tbuckley/cabot-search huggingface dataset:
Association of neutrophil-to-lymphocyte ratio with overall survival in underserved patients with pancreatic cancer.
Authors: Muhammad Umair Mushtaq, Hussein Hamad, Ankit Mangla, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2015)

e15263 Background: Inflammatory response in tumor microenvironment plays a critical role in cancer progression. The study explored predictors of poor overall survival (OS) in underserved pancreatic cancer patients, including neutrophil-to-lymphocyte ratio (NLR). Methods: A retrospective review of 168 patients diagnosed with pancreatic cancer (2005-2014) was conducted at Cook County Hospital, Chicago. Socio-demographic, clinical and pathologic factors were recorded at the time of diagnosis. Univariate and multivariate cox regression analyses were conducted to correlate factors with OS. Crude (HR) and adjusted (aHR) hazard ratios with 95% confidence intervals (CI) were obtained. Results: The study included 49% Afro-Americans, 22% Caucasians and 20% Hispanics. Median age was 58.5 years and 54% were males. Past history was significant for hypertension (48%), diabetes (37.5%), smoking (49%) and alcohol abuse (47%). Stage 4 cancer was seen in 60% patients and 63% had tumor located in the head of pancreas. Median OS was 9 months (95% CI 7.5-10.5). Median NLR was 3.1. Treatment offered were chemotherapy (55%), radiation therapy (33%), surgical resection (23%) and palliative reduction (15%) while 34% received no treatment. Stage 1-2 cancer as compared to stage 4 cancer (HR 0.31, 95% CI 0.19-0.53, P < 0.001), high lymphocyte count (HR 0.70, 95% CI 0.54-0.91, P = 0.009), chemotherapy (HR 0.41, 95% CI 0.28-0.60, P < 0.001), radiotherapy (HR 0.42, 95% CI 0.28-0.63), and surgical resection (HR 0.27, 95% CI 0.16-0.46, P < 0.001) correlated with improved OS. Location in body of pancreas as compared to head (HR 2.19, 95% CI 0.17-4.10, P = 0.014), NLR above 3.1 (HR 1.67, 95% CI 1.15-2.43, P = 0.007), and no treatment (HR 4.11, 95% CI 2.64-6.39, P < 0.001) correlated with poor OS. In multivariate model, high NLR (aHR 1.58, 95% CI 1.07-2.34, P = 0.022) predicted poor OS and surgical resection predicted improved OS (aHR 0.36, 95% CI 0.17-0.78, P = 0.009). Median OS in patients with high NLR was 7 months (95% CI 4.6-9.4) versus 10 months (95% CI 7.8-12.2) in those with low NLR (P = 0.005). Conclusions: High NLR and surgical resection of tumor were independent predictors of prognosis in underserved pancreatic cancer patients.
Biweekly gemcitabine and capecitabine in heavily pretreated patients with metastatic colorectal cancer (mCRC).
