tbuckley/cabot-search huggingface dataset:
Polypectomy or surgery for malignant colonic polyps: Do we need to change the NCCN guidelines?
Authors: N. Wasif, J. S. Tomlinson, M. A. Maggard, A. E. Giuliano, C. Y. Ko
Journal: Journal of Clinical Oncology (2009)

4031 Background: Colonoscopic screening and appreciation of the adenoma-carcinoma sequence have led to increased detection and removal of colonic polyps. The National Comprehensive Cancer Network (NCCN) considers polypectomy alone to be adequate therapy for low-grade invasive T1 polyps that are limited to the head/stalk region and can be excised with negative margins. We examined the implications of this guideline for the general population. Methods: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database (1988–2003) was queried to identify patients with invasive T1 colonic polyps. Patients treated with a polypectomy (PP) were compared with those who received a surgical resection (SR). Results: Of 9,162 patients with invasive T1 colonic polyps, 61.6% (11,812) underwent SR and 38.4% (7,350) underwent PP. The percentage of polyps removed increased from 4.2% (812) in 1988 to 9% (1739) in 2003. Patients undergoing SR vs. PP had larger polyps (median size 1.3 vs. 1.0 cm, p &lt;0.001) and higher grade tumors (8.6% vs. 4.7%, p &lt;0.001). The percentage of node positivity was 7% after SR, or 8.9% if at least 12 nodes were resected. The percentage of node positivity reached a surprising 6% in 1,478 patients who underwent SR for low-grade polyps limited to the head/stalk, and nodal status significantly affected the 3-year disease-specific survival of this subgroup: 83% with nodal metastases vs. 96% without nodal metastases (p &lt; 0.003). Conclusions: Malignant colonic polyps with favorable histological features have a 6% risk of lymph node metastases even when removed with negative margins, bringing into question the NCCN recommendation that PP alone is adequate therapy. No significant financial relationships to disclose.
Role of concurrent chemoradiotherapy in organ preservation for locally advanced head and neck cancer
Authors: N. Savaraj, V. Dinh, L. Chua, P. Bustillo, K. Nissim
Journal: Journal of Clinical Oncology (2009)

e17044 Background: Optimal management for head and neck cancer is controversial. Standard of care has been surgery followed by radiotherapy, but is done with the risk of organ resection. The VA larynx study, EORTC 24891, and 91–11 US Intergroup trial have shown that chemoradiotherapy is comparable to surgery with radiotherapy in laryngeal cancers while preserving organ function. It is unclear, though, whether this could be accomplished in other tumor sites without sacrificing locoregional control and/or survival. Methods: We performed a retrospective chart review of patients who were treated at the Miami VA Medical Center with chemoradiotherapy for advanced staged head and neck cancers from 1996 to 2008. The majority of patients (84%) received 5FU and cisplatin. The choice of chemoradiotherapy was either determined by patients’ choice or their comorbidities, such as pulmonary disease and cardiac disease, precluded them from undergoing major surgery. Primary endpoints included death, relapse rates, and disease-free survival; secondary endpoints were toxicities associated with treatment and diminished organ function. Results: A total of 62 patients were included. Out of these patients, 52% had stage III disease and 50% had primary sites in the oropharynx; the remaining included larynx and hypopharynx. 20% of patients required salvage neck dissection. Complications included severe mucositis (69%), dysphagia (19% short term, 34% long term), hoarseness (13%), and dry mouth (24%). 27% had relapse of disease and median time for disease-free survival was 26 months. A total of 35 patients had died with a 2-year survival rate of 59.6%. Overall survival was best for laryngeal and oropharyngeal cancer (63 and 46 months, respectively) compared to hypopharyngeal cancer (22 months). Conclusions: Concurrent chemoradiotherapy is a valid option for treatment of locally advanced head and neck cancers especially for laryngeal and possibly oropharyngeal primaries with significant but tolerable toxicities. Although organ preservation is possible for the majority of patients with locally advanced head and neck cancer, however, the poor survival seen in hypopharyngeal cancer needs further investigation. No significant financial relationships to disclose.
Risk factors for suicidal behavior in borderline personality disorder
Authors: P H Soloff, J A Lis, T Kelly, J Cornelius, R Ulrich
Journal: American Journal of Psychiatry (1994)

