tbuckley/cabot-search huggingface dataset:
Reactive oxygen species in patients with ovarian adenocarcinoma treated with platinum based chemotherapy.
Authors: Anghel Rodica Maricela, Laurentia Gales, Maria Iuliana Gruia, Raluca Alexandra Trifanescu, Fabiana Curea, Inga Botnariuc, Oana Trifanescu
Journal: Journal of Clinical Oncology (2017)

e17047 Background: Ovarian adenocarcinoma (OA) is the most lethal of gynecologic tumors because women generally present with advanced stage disease. Platinum-based chemotherapy plays a pivotal role in OA treatment. The aim of the study was to assess the role of oxygen species in patients with OA and the effects of platinum based chemotherapy on blood redox status. Methods: Twenty three patients with advanced stage IIIC or IV OA who underwent platinum salts chemotherapy were included. Blood sample were collected before treatment, at 21 days (second cycle of chemotherapy) and at 42 days (3 rd cycle) and at 63 day (4 th cycle) with a platinum salt (cisplatin or carboplatin). Biochemical determination of oxidative stress was made by mesuring lipid peroxidation index (LPI), the enzymatic activity of ceruloplasmin and the thiol albumin groups. Results: Median age at diagnosis was 52 years, and 47.8% of patients presented with stage IIIC and 52.2% with stage IV. Nine patients received for the first time platinum based chemotherapy and 14 received multiple lines of chemotherapy. Response rate after 4 cycles were partial in 30%, stable disease in 57%, and progression disease in 13%. Mean value (± SD) of lipid peroxides was 6.81±1.μmol/100 ml (normal value 0-4), and of ceruloplasmin 156 ± 66 UI (normal value 80-120) which showed an increase of the final products of lipid peroxidation. Thiol mean value was 296±124 μmol/l (normal value 370- 450). The evolution of these reactive oxygen species were monitored during chemotherapy cycles. Decrease of the lipid peroxidation after 1st cycle was noticed, (7, 6.89, 5.87, 6.61), because platinum salt can bind peroxyde and this can be considered a marker of effectiveness of treatment.The thiol levels increased from one cycle to other (233, 311, 384, 393) showing that the cell is trying to contracarete the oxidative stress. Conclusions: Tumors produces reactive oxygen species in excess in patients with advanced OA. Platinum based chemotherapy in patients with OA induces radical formation and the dynamic of these markers may be used to monitor response to treatment.
Survival profile in breast cancer molecular subtypes without systemic and locoregional treatment.
Authors: Sherry X. Yang, Eric Polley
Journal: Journal of Clinical Oncology (2017)

11599 Background: It is unclear whether survival varies among breast cancer molecular subtypes without systemic and locoregional therapy. This study aims to evaluate the survival profile by molecular subtypes after surgery. Methods: In total, we evaluated 301 women with invasive breast cancer with stage I, II or III disease. Patients were classified into four major breast cancer subtypes by immunohistochemistry/FISH classifiers: luminal-A (ER+ and/or PR+/HER2-), luminal-B (ER+ and/or PR+/HER2+), HER2-enriched (HER2+/ER-/PR-) or basal-like (ER-/PR-/HER2-; triple-negative). Overall survival (OS) was analyzed by Kaplan-Meier analysis, and log-rank test for differences. Association between clinical outcome and subtype adjusting for breast cancer prognostic factors was assessed by multivariable Cox proportional hazards model. Results: All patients did not receive systemic chemotherapy and hormone therapy as well as radiation therapy. Luminal A was the most common subtype (N = 224), followed by basal-like (N = 43), luminal B (N = 21) and HER2-enriched (N = 13). Median follow-up for OS was 197 months (range: 1 – 273 months). Age at diagnosis was statistically different among the subtypes, with basal-like and luminal B having high proportions less than 50 years (P = 0.047). Patients with basal-like and HER2-enriched had more high grade tumors (P &lt; 0.001). Notably, there was no difference in OS among the four subtypes (log-rank P = 0.983). In multivariable analysis, the adjusted hazard ratio (HR) was 1.1 for luminal A vs. luminal B (P = 0.781), 0.62 in luminal A vs. HER2-enriched (P = 0.273), or 0.67 in luminal A vs. basal-like (P = 0.158). In contrast, the adjusted HR were 2.2 in age less than 50 years (P = 0.0017), and 1.1 for number of positive nodes (P = 0.00074). Conclusions: OS, through long-term clinical follow-up, is not significantly different among molecular subtypes if not controlling for other prognostic factors in patients who only received surgery. Age and number of positive nodes are independent prognostic factors in patients with no systemic and locoregional treatments.
A new prognostic model of survival in second-line targeted therapy (TT) for metastatic renal cell carcinoma (mRCC).
Authors: Lisa Derosa, Mohamed Amine Bayar, Laurence Albiges, Christophe Massard, Yohann Loriot, Karim Fizazi, Gwenael Le Teuff, Bernard J. Escudier
Journal: Journal of Clinical Oncology (2016)