Authors: Maria Del Pilar Solis Hernandez, Paula Jiménez, Laura Faez Garcia, Carlos Alvarez Fernandez, Quionia Pérez Arnillas, David Jose Rodriguez Rubi, Ana Lucrecia Ruiz, Luisa Sánchez Lorenzo, Walter Antonio Li Torres, Esther Uriol, Maria Dolores Menendez Prieto, Jose Maria Vieitez de Prado
Journal: Journal of Clinical Oncology (2013)

e14617 Background: Some patients with mCRC are still susceptible to continue with active therapy after progression to fluoropyrimidines, oxaliplatin, and irinotecan regimens due to their good performance status. Preclinical and clinical trials suggest that gemcitabine and fluoropyrimidines are synergic antimetabolites. Their major mechanism of action is to incorporate dFdCTP into DNA and to introduce FUTP into RNA, respectively, affecting their processing and function. This study aims to describe patients profile and response to gemcitabine-capecitabine (GemCap) in heavily pretreated mCRC, and so possible predictive factors for survival. Methods: Between June 2001 and July 2011, 119 evaluable patients pretreated with oxaliplatin and irinotecan regimens were enrolled: ECOG 0-1 97%, male 68%, median age 63yo, range: 36-79, rectum 57%, 3rd line: 61%. Patients received Gem 1000 mg/m 2 d2 and Cap 1000 mg/m 2 BID x 7d q2w. Survival analysis was determined by Kaplan-Meier and log-rank test. Results: ORR and clinical benefit were: 5% and 36%. Median PFS and OS were 2.83m (0.43-35) and 6.53m (0.47m-10yrs in patient with complete response). Most frequent toxicities were anemia (22%), thrombocytopenia (10%), hand-foot syndrome (9%) and grade ≥3 were diarrhea in 5%. There were no treatment-related deaths. Predictive factors for PFS and OS are shown in Table. Statistic significance was registered in favor of clinical benefit achieved and for those who had not previously received monoclonal Abs, for SLP and OS respectively. Moreover, patients under 65yo tend to have a better survival. Conclusions: These data suggest GemCap is a tolerable regimen that achieves maintained responses for non selected heavily preated mCRC patients, especially in those reaching radiological clinical benefit, without previous use of monoclonal Abs and younger patients. [Table: see text]
Dosing patterns of octreotide LAR among elderly patients with neuroendocrine tumors: Analysis of the SEER-Medicare database.
Authors: Ying Xu, Ya-Chen T. Shih, Colleen Leary, Chan Shen, James C. Yao
Journal: Journal of Clinical Oncology (2012)

e14550 Background: Octreotide LAR is used for treatment of hormonal syndromes associated with NETs and may delay tumor progression. Although various dosages and schedules of administration have been reported, a systematic analysis has not been performed. Methods: Using the SEER-Medicare database, we identified patients diagnosed with NETs between July 1999 and December 2007. We then excluded those patients with poorly differentiated histology, under age 65 at diagnosis, enrolled in HMOs, and who did not have continuous Part A &amp; B enrollment between NET diagnosis and the end of 12 months after the initial octreotide LAR use. HCPCS codes, J2352 and J2353, were used to identify octreotide LAR from Medicare claims. For each patient, mean octreotide LAR dose per month was calculated and classified into five dosing categories, ≤ 10, 11-20, 21-30, 31-40, &gt;40 mg, for the initial 3 months and every subsequent 3 months during the first year. Results: A total of 3,543 octreotide LAR treatments were observed among 355 patients during their first year of therapy. Dose given on a single day ranged from 10 mg to 90 mg. 86 (24.2%) patients required a ≥ 30% escalation in dose during the first year of therapy. The distributions of the mean monthly doses by dosing categories for the initial 3 months and the highest use 3 months during the first year are included in the Table below. 134 (37.7%) patients required doses greater than 30 mg per month. Conclusions: Our analyses showed that patients frequently required the escalation of octreotide LAR dose during their course of illness. A substantial number of patients required doses greater than the FDA approved dose of 30 mg per month. [Table: see text]
Single-center experience in French Temporary Authorization for Use (TAU) metastatic melanoma program with ipilimumab.
Authors: Francois Chasset, Cécile Pagès, Lucie Biard, Jennifer Roux, Irina Sidina, Isabelle Madelaine, Nicole Basset-Seguin, Manuelle Viguier, Nika Madjlessi, Pierre Schneider, Martine Bagot, Matthieu Resche-Rigon, Celeste Lebbe
Journal: Journal of Clinical Oncology (2014)

e20034 Background: Ipilimumab is anti CTLA-4 antibody which is recently approved in Europe as monotherapy in the treatment of metastatic melanoma. We report a single center experience in patients treated in a Temporary Authorization for Use (TAU). Methods: This retrospective, observational study included patients between June 2010 and July 2011 with diagnosis of unresectable stage III or IV melanoma with at least one previous line of chemotherapy. Treatment consisted in four courses of ipilimumab at dose of 3mg/kg every three weeks. Aim of the study was to evaluate efficiency and tolerability in poor-prognosis population and identify which patient will benefit most. Results: 45 patients were included which 23 (51%) had brain metastasis.Best overall response rate (BORR) was 13% and median OS was of 8 months (95%CI: 7 to 12). Overall survival (OS) was not different among patients with or without brain metastases at baseline (p=0.10) or regardless BRAF V600E status ( p=0,61).Corticosteroids baseline were significantly negatively associated with OS. These result are valid for general population p<0,0001 and those with brain metastases p =0,043. OS was poorer in patients with LDH at baseline > 500 UI/ml (p=0,008). Conclusions: this is the first series finding a negatively association with OS of baseline corticotherapy. BRAF V600 E status and brain metastasis shouldn’t be barrier to the initiation of treatment contrary to high LDL rate.
