeth Piault, Christina Schiff, Michael B. Atkins
Journal: Journal of Clinical Oncology (2018)

4511 Background: The randomized, open-label Phase III IMmotion151 study met its coprimary endpoint in PD-L1+ patients (pts) with improvement in investigator-assessed PFS for atezo + bev vs sun (HR 0.74; median 11.2 vs 7.7 mo, P = 0.02). Encouraging efficacy was also observed in the intent-to-treat (ITT) population (HR 0.83; 11.2 vs 8.4 mo) (Motzer, ASCO-GU 2018). PROs were evaluated as secondary and exploratory endpoints to document pt perspective on overall clinical benefit for each tx. Methods: Pts received atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w (n = 454) or sun 50 mg PO QD 4 wk on/2 wk off (n = 461). Pts completed the MD Anderson Symptom Inventory (MDASI) and Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 (FKSI-19) questionnaires on days 1 and 22 of each 6 wk cycle, at end of tx, and during survival follow-up. Prespecified concepts included symptom burden (MDASI symptom severity and symptom interference with daily living) and bother from tx side effects (FKSI-19 GP5 item). Health-related quality of life (HRQoL) was also assessed (FKSI-19 total). Descriptive analyses included summary statistics for scores (effect sizes [ES] ≥ 0.3 suggest clinically meaningful differences), score changes from baseline (BL), and time to deterioration (TTD; first ≥ 2-point score increase in MDASI interference). Results: BL completion in ITT pts was > 80% and ≥ 70% until wk 57. At post-BL visits, pts receiving atezo + bev had milder and more stable symptom severity, less interference (differences in mean score ES: mean 0.3; range 0.1 - 0.5), and better HRQoL (differences in mean score ES: mean 0.4; range 0.1 - 0.6) vs pts receiving sun, who more often reported worsened interference. TTD in interference was also delayed (HR 0.56; 95% CI 0.46, 0.68): median for atezo + bev was 11.3 mo vs 4.3 mo for sun. A greater proportion of atezo + bev-treated pts reported no or little bother from tx side effects vs sun-treated pts. Conclusions: PRO data suggest atezo + bev maintained day-to-day functioning with minimal symptom interference and delayed TTD vs sun, further supporting positive benefit-risk for the combination regimen in first-line mRCC. Clinical trial information: NCT02420821.
Comparative features and overall survival in adenosquamous carcinoma, a rare tumor of the esophagus.
Authors: Michael Evans, Yuan Liu, Chuqing Chen, Theresa Wicklin Gillespie, Conor Ernst Steuer, Taofeek Kunle Owonikoko, Suresh S. Ramalingam, Jonathan Jay Beitler, Bassel F. El-Rayes, Felix Fernandez, Kristin Ann Higgins, Naresh Jegadeesh, Alyssa M. Krasinskas, Jerome Carl Landry, Dong Moon Shin, Field F. Willingham, Nabil F. Saba
Journal: Journal of Clinical Oncology (2016)

e15541 Background: Esophageal adenosquamous carcinoma (ASC) is a rare, mixed-histology tumor with aggressive clinical behavior. Having characteristics of both adenocarcinoma (AC) and squamous cell carcinoma (SCC), the two most common esophageal cancers, its behavior is poorly understood, with the current literature limited to case studies and small case series. Using the National Cancer Database (NCDB), an outcomes directory representing approximately 70% of new cancer diagnoses in the United States, we compared the largest number of known cases of esophageal ASC to AC and SCC in terms of patient demographics, clinicopathologic features, and overall survival. Methods: The NCDB was queried for patients diagnosed with esophageal ASC, AC, and SCC between 1998 and 2011. Univariate association with histologic group was analyzed using the χ2 test and ANOVA, where appropriate. Univariate association with overall survival was analyzed using Cox proportional hazard model and log-rank tests. Kaplan-Meier plots were used to compare survival by histologic group. Propensity score weighting was applied to balance demographic and socioeconomic characteristics among patients. Results: Between 1998 and 2011, 897 patients in the NCDB were identified as having esophageal ASC, 69,877 as having esophageal AC, and 34,312 as having esophageal SCC. The patients were commonly male (79.5% of ASC, 85.3% of AC, and 64.5% of SCC) and Caucasian (89.2% of ASC, 95.2% of AC, and 65.5% of SCC). The median age at diagnosis was 65 for both ASC and AC and 67 for SCC. The median size of tumor was 4.5 cm for both ASC and SCC and 4.0 cm for AC. Clinical N stage was > 1 in 58.3% of ASC, 54.6% of AC, and 53.7% of SCC. Clinical m stage was 0 in 69% of ASC, 70.9% of AC, and 75.6% of SCC. Median survival was 9.6 months in ASC, 9.7 months in SCC, and 13.5 months in AC. Two-year overall survival was 23.8% in ASC, 26.5% in SCC, and 34.6% in AC. All p < 0.001. By propensity score weighting, the overall survival hazard ratio for ASC was 1.1 when compared to SCC (95% CI = 1.18-1.01, p = 0.02), and 1.23 when compared to AC (95% CI = 1.33-1.15, p < 0.001). Conclusions: ASC is a rare tumor subtype among esophageal carcinomas with aggressive clinical behavior and a prognosis worse than either AC or SCC.