e16113 Background: Current prognostic models for second-line TT in mRCC, from Memorial Sloan-Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) do not take into account tumor burden (TB) and response to first line. We aimed to develop a new model including these parameters. Methods: Data from patients treated with TT in prospective clinical trials between 2005 and 2013 at Gustave Roussy were collected. The endpoint was overall survival (OS) from second-line TT. Tumour shrinkage during first-line TT, time from first to second-line TT, TB at time of second-line TT, number and new metastatic sites prior to second-line TT were investigated in addition to IMDC factors (time from diagnosis to treatment (DTT), Karnofsky performance status (KPS), serum corrected calcium (Ca) and hemoglobin concentration (Hgb), neutrophil (Neu) and platelet count (Plt)). Potential covariates were selected using a backward Cox regression model. The added value (likelihood-ratio, LR) and the discriminant ability (C-index) of the developed model were estimated. A prognostic score was built. Results: 222 patients were included. The median follow-up was 49.4 months (mos). Prognostic factors for OS were DTT ( ≥ vs < 12 mos), KPS ( ≥ vs < 80), Hgb ( ≥ vs < limit of normal (LN)), Neu ( ≥ vs < LN), Plt ( ≥ vs < LN), TB ( ≥ 10 vs < 10 cm; HR(95%CI) = 1.43(1.03;1.99), p = 0.033), time from first to second-line ( ≥ vs < 12 mos; HR(95%CI) = 0.59(0.43; 0.81), p = 0.0012). The likelihood-ratio test comparing the new model to IMDC was significant (p = 0.003) (Table 1). The prognostic score defined 3 risk groups (good, intermediate and poor) with HR intermediate vs good = 2.353; 95%CI = (1.560; 3.547) and HR poor vs good = 5.927; 95%CI = (3.742; 9.388) with median OS (95%CI) of 42.2 mos (25.5; NR), 17.3 mos (12.9; 23.2), and 6.9 mos (5.2; 10.2) in the favorable, intermediate and poor risk group, respectively. Conclusions: We showed the added prognostic values of TB and the time from first to second line TT. This could improve the outcome prediction for second-line TT in mRCC. External validation is ongoing. MSKCC IMDC New model c-index 0.633 0.685 0.704 Likelihood-ratio difference (95%CI) * 11.4 (3.15; 23.21) p = 0.003
Understanding patient and physician perceptions of cell and gene therapy in oncology: A pilot study using qualitative interviews and social media data.
Authors: Ramesh Arjunji, Evie Merinopoulou, Zaneta Balantac, Eric Faulkner, Carla Dias-Barbosa, Daryl S. Spinner, Owen Cooper, Peter Chongpinitchai, Ashley Duenas, Amanda Bruno, Asha Hareendran
Journal: Journal of Clinical Oncology (2018)