This study identified potential risk factors for suicidal behavior in patients with borderline personality disorder defined by the Diagnostic Interview for Borderline Patients and by DSM-III-R criteria for patients who did and did not attempt suicide.Histories of suicide attempts and attempt characteristics were obtained by Schedule for Affective Disorders and Schizophrenia interviews from 84 patients with borderline personality disorder and were related to severity of borderline pathology, diagnostic comorbidity, and state and trait symptoms.There were 61 patients with a lifetime history of suicide attempts (72.6%), with an average of 3.39 (SD = 2.87) attempts per patient. Attempters were significantly older than nonattempters, with more impulse actions, antisocial personality disorder comorbidity, and state depression. State depression was significantly less severe in patients who had attempted suicide in the present episode (or past year) than in patients who had attempted suicide only in the past. A comorbid diagnosis of major depression, alcoholism, or drug use disorder did not distinguish attempters from nonattempters. Suicide attempt in the present episode was best predicted by the number of prior lifetime attempts. A highly serious intent to commit suicide was predicted by the number of lifetime attempts and subjective depression, while a low intent was predicted by a mixed subtype of borderline personality disorder plus schizotypal personality disorder and paranoid ideation. A high degree of medical lethality was predicted by number of lifetime attempts, older age, and hysteroid dysphoria, while low lethality attempts were associated with high degrees of anger.Risk factors for suicidal behavior in patients with borderline personality disorder include older age, prior suicide attempts, antisocial personality, impulsive actions, and depressive moods but not comorbid affective disorder, alcoholism, or drug use disorders.
Correlation of efficacy between EGFR gene copy number and lapatinib/capecitabine therapy in HER2-positive metastatic breast cancer.
Authors: A. Fabi, A. Di Benedetto, R. Merola, G. Metro, M. Mottolese, P. Papaldo, G. Ferretti, P. Vici, I. Sperduti, F. Cognetti
Journal: Journal of Clinical Oncology (2010)

1059 Background: Lapatinib (L) is a selective dual EGFR and HER2 inhibitor. In HER2-positive metastatic breast cancer pretreated with trastuzumab-based therapies, the association of L + capecitabine (C) showed superior response rate (Rr) and progression-free survival (PFS) over C alone. We analyzed the correlation between EGFR gene copy number (GCn) and clinical outcome in a population treated with L 1,250 mg p.o. daily plus C 2,000 mg/m2 p.o. days 1-14 q 21. HER3 status by immunohistochemistry was also evaluated. Methods: EGFR GCn was assessed by FISH analysis in paraffin-embedded tissue blocks from HER2-positive patients who had failed at least one trastuzumab-based therapy in the metastatic setting. EGFR gene status was scored as: the mean value of EGFR GCn per nucleus, the mean ratio between EGFR and chromosome 7, and the percentage of cells displaying > 5 EGFR GCN. A receiver operating characteristic (ROC) analysis was set up to define the cut-off of mean EGFR GCn. A value > 3.36 was able to discriminate responders versus nonresponders. Primary end point of the study was identification of the EGFR FISH score that could best predict Rr. Results: Among 44 patients treated with L+C, 37 were evaluable for EGFR FISH analysis. No sample displayed a homogeneous amplification of the EGFR gene by ratio (EGFR gene/CEP 7 ≥2). Patients characteristics were: median age 53 (range 28-75), visceral disease in 34 patients (85%), median number of previous trastuzumab-based therapies was 2 (1-5). Mean EGFR GCn was > 3.36 in 13/37 patients. These patients showed a significantly higher Rr (n=9/13; 69%) compared to those with mean EGFR GCn ≤ 3.36 (n= 4/13; 30%), (p=0.009). The status of HER3 was not associated with response. No significant differences in terms of both PFS and overall survival according to EGFR GCn were seen (p=0.90 and p=0.52, respectively). Conclusions: High EGFR GCn may predict for increased sensitivity to L + C. HER3 protein overexpression does not seem to correlate with response to L + C. This is the first report associating increased EGFR GCn with response to L. These results warrant further investigation. No significant financial relationships to disclose.
A phase I clinical trial with weekly irinotecan (IRI) and capecitabine (CAP) in patients with advanced gastrointestinal and other solid malignancies
Authors: D. T. Friedman, S. Goel, K. Desai, D. Verdier-Pinard, A. Kaubisch, A. Bulgaru, F. Camacho, G. Goldberg, S. Mani
Journal: Journal of Clinical Oncology (2004)