Multicenter phase I/ II study evaluating maximal tolerated dosage and clinical efficacy of an association of temozolomide with Peg-Intron in patients with metastatic melanoma
Authors: O. Dereure, A. Khamari, D. Cupissol, M. Delaunay, C. Bédane, B. Dréno, B. Guillot
Journal: Journal of Clinical Oncology (2004)

7548 Background: Treatment of metastatic melanoma (MM) remains disappointing since an objective response is usually obtained in only 12 to 20% of patients. A combined approach by chemo-immunotherapy might increase the rates of response through a synergistic anti-tumoral action. Accordingly, a phase I/II clinical trial using an association of Temozolomide(TMZ) with Peg-interferon α2b (PEG) in patients with MM was designed. The first aim of this study was to determine the maximal tolerated dosage (MTD) of both drugs. A secondary objective was to evaluate the antitumoral response rate. Methods: Patients with MM in first or second line of treatment and without cerebral metastasis were enrolled in a multicenter, prospective, open-label study. Dose escalation was performed according to the MCRM scale and resulted in four different dose levels (DL) of patients. DL1 : TMZ 150mg/m2 5 d/w each 4 weeks and Peg 0.5 μg/w, DL2 : TMZ 150 mg/ m2 5d/w and Peg 1.0 μg/w, DL3 : TMZ 200 mg/ m2 5 d/w and Peg 0.5 μg/w, DL4 : TMZ 200 mg/ m2 5d/w and Peg 1.0 μg/w. Patients received a maximum of 6 cycles. Results: 31 patients were enrolled in the study. One patient was enrolled in the DL1, 1 in the DL2, 18 in the DL3 and 11 in the DL4. In the DL4 group, 4/11 patients experienced a hematologic dose-limiting toxicity(DLT) (grade IV thrombopenia) and 4 patients had non dose-limiting toxicity. These 8 patients were thereafter treated according to the DL3. An objective clinical and morphological response was observed in 4 patients (2 complete responses and 2 partial responses). Four stable diseases were observed and 8 patients were alive 9 to 19 months after enrollment (median survival: 364 days; CI 95% = 201–358). All responses were observed in the DL3–4 patients groups. Conclusion: The combination of TMZ with PEG in MM showed an hematological DLT. The maximal tolerated dose was obtained in DL3 group. The combined treatment at DL3 was effective (13% of objective response and 10% of stabilization) and deserves further investigations to define its place in the treatment of patients with MM. No significant financial relationships to disclose.
Prospective evaluation of <i>KRAS, NRAS, BRAF</i>, and <i>PI3KCA</i> mutation screening for patient enrolment in AGITG ICECREAM (Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation among Patients with G13D Mutation) trial in metastatic colorectal cancer (mCRC).