e21194 Background: Cell and gene therapies (CGTs) offer the potential to transform oncology treatment in terms of efficacy/ effectiveness and durability of response. Given their novelty in oncology and limited patient and clinician experience with these therapies, little is known on how CGTs are perceived and how decisions are made about their use. This pilot study aimed to explore current perceptions of CGT in oncology through qualitative interviews and social media data mining. Methods: The study included 20 cancer patients and 20 oncologist interviews in the US (25% CGT-experienced) using semi-structured guides. Social media data was manually extracted from websites including posts from oncology forums and online transcripts from clinician discussions. Several key themes related to user perceptions and experiences of CGT emerged from analysis, including information on treatment expectations, perceptions of treatment risks and benefits, CGT decision drivers and administrative considerations for successful implementation. Results: In interviews, a variety of considerations relating to decision making criteria for CGT were shared, highlighting concerns and expectations about CGT; these criteria elucidated valuable insights on opportunities for stakeholder education and enhancing value and access of oncology CGT. In social media search, 302 patient posts and 36 clinician transcripts were analyzed from extracted social media data. Patients frequently discussed published CGT materials focused on efficacy and long-term survival; little discussion focused on trial experience and side effects. Clinician online discussion topics focused on CGT administration, patient eligibility, access and cost, efficacy and safety. Conclusions: The results of this pilot study may inform future research to explore emerging trends as well as inform patient and clinician education, development of clinical practice tools and potentially trial methods. These results provide valuable insights on patient and clinician perceptions of CGT that may help address key challenges of CGT such as affordability, accessibility and implementation into clinical practice.
Potentially avoidable hospitalizations in patients with advanced cancer.
Authors: Connor Johnson, Yian Xiao, Areej El-Jawahri, Risa Wong, Sara D'Arpino, Samantha M.C. Moran, Daniel E Lage, Brandon Temel, Margaret Ruddy, William F. Pirl, Lara Traeger, Inga Tolin Lennes, Barbara J. Cashavelly, Holly S Martinson, Vicki Jackson, Joseph A. Greer, David P. Ryan, Ephraim P. Hochberg, Jennifer S. Temel, Ryan David Nipp
Journal: Journal of Clinical Oncology (2017)

e18275 Background: Cancer patients and their clinicians often wish to avoid preventable hospital admissions, but efforts to understand the predictors of avoidable hospitalizations are lacking. We sought to examine reasons for hospital admissions in patients with advanced cancer, identify potentially avoidable hospitalizations (PAH), and explore predictors of PAH. Methods: We prospectively enrolled hospitalized patients with advanced cancer from 9/2014 - 11/2014 as part of a longitudinal data repository to define symptom burden in this population. Upon admission, we assessed patients’ symptom burden (Edmonton Symptom Assessment System [ESAS]; scored 0-10). We created a summated ESAS physical symptom variable. We used consensus-driven medical record review to identify the primary reason for each hospital admission and categorize it as PAH or not based on of an adaptation of Graham’s criteria for PAH. We used mixed multivariable logistic regression analyses to identify predictors of PAH. Results: We assessed 477 hospital admissions in 200 consecutively admitted patients (mean age = 64.6; 47% female; 67% married). Over half of admissions came through the emergency department (56%). The most common reasons for admissions were fever/infection (30%), symptoms (26%), and planned admission for chemotherapy or procedure (10%). We identified 149 (31%) as PAH. Among these PAH, 45 (30%) were readmissions due to failure of timely outpatient follow-up (within 7 days of discharge) and 44 (30%) were due to premature discharge from prior hospitalization. In a mixed logistic regression model, being married (odds ratio [OR] 0.48 [0.28-0.81]; p &lt; 0.01) was associated with lower likelihood of PAH, while higher physical symptom burden (OR 1.02 [1.00-1.04]; p = 0.04) was associated with greater likelihood of PAH. Conclusions: We identified that a substantial proportion of hospitalizations in patients with advanced cancer are potentially avoidable, often related to failure of timely outpatient follow-up and premature hospital discharge. Our results demonstrate that patients’ symptom burden predicts PAH, thus underscoring the need to address patients’ symptoms in order to reduce preventable hospital admissions.
Lanreotide depot (LAN) for symptomatic control of carcinoid syndrome (CS) in neuroendocrine tumor (NET) patients previously responsive to octreotide (OCT): Subanalysis of patient-reported symptoms from the phase III elect study.
Authors: George A. Fisher, Rodney F. Pommier, Edward M. Wolin, Pamela L. Kunz, Nilani Liyanage, Susan W. Pitman Lowenthal, Beloo Mirakhur, Montaser F. Shaheen, Aaron Vinik
Journal: Journal of Clinical Oncology (2017)