2113 Background: In vitro studies demonstrate synergy between fluoropyrimidines and IRI. We conducted a phase I study to evaluate the safety and tolerability of a convenient dosing schedule for the combination of IRI with an oral fluoropyrimidine, CAP. Methods: Thirty-one patients (pt), median age 60 years, performance status 0–1 (97%), prior chemotherapy 30 pt (97%), primary cancer: ovarian (7), breast (5), colorectal (4), others (15) have received 111 cycles (range 1–11) in 6 dose cohorts. IRI 75–115 mg/m2 was administered on days 1 and 8, as a 30-minute intravenous infusion, without prophylactic atropine, every 21 days (1 cycle). CAP 1500–2000 mg/m2/day was administered in 2 divided doses on days 1–14. Results: There was no cycle-1 dose limiting toxicity (DLT) observed at the first 4 dose cohorts. At dose level 5 (IRI 100 mg/m2 / CAP 2000 mg/m2), among the 12 pts entered, one pt developed cycle-1 DLT - grade 3 diarrhea and vomiting. At the next higher dose level (IRI 115 mg/m2 / CAP 2000 mg/m2) 1 of 3 pts developed grade 4 neutropenia associated with fatal gram-negative sepsis in cycle-1. Overall, across all cycles and all dose levels, grade 3 toxicities observed were diarrhea (5 pt), vomiting (2 pt), fatigue (1 pt), neutropenia (3 pt), anemia (3 pt), and hand-foot syndrome (1 pt). Acute toxicities observed within hours of IRI infusion included abdominal cramping (2 pt), diarrhea (1 pt), and salivation (1 pt), that resolved with, and did not recur in subsequent infusions with prophylactic atropine. Anti-tumor responses included partial response in 6 of 22 evaluable (27%) patients (2 breast, 3 ovarian, 1 cervical), a minimal response (1 pt), and a decrease in CA-125 (1 pt). Conclusions: The combination of IRI and CAP is safe, convenient, and well tolerated. This study is ongoing, and expansion at dose level 6 will continue. There is anti-tumor activity in otherwise chemotherapy-refractory patients, and this combination warrants further evaluation in breast and ovarian cancer, among other malignancies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer; Roche
Phase I trial of temsirolimus (TEM) plus sorafenib (SOR) in advanced hepatocellular carcinoma (HCC).
Authors: R. K. Kelley, H. S. Nimeiri, M. T. Vergo, K. Chia, M. F. Mulcahy, E. K. Bergsland, A. H. Ko, P. N. Munster, A. B. Benson, A. P. Venook
Journal: Journal of Clinical Oncology (2011)

296 Background: SOR prolongs survival in patients (pts) with HCC. In preclinical studies, mammalian target of rapamycin (mTOR) inhibitors (I) impair HCC growth and angiogenesis. Adding mTOR-I to SOR augments antitumor effect. Phase I studies of mTOR-I plus SOR have shown tolerability but did not include cirrhotic pts. We developed a phase I trial of mTOR-I TEM plus SOR to determine safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) in pts with HCC. The study was approved and funded by the National Comprehensive Cancer Network (NCCN). Methods: Eligibility: Advanced HCC diagnosed histologically or clinically. No prior systemic therapy (Tx). Prior resection/local Tx permitted if ≥1 measurable site. ECOG score ≤2, Child-Pugh ≤7, bilirubin ≤2 mg/dL, platelets ≥75,000/mcL. Design: 3+3 escalation to MTD with dose-limiting toxicity (DLT) window 28 days; 6 pts at MTD for pharmacokinetics (PK). Endpoints: 1°: MTD, RP2D. 2°: Safety, toxicity, PK. Results: 9 pts enrolled to date: 7 at DL1, 2 at DL-1. Toxicity: DL1: 1 DLT of Gr3 thrombocytopenia. 1 pt removed for hypertensive urgency, adjudicated not Tx-related. 1 pt not evaluable due to abscess. 1 pt removed for Gr3 hypersensitivity to TEM in cycle 2. All remaining pts required reduction and/or delay for adverse events (AE). Tx-related AE at DL1 include: fatigue 57%, Gr3 11%; weight loss 22%, all Gr1; anorexia 57%, all Gr1/2; diarrhea 71%, all Gr1/2; rash/hand-foot syndrome 71%, Gr3 11%; thrombocytopenia 57%, Gr3 11%; hypophosphatemia 77%, Gr3 57%, refractory 11%. Study de-escalated to DL-1 due to non-DLT cumulative AE. DL-1: 2 pts enrolled have not had DLT nor dose reduction to date. Response: 4 of 7 pts in DL1 were evaluable. 3 of 4 had stable disease as best response. Conclusions: Tx-limiting, class-related AE occurred at DL1 of this double-biologic regimen. MTD in pts with Child-Pugh Class A cirrhosis appears lower than in pts without liver disease. Tolerability and dose delivery must be achieved to determine efficacy. A phase II study with correlative endpoints is planned at RP2D. Updated accrual and results will be presented. [Table: see text] [Table: see text]
A phase II study of weekly trabectedin (ET-743) in second/third line ovarian carcinoma
Authors: C. N. Krasner, S. McMeekin, S. Chan, P. Braly, S. Kaye, D. Provencher, J. Klecz, B. Michiels, H. Van de Velde, M. Gore
Journal: Journal of Clinical Oncology (2004)