Authors: Paul Michael Waring, Jayesh Desai, Zbigniew Barney Rudzki, Kate Wilson, Val Gebski, Louise M. Nott, Christos Stelios Karapetis, Mustafa Khasraw, Craig Underhill, Nick Pavlakis, Lorraine A. Chantrill, Jeremy David Shapiro, Eva Segelov
Journal: Journal of Clinical Oncology (2014)

e14536 Background: Patients with refractory KRAS WT mCRC benefit from EGFR-inhibiting antibodies (EGFR-I). Retrospective analyses suggest tumours bearing KRAS exon 2 G13D mutations may also derive benefit. Recent data restricts the profile of responders to tumours which are WT for KRAS exons 2, 3 & 4 and NRAS. Retrospective data indicates WT PIK3CA gene may also be needed for response, whilst the predictive value of BRAFmutations is more uncertain. ICECREAM is a currently recruiting international randomised phase II trial of cetuximab +/- irinotecan in 100 patients with “quadruple WT” tumours (KRAS, NRAS, PIK3CA, BRAF) or with KRAS G13D mutation. Methods: Tumour samples were screened at any stage following mCRC diagnosis. Sanger sequencing and SNaPshot analysis (limit of sensitivity 15%, 3%) was performed for KRAS exons 2, 3 & 4, NRAS, BRAF exon 15 and PIK3CA exons 9 & 20. Results: Samples from 149 patients were screened for KRAS and 131 of those for the additional genes. Six samples failed technically. 59 of 125 (47%) were WT for all 4 genes. Mutation frequencies were: KRAS exon 2 – 45; exon 3 – 3; exon 4 - 1 (49/143 (34%)), NRAS 7/125 (6%), BRAF 13/125 (10%) and PIK3CA exon 9 – 11; exon 20 – 5; (16/125 (13%)). KRAS G13D was identified in 7 cases (5%). KRAS, NRAS & BRAF mutations were mutually exclusive whereas PIK3CA mutation frequently co-existed with KRAS mutations. Of 59 quadruple WT patients, 13 are enrolled on trial, with 27 G13D mutation patients. Sanger sequencing identified rare or unusual mutations (KRAS Q22K, KRAS V14I, KRAS T74P, BRAF D584G(2), BRAF D584N and PIK3CA M1943I) of uncertain significance in 7 cases (5%); these would be missed by allele-specific methods directed towards common hotspot mutations. Conclusions: The mutation frequencies in genes predicting sensitivity to EGFR-I in a trial- eligible community population are similar to those reported in retrospective analyses from large Phase III trials. Screening for exons rather than hotspot mutations identified rare or unusual mutations of uncertain clinical significance in 5% of patients. Clinical trial information: ACTRN12612000901808.
Primary epithelioid angiosarcoma.
Authors: Silvia Stacchiotti, Alessandro Gronchi, Massimiliano Gennaro, Elena Palassini, Chiara Colombo, Paola Collini, Roberta Sanfilippo, Rossella Bertulli, Marco Fiore, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2014)

10578 Background: Epithelioid angiosarcoma (EAS) is a rare sarcoma. Complete surgical resection, when feasible, is the mainstay of therapy. Relapse rate after complete resection of primary tumor ranges from 45 to 70%, with a median survival (OS) of about 5 years. A multidisciplinary approach combining surgery, radiotherapy (RT) and/or chemotherapy (CT) is advocated by many, but there are no definitive data on the efficacy of (neo)adjuvant CT. Methods: We retrospectively reviewed all primary, localized, completely resected EAS observed at our institution (INT) from 1/2005 to 6/2013. We considered patients (pts) in whom at least one phase of treatment (surgery and/or RT and/or CT) was performed at INT. We excluded pts not amenable to complete surgery. Diagnosis was centrally reviewed. Results: Fifty-one pts were identified (46 surgically treated at INT). M/F: 16/35. RT-related: 20. Primary tumor site: breast, 29 (skin/gland: 22/7); extremities, 10; other, 12. Single versus multifocal: 39/13. Median tumor size of monofocal lesions: 5 cm (range 1-21). 20/51 (39%) pts received RT; 31/51 (60%) pts were treated with CT, of whom 4 were unresectable at baseline and 11 multifocal. Median number of cycles: 5 (range 3-8). Regimens were: anthracycline + ifosfamide,12 pts; gemcitabine +/- taxanes, 18. Median follow-up (FU) was 34 months (range 5-96; 4 pts lost to FU). 14 pts relapsed (Local-LR/Distant-DR 4/10). All LR were observed in post-RT skin EAS. 3/10 DR occurred in <5 cm tumors. RFS and OS were 68/62% and 85/68% at 2/5 yrs. Median time to relapse was 8 months (range 2-35). Following distant relapse, OS from relapse was 22/22% at 2/5 yrs (13-month median OS). Among 31 pts treated with CT, RFS and OS were 62/62% and 88/60% at 2/5 yrs. Ten pts received GEMTAX; their RFS and OS were 75/75% and 100/100% at 2/5 yrs, as compared to the others receiving CT, whose RFS and OS were 69/50 and 83/50 at 2/5 yrs. Conclusions: In this series of 51 pts, RFS and OS were apparently better than in published studies. More than half of pts received CT. Those receiving CT had worse prognostic factors, but their outcome was similar to those who did not receive any (neo)adjuvant CT. Amongst CT regimens, GEMTAX was associated with a better outcome. In this rare sarcoma, these data suggest hypotheses to test in prospective studies.
