tbuckley/cabot-search huggingface dataset:
Preoperative clues to guide primary approach in advanced ovarian cancer (OC): The role of CT findings to predict the extent of tumor dissemination.
Authors: G. E. Glaser, M. Torres, B. Kim, G. D. Aletti, A. Weaver, A. Mariani, L. C. Hartmann, W. Cliby
Journal: Journal of Clinical Oncology (2011)

e15541 Background: We previously demonstrated that surgical complexity combined with specific patient factors are key determinants of morbidity in OC treatment. Specifically, high tumor dissemination (HTD) is an important risk factor for poor outcome after primary surgery in medically compromised patients. Thus, reliable preoperative indicators of extent of disease are necessary for considering primary surgery vs. neoadjuvant chemotherapy. We sought to determine whether CT findings could predict extent of disease or surgical complexity in patients with advanced OC. Methods: Preoperative CT scans for patients diagnosed with advanced OC between 1997 and 2003 were retrospectively evaluated for the following rigorously defined findings: ascites; peritoneal thickening; involvement of large bowel, sigmoid colon, spleen, liver, omentum, diaphragm, and lymph nodes. These were compared to the findings at exploration and the surgical procedures performed. Fisher’s Exact test was used to assess correlations. Results: 46 cases met inclusion criteria. Mean age was 66.4 y, mean OR time was 228 min. and 65% had residual disease (RD) 1cm or less. CT findings correlated with positive surgical findings (sensitivity/specificity) as follows: diaphragm disease (48.4%/ 100%); parenchymal liver (100%/93.3%); omental cake (72.4%/64.7%); sigmoid colon (53.9%/100%); ascites (44.4%/100%); large bowel (28.6%/90.9%). When both diaphragm disease and omental cake were present, this predicted HTD(specificity=100%, sensitivity=40%). Additionally, there was strong correlation between CT findings and the corresponding surgical procedures necessary to remove disease: large bowel resection (p=0.079), liver resection (0.087). Conclusions: The findings of diaphragm disease and omental cake on CT scan are highly specific for high tumor dissemination (HTD) at surgical exploration. In addition, multiple CT findings correlate strongly with the need for corresponding high-risk surgical procedures which can be helpful in predicting surgical complexity. This pilot data suggests CT scan may be very useful in preoperative risk-prediction of primary surgical cytoreduction.
Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane.
Authors: Anthony E. Mega, Daniel Peter Petrylak, Philip Kantoff, Joe Stephenson, Nicholas J. Vogelzang, Robert Dreicer, Neal D. Shore, Nancy Stambler, Jennifer Carpenito, Paul D'Ambrosio, Robert Joseph Israel
Journal: Journal of Clinical Oncology (2012)

4662 Background: The abundant expression of prostate specific membrane antigen (PSMA) type II transmembrane glycoprotein on prostate cancer cells provides a rationale for antibody therapy. PSMA ADC, a fully humanized antibody to PSMA linked to the potent antitubulin agent monomethyl auristatin E (MMAE), binds PSMA and is internalized within the prostate cancer cell where cleavage by lysosomal enzymes and releases free MMAE, causing cell cycle arrest and apoptosis. We report results from an ongoing phase 1 dose escalation study of PSMA ADC in subjects with taxane-refractory mCRPC. Methods: Eligibility requirements include progressive mCRPC following taxane-containing chemotherapy and ECOG status of 0 or 1. PSMA ADC was administered by IV infusion Q3W for up to 4 cycles. Adverse events, pharmacokinetics (PK), PSA, circulating tumor cells, clinical disease progression and immunogenic response to PSMA ADC were assessed. Serum PSMA ADC and total antibody were measured by ELISA, and free MMAE was measured by LC/MS/MS.The dosing cohorts range from 0.4 mg/kg to 2.8 mg/kg, with dose escalation continuing. Results: 40 subjects have been dosed in nine dose levels (0.4, 0.7, 1.1, 1.6, 1.8, 2.0, 2.2, 2.5, 2.8 mg/kg). To date, PSMA ADC has been well tolerated with the most commonly seen adverse events being anorexia and nausea, and the most common laboratory abnormalities being reversible hematologic parameters and liver function tests. Antitumor activity has been manifested as reductions either in PSA or circulating tumor cells in the higher dose cohorts. Exposure to PSMA ADC increased with dose and was ~1,000-fold greater than MMAE exposure. Similar PK metrics were observed after the first and third doses. Dosing at the 2.8 mg/kg cohort is continuing and an MTD has not yet been reached. Conclusions: PSMA ADC is generally well tolerated in subjects with mCRPC, previously treated with taxane in doses up to 2.8 mg/kg. Antitumor activity at higher dose levels has been observed. The MTD has not yet been reached and enrollment is ongoing at higher dose levels.
Safety and efficacy during first line with cetuximab in <i>KRAS</i> wild-type metastatic colorectal cancer (mCRC): Results of a large prospective multicenter cohort carried out by the premium French observational study.
Authors: Laurent Mineur, Gilles Seni, Laurent Miglianico, louis-Marie Dourthe, Nathalie Bonichon, Lionel Moreau, Rosine Guimbaud, Denis Smith, Emmanuel Achille, Robert Herve, Jean Michel Bons, Stephane Remy, jean Pierre Daures
Journal: Journal of Clinical Oncology (2013)