5045 Background: Trabectedin (Yondelis) is a novel marine-derived agent, binding the minor groove of DNA at nM concentrations and interacting with the transcription-coupled nucleotide excision repair. Activity has been reported in human ovarian cancer with doses scheduled every three weeks (G. Parma et al. ESMO, 2003). Methods: In October '02, a multicenter phase II study in patients with advanced ovarian cancer was initiated, using a weekly schedule of trabectedin (0.58 mg/m2 IV) for three weeks with a week break. Dexamethasone 10 mg was administered 30 min before each infusion. Patients (pts) eligible had to be treated with no more than two prior platinum-containing regimens, with measurable disease (RECIST). According to a two-stage design with Response Rate (RR) as the primary endpoint, 48 pts in platinum-resistant (R) and 52 pts in the sensitive (S) group will be accrued. The study is currently in the second stage. Results: By December 15th '03, 43 R pts and 41 S pts were accrued. For the R group, planned vs. actual dose intensity (RDI) was 86.4 %, with median # previous agents (MA) = 3 [range 2–11]. Two confirmed PRs were observed so far in 27 evaluated pts (> 1 cycle). In the S group, RDI is 90.3%. MA is 2 [range 2–6], 2 PR + 2 CR, both confirmed, were observed so far in 18 evaluated pts (>1 cycle). Overall 26 cycles were delayed, 15 because of drug-related adverse events. The treatment was well tolerated; the main toxicities (grade 3–4) in pooled cycles were: fatigue 10%, liver ALT 7% (reversible), nausea/vomiting 2%, neutropenia 2%. No other notable toxicity (alopecia, mucositis, diarrhea) was observed. Conclusions: This study confirms the activity of trabectedin in ovarian cancer with a well-tolerated weekly schedule. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson PRD, Beerse, Belgium; Johnson & Johnson PRD, Titusville, NJ Johnson & Johnson PRD, Beerse, Belgium; Johnson & Johnson PRD, Titusville, NJ Johnson & Johnson PRD, Beerse, Belgium; Johnson & Johnson PRD, Titusville, NJ Johnson & Johnson
A single institution experience of lung cancer treatment in octogenarians
Authors: S. McCormack, A. Pleister, D. Young, P. Confer, G. A. Otterson
Journal: Journal of Clinical Oncology (2007)

18141 Background: In the NCI’s SEER database nearly 15% of NSCLC patients were = 80 years during the years 1973–2003. As the “elderly” population increases, the percentage of octogenarians with NSCLC will increase. To better understand this population we investigated the patient and tumor characteristics and treatment modalities by stage in octogenarians with NSCLC over a recent 5 year period at The Ohio State University Medical Center. Methods: Patients aged 80 years and older with biopsy-proven NSCLC seen between 1998–2003 were included in the analysis. 74 patients met criteria for study. Data was gathered from the cancer registry and chart reviews. Characteristics included stage, histology, treatment, and co-morbid conditions (pulmonary and non-pulmonary co-morbidities, weight loss, and ECOG PS). PS was either explicitly stated or inferred from the records, or recorded as “unknown” when PS could not be determined. Results: The 74 patients averaged 82.8 years of age (range 80–91), with 53% males and 47% females (83 years of age with 56% males and 44% females from the SEER database). 46% of patients had “surgical” disease (Stage IA, IB, and IIB), 20.3% had stage III disease, 29.7% had stage IV disease, and 4.0% had indeterminate staging. 82.4% of “surgical” disease patients received some variety of treatment (70.6% surgery[S], 23.5% radiation[RT], and 12.5% chemo[Ch]); 80% of stage III patients received treatment (53.3% S, 40% RT, and 33.3% Ch); 50% of stage IV patients received treatment (0% S, 31.8% RT, and 40.9% Ch). Patients with an ECOG PS of 0–1, 2, 3–4, or “unknown” equaled 44.6%, 20.3%, 16.2%, and 18.9% respectively with 81.8%, 100%, 41.7%, and 78.6% of these patients receiving treatment. Conclusions: There is little data on treatment of the ‘extreme elderly.‘ Our analysis of this subset of the elderly reveals that most octogenarians seen at a referral center can receive treatment. The majority of “surgical” disease octogenarians received surgical resection of their primary tumor and the majority of all patients received some treatment. Further studies of outcomes based on staging, co-morbidities, and PS will be important in this population. Additional studies of this population in non-referral centers are of interest. No significant financial relationships to disclose.
Abstract 23: Divergent Temporal Trends in the Incidence of Heart Failure with Preserved and Reduced Ejection Fraction
Authors: Connie W Tsao, Asya Lyass, Martin G Larson, Ramachandran S Vasan
Journal: Circulation (2015)