A study of activated carbon nanoparticles guided dissection of lymph nodes in radical gastric cancer surgery.
Authors: Rajiv Prasad Keshari, Zhiwei Zhou, Gong Chen, Shuqiang Yuan
Journal: Journal of Clinical Oncology (2012)

e14674 Background: Gastric cancer is common and a leading cause of cancer deaths in the world. Lymph node(LN) status is important prognostic factor. As per AJCC, atleast 15 LNs to be dissected for accurate nodal staging and prognosis. More LNs dissections may reduce the possibility of skip metastases, thus, less recurrence and proper staging of the disease. Activated Carbon Nano-particle(AcCNP) can map a large number and even smallest lymph nodes. The objective of this study is to detect and dissect maximum number of LNs during radical gastrectomy by using AcCNP lymphatic mapping. Methods: 40 patients, Gr. A (22) experimental and B (18)control group, pathological diagnosis- Adenocarcinoma of stomach, AJCC staging I-IIIB. Time duration- 2008 to 2009, Institution- SYSUCC, Guangzhou,China, Plan- Radical Gastrectomy with extended lymphadenectomy. Neo-adjuvant given patients were excluded. A 1 ml of AcCNP was injected in the subserosa of the stomach at four different sites of the tumor border. All visible stained/nonstained LNs were dissected. The LN's size and the number were recorded. After pathological reports, descriptive analysis and t-test were performed to calculate the mean, median, ratio, range, frequency and predictive value for the accuracy and viability of the study. Results: Total LNs dissected-1254, Gr.A-772 (mean-35.41) and Gr.B- 482 (26.78). There was difference between total LNs dissected (p-value- 0.046). In Gr. A, 590 blackened and 182 non-blackened LNs resected. The ratio to the total number of LNs was ≥70%. LNs size in Gr. A was 0.03 to 0.5 cm and 0.80 to 1.5 cm in Gr. B, p-value: 0.000. No statistical differences between the two groups in age, sex, pTNM staging and histo-pathological type with p-value - 0.305, 0.369, 0.828 and 0.425 respectively, and in tumor size, Gr. A (5.59 cm) and Gr. B (3.72), p-value of 0.78. Conclusions: Lymph node detection procedure by intra-operative injection of Ac. carbon nanoparticle during radical gastrectomy is feasible in all stages of gastric cancer, with high detection rate and almost nil morbidity or mortality. It is safe, cost-effective and an effective tracer for lymphatic mapping procedure. It can be an appropriate tool for more accurate staging of gastric cancer.
Strength and endurance training in the treatment of lung cancer patients staged IIIA/IIIB/IV.