4088 Background: In ELECT, LAN significantly reduced the need for short-acting OCT rescue therapy for symptomatic control of CS in NET patients (pts) vs placebo (PBO) (primary result). Here we present flushing and diarrhea symptom data and biochemical response for pts with or without prior OCT use from ELECT. Methods: Adults with histopathologically-confirmed NET and history of stable CS (diarrhea and/or flushing) who were OCT-naive or responsive to OCT long-acting release (LAR) (≤30 mg q4W) or short-acting OCT (≤600 μg daily) were randomized to LAN 120 mg (SC q4W) or PBO for 16 wks. Pts administered SC OCT if needed and recorded daily frequency and severity of symptoms using Interactive Voice/Web Response System for 1 month pre-randomization and throughout the study. 24-hr urinary 5-hydroxindoleacetic acid (5HIAA) and plasma chromogranin A (CgA) were assessed at baseline and wk 12. Results: Of 115 pts randomized, 51 were OCT-naive and 64 received prior OCT. The least squares (LS) mean percentages of days with moderate/severe diarrhea and/or flushing were lower in both naive and prior OCT LAN pts vs naive and prior OCT PBO pts; LS mean difference (LAN-PBO) was significant in the naive group (Table). By week 12, 5HIAA and CgA levels dropped by ≥30% to normal in 35.3% and 15.8% of naive LAN pts and 28.6% and 4.5% of prior OCT LAN pts; 5HIAA and CgA reductions were seen in 15.4% and 21.4% of naive PBO pts and 5HIAA in 7.1% of prior OCT PBO pts. Conclusions: Pts showed improvement in CS symptoms of flushing and diarrhea and reduction in 5HIAA levels with LAN treatment, indicating efficacy of LAN regardless of prior OCT use. Transition from OCT to LAN was well tolerated among prior OCT pts in ELECT. Clinical trial information: NCT00774930. [Table: see text]
Preemptive versus reactive management of EGFR rash among mCRC patients treated with panitumumab: Results of a national survey of treating oncologists in the United States.
Authors: Kimberly Lowe, Kristina Hool, Tamer Garawin, Rachel Bergstresser, George Kafatos, Michelle McNamara, Seth Collins, Bruce A. Bach
Journal: Journal of Clinical Oncology (2017)

e15169 Background: The Skin Toxicity Evaluation Protocol with Panitumumab (STEPP) and the Japan Skin Toxicity Evaluation Protocol with Panitumumab (J-STEPP) were open-label, randomized trials that were designed to evaluate differences in preemptive versus reactive management of dermatologic toxicities associated with panitumumab among patients with mCRC. The objective of this study was to evaluate if there were differences in the knowledge and application of STEPP and J-STEPP among oncologists who self-identified as primarily managing EGFR rash preemptively or reactively. Methods: A total of 250 practicing oncologists who had treated at least three new or continuing mCRC patients with panitumumab in the last year completed an online survey to report their opinions and perceptions regarding the management strategies for mCRC patients who are treated with panitumumab. Preemptive treatment was described in the survey as beginning treatment “prior to the appearance of rash” and reactive treatment was defined as beginning treatment “after signs of rash.” Results: Of the 250 oncologists who participated in this study, n = 58 (23%) reported treating 100% of their patients preemptively and n = 38 (15%) reported treating 100% of their patients reactively. A significantly higher proportion of preemptive treaters than reactive treaters reported following the skin management strategies from STEPP or J-STEPP when managing panitumumab-related skin toxicity (31% vs 13%, p = 0.02). When asked if skin moisturizer, sunscreen, over-the-counter topical steroids, prescription topical steroids, oral antibiotics, topical antibiotics, or UV protective garments were most critical in the preemptive management of panitumumab-related skin toxicity, preemptive treaters more likely to report using oral antibiotics and reactive treaters more like to report using sunscreen (p = 0.05). Conclusions: The results of this survey highlight the wide variability in the management of EGFR-related rash among mCRC patients who are treated with panitumumab and they highlight the need for heighted education among oncologists who treat mCRC patients with panitumumab.
Updated results of a phase II study of gemcitabine, erlotinib, and S-1 in patients with advanced pancreatic cancer.
Authors: Boram Han, Hyeong Su Kim, Dae Ro Choi, Byoung Yong Shim, Kyung Hee Lee, Jin Won Kim, Jung Han Kim, Jung Hoon Kim, Ho Young Kim, Hunho Song, Choong Kee Park, Sung Hoon Moon, Jong Hyeok Kim, Jang Yong Jeon, Jung Woo Lee, Dae Young Zang
Journal: Journal of Clinical Oncology (2017)