Background: The past two decades have witnessed divergent trends in the prevalence of major cardiovascular disease risk factors and advances in medical therapy for coronary disease. Over this time period (1990-2009), we hypothesized that the incidence of heart failure with preserved ejection fraction (HFPEF) may have decreased with improved blood pressure control, whereas the incidence of heart failure with reduced ejection fraction (HFREF) may have increased due to improved treatment of coronary disease with myocardial salvage. Methods: We studied Framingham Heart Study Original and Offspring Cohort participants at least 40 years of age and free of HF (n=6648, 56% women, 21285 five-year epochs, 769 HF, 97829 person-years). We estimated age- and sex-adjusted rates of HF, HFPEF, and HFREF (cumulative incidence at 5 years) for 5-year time windows between 1990 and 2009 and for 10-year intervals, 1990-1999 and 2000-2009. We used proportional hazards models to estimate cumulative incidence and test time trends in hazards ratios, for the overall sample and for each sex separately. Results: HF incidence varied modestly across the time windows but differences were not statistically significant overall, in men, or in women ( TABLE ). Across the two decades, there was a 40% increase in the incidence of HFPEF (p=0.003), but a 20% decrease in the incidence of HFREF (p&lt;0.0001). The incidence of HFPEF between decades did not change significantly in men but increased 56% in women (p=0.014). Between decades, the incidence of HFREF declined by 13% in men and by 29% in women (p=0.01 and 0.003, respectively). Conclusions: Whereas the overall incidence of HF has not changed significantly in the past two decades, the incidence of HFPEF has risen and that of HFREF has declined reciprocally, opposite to what we hypothesized. Future investigation into the potential factors underlying these intriguing trends is warranted.
Clinico-pathological and epidemiological study of gallbladder cancer with special reference to gastrointestinal malignancies in Eastern Rajasthan Region
Authors: R. G. Sharma, S. S. Ratnawat, R. Kumar, J. M. Mehta
Journal: Journal of Clinical Oncology (2008)

15662 Background: Carcinoma of the Gall Bladder has a particularly high incidence in Northern India. The present study was undertaken to evaluate the pattern of diseases of gall bladder in reference to overall incidence of gall bladder and GI malignancies in eastern Rajasthan, India. Methods: Study consists of gall bladder disease admitted in general surgery SMS Medical College Jaipur from may, 2003 to feb, 2006. Out of these, there were fifty cases of Ca GB, which were studied. Cancer data from eastern Rajasthan was also scanned to find pattern of GI cancers. Data for cancers was scanned to find the frequencies of various GI cancers in eastern Rajasthan region. Results: A total of 1,499 cases of gall bladder disease were admitted in SMS Medical College Jaipur from may, 2003 to Feb, 2006. Out of these, there were fifty cases of Ca GB, which accounted for 3.3% of all gall bladder diseases. Age above 40 years was affected. Male:Female ratio was 1:2.33. The common presentations were pain abdomen (80%), nausea & vomiting (58%), lump abdomen (52%), fever (46%) and jaundice (40%). Diagnosis of Ca GB rested on USG, CT scan and FNAC. Most common was adenocarcinoma (90%). Majority of the patients were in advanced stage (stage IV 28%, stage Ill 22%, stage II 28%). Majority were treated with palliative measures. Extended cholecystectomy was done in 4% cases. In 16% cases CaGB was found incidentally on pathology after cholecystectomy. 21,868 cases of malignancies were scanned from eastern Rajasthan. GI cancers comprised 3,163 cases. Most common GI cancer was esophagus (29.43%), closely followed by rectum (21.25%), Stomach (14.16%), colon (12.39%), and gall bladder (8.92%). In females carcinoma gall bladder (16.42%) was the third most common malignancy of GI tract and in males carcinoma gall bladder (4.33%) was sixth most common malignancy of GI tract. Conclusions: Ca GB forms the third most common Cancer of GI tract in Eastern Rajasthan. Majority present in advanced stage. 16% of Gall Bladder cancers were found incidentally. High index of suspicion is required to detect the early lesions where adequate surgery can make a difference. No significant financial relationships to disclose.