Authors: Corinna C. Henke, Jan Cabri, Lothar Fricke, Wulf Pankow, Giannis Kandilakis, Petra C. Feyer, Maike De Wit
Journal: Journal of Clinical Oncology (2012)

9033 Background: This RCT tested the effect of a specially designed strength and endurance training on the independence in activities of daily living and quality of life in lung cancer patients staged IIIA/IIIB/IV while receiving palliative chemotherapy. The aim was to break the vicious circle created through the connection of physical inactivity and the worsening of symptoms and side effects. Methods: Between August 2010 and December 2011 lung cancer patients staged IIIA/IIIB/IV with a good performance status receiving an inpatient palliative chemotherapy treatment at the Vivantes Hospital Neukölln/Berlin, were randomized into an intervention and control group. The Barthel Index and the EORTC QLQ-C30/ LC13 questionnaire were used for evaluation. The Six-Minute-Walk-Test and stair walking in combination with the Modified Borg Scale have been used to test the patient’s endurance capacity. Furthermore muscle strength was examined. Non-parametrical data were statistically analyzed with the Wilcoxon and Mann-Whitney-U test. For parametric data student t- tests were used. A significance level of p&lt; .05 was accepted. Results: Out of 46 patients, who signed the informed consent, 29 patients completed the trial (18= Intervention group, 11= Control group). Significant differences between the groups were detectable in the Barthel Index (IGmean(SD)=92.08 (15.15); CGmean=81.67 (14.98); p=.041), and in single scores of the EORTC QLQ C-30/LC-13 questionnaire (Physical Functioning p=.025; Haemoptysis p=.019, Pain in Arms or Shoulder p=.048, Peripheral Neuropathy p=.050, Cognitive functioning p=.050). Significant differences were found between the groups concerning the 6MWT, stair walking and strength capacity (IG&gt;CG). Additionally the level of dyspnoea decreased significantly in the IG while performing submaximal walking activities. Conclusions: The training program has a positive impact on the patient’s independence in carrying out activities of daily living. Although it does not have a significant impact on the patient’s quality of life, single factors can be significantly improved. Moreover it has a positive effect on the patient’s endurance and strength capacity. The dyspnoea perception is improved.
<i>BRCA1/BRCA2</i> (<i>BRCA</i>) testing in young women with breast cancer: Patterns, motivations, and implications for treatment decisions.
Authors: Shoshana M. Rosenberg, Kathryn Jean Ruddy, Rulla M. Tamimi, Shari I. Gelber, Lidia Schapira, Steven E. Come, Virginia F. Borges, Bryce G. Larsen, Judy Ellen Garber, Ann H. Partridge
Journal: Journal of Clinical Oncology (2014)

6548 Background: While BRCA testing is recommended for women diagnosed with breast cancer before age 50, little is known about decisions surrounding testing in young patients. Methods: As part of an ongoing cohort study, we surveyed 765 women diagnosed with breast cancer at age ≤ 40 about their experience with BRCA testing at approximately 1 year after diagnosis. We used Chi-square tests to evaluate differences in how genetic information was used to make treatment decisions among women who 1) tested positive 2) tested negative 3) were not tested. Among untested women, we assessed whether 1) genetic risk was discussed with a provider 2) reasons why they were not tested. Results: 655/765 (86%) of women reported undergoing BRCA testing by 1 year from diagnosis. 31% (232/746) said that knowledge/concern about genetic risk influenced treatment decisions. Among these women (Table), 87% of mutation carriers, 50% of non-carriers, and 45% of untested women chose bilateral mastectomy; fewer women reported that adjuvant treatment decisions were influenced by genetic risk concern. Among untested women, 32% (35/110) had not discussed the possibility that they might have a mutation with their doctor. The top 5 reasons cited for not testing were: patient perceived risk low (25%), doctor perceived risk low (24%), not a priority (18%), insurance/work (14%), financial (11%). 39% were thinking of testing in the future. Conclusions: >10% of women with breast cancer ≤ 40 were not tested for a BRCA mutation within a year of diagnosis. Among these women, 1/3 did not discuss genetic risk with their doctor. Given that knowledge/concern about genetic risk influences surgical decisions and can affect systemic therapy trial eligibility, all young breast cancer patients should have access to adequate genetic counseling and testing if desired. Genetic concerns influenced use/choice of treatment in the following ways. (N=232) BRCA+ N=71 N (%) BRCA- N=139 N (%) Not tested N=22 N (%) p Mastectomy instead of lumpectomy 3 (4) 14 (10) 7 (32) 0.001 Bilateral mastectomy 62 (87) 70 (50) 10 (45) <0.0001 Salpingo-Oophorectomies 37 (52) 6 (4) 2 (9) <0.0001 Endocrine therapy 12 (17) 28 (20) 4 (18) 0.78 Chemotherapy 14 (20) 17 (12) 3 (14) 0.35