e15778 Background: Gemcitabine-based chemotherapy is considered as a standard front-line treatment for patients with advanced pancreatic cancer. Although addition of erlotinib or S-1 to gemcitabine has yielded better outcomes, it has showed just modest improvement in survival. To overcome this limitation, we evaluated the efficacy and safety of the combination of gemcitabine, erlotinib, and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically proven locally advanced, recurrent or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine at 1,000 mg/m 2 was administered intravenously on day 1, and 8, erlotinib at 100 mg/day was administered on days 1-21, and S-1 at 60 mg/m 2 was administered on days 1-14 every 21 days and continued to maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m 2 was permitted from second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1–8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 32 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and disease control rate was 71.9% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.8-4.6 months) and 6.7 months (95% CI, 3.4-9.9 months), respectively. Conclusions: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer. Clinical trial information: NCT01693419.
The Breast Cancer Weight Loss (BWEL) trial: Randomized phase III trial evaluating the role of weight loss in adjuvant treatment of overweight and obese women with early-stage breast cancer (Alliance A011401).
Authors: Jennifer A. Ligibel, William Thomas Barry, Catherine M. Alfano, Dawn L. Hershman, Melinda L Irwin, Marian Neuhouser, Cynthia A. Thomson, Linda Delahanty, Elizabeth Frank, Patricia Spears, Electra D. Paskett, Judith O. Hopkins, Vanessa Bernstein, Vered Stearns, Julia R. White, Thomas Wadden, Pamela Jean Goodwin, Lisa A. Carey, Ann Partridge, Eric P. Winer
Journal: Journal of Clinical Oncology (2018)

TPS598 Background: Obesity is a growing health problem in the Unites States and around the world. Excess body weight has been linked to both an increased risk of developing breast cancer and poor prognosis in women diagnosed with early stage disease. A recent meta-analysis of 82 studies demonstrated that risk of breast cancer mortality was increased by 35% in women who were obese at the time of breast cancer diagnosis compared to women who were of normal weight. The Breast cancer Weight Loss (BWEL) study will evaluate the effect of weight loss after breast cancer diagnosis on risk of cancer recurrence. Methods: BWEL is a Phase III randomized trial evaluating the impact of a telephone-based weight loss intervention vs control on invasive disease-free survival (iDFS) in 3136 overweight and obese women with Stage II-III breast cancer. Eligibility criteria include diagnosis of hormone receptor positive or triple negative breast cancer within the preceding 12 months, body mass index of ≥27kg/m2, and completion of surgery, chemotherapy, and radiation (if administered). Participants are randomized to a 2-year telephone- and mail-based weight loss intervention, adapted from the Diabetes Prevention Program, plus a health education program or to a health education alone control group. The study has 85% power, using a one-sided Type I error rate of 0.025, to detect a hazard ratio of 0.80 between groups. This equates to a 4.1% absolute reduction in iDFS events in the intervention group vs. controls. Secondary aims will evaluate the impact of the weight loss intervention upon overall survival, weight and body composition, and patient-reported outcomes. Fasting blood is collected serially over time, and tissue samples of malignant and benign breast tissue are collected at baseline to provide insight into the biologic mechanisms linking obesity and breast cancer. BWEL opened in September 2016. To date, 1015 patients have been randomized and more than 1100 sites in the US and Canada have activated the trial. Support: U10CA180821, U10CA180882, U10CA180820, U10CA180868, U10CA077202. Clinical trial information: NCT02750826.