555 Background: Cetuximab improves benefit in patients with kras wild type when added to CT for mCRC (Crystal, opus, celim trials). In order to assess the safety and efficacy of cetuximab in daily-practices a national prospective observational multicenter study was performed. Methods: Physicians (n=94), in health institutions (44 public and 46 private hospitals, 4 cancer centers) enrolled prospectively 502 patients. The eligibility criteria were kras wild type mCRC treated with cetuximab in combination with CT as first-line regimen and at least one measurable lesion. Data are available at 3 months, for 496 patients enrolled between september 2009 to march 2012. Results: Mean age 65,7 years old, 62.9% male, ECOG score 0-1 88.1%, 2-3 11.9%, metastases site were liver 70%, lung 26% and others unlimited 39%. Resectable mCCR 10.6%, potentially resectable metastases 33.9% and unresectable 55.5%. Primary tumor location colon: right 20.9%, transverse 6%, left 35.3%, rectum 30.5%, others 7.3%. Primary cancer was resected in 66 % (n=332), 25% (n=125) received adjuvant CT. Cetuximab was administrated respectively every week(20.2%) or two weeks (79.8% of patients). CT regimens were folfiri 51.8%, folfox 4 36.5%, others 11.7%. At 3 months response rate was complete in 4.6%, partial 44.9%, stable 34%, progression disease 16.5%. Reasons for specific cetuximab treatment discontinuation (n=207) were progressive disease 35.3%, therapeutic break 23.2%, all grade cutaneous toxicity and allergic reaction 15.9%, patient request 2.9%, surgery recruitment 20% radiotherapy, radiofrequency and others 2.7%. Adverse events in grade 2 and 3-4 were respectively neutropenia (9.4%;7.9%), anemia (8.5%;1.4%), thrombocytopenia (2.6%;1%), diarrhea (10.8%;5.3%) vomiting (5.3%;2.2%), folliculitis (17.9%;3%), xerosis (13.3%;2%), paronychia (5%;0.9%), allergy 3.4%. Conclusions: Values reported are consistent with those previously identified trials and can better understand the reasons of drug stopping. The study continues to evaluate prognostic factors influencing response, toxicity and drug discontinuation.
An analysis of serum heparan sulfate concentration and EGFR tyrosine kinase inhibitor treatment in patients with non-small cell lung adenocarcinoma.
Authors: M. Nishio, T. Yamanaka, K. Matsumoto, H. Kimura, K. Sakai, A. Sakai, T. Sone, A. Horiike, F. Koizumi, K. Kasahara, T. Ohira, N. Ikeda, N. Saijo, T. Arao, K. Nishio
Journal: Journal of Clinical Oncology (2011)

10601 Background: The EGFR mutation status is a validated biomarker for the stratification of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatment in patients with non-small-cell lung cancer (NSCLC); however, its use is limited in patients with wild-type EGFR, and new biomarkers are needed. We hypothesized that the serum concentration of heparan sulfate (HS), which activates oncogenic growth factor receptor signaling through EGFR and non-EGFR signaling pathways, may be a novel glycobiological biomarker for EGFR-TKIs treatment in NSCLC. Methods: The pre-treatment serum HS concentrations were determined using ELISA in 83 patients with stage IV non-small-cell lung adenocarcinoma who received EGFR-TKIs treatment. The relationship between the serum HS concentrations and patient characteristics, tumor response, progression-free survival (PFS) and overall survival (OS) were analyzed. Results: Patient sex, performance status, smoking history, and EGFR mutation status were associated with tumor response. The serum HS concentrations were significantly higher among patients with progressive disease (PD) than among those without PD (P=0.003). Furthermore, the serum HS concentrations were strongly associated with a poor PFS and OS in a univariate Cox analysis (P=0.0022 and P=0.0003, respectively). A stratified multivariate Cox model according to the EGFR mutation status showed that higher HS concentrations were significantly associated with a shorter PFS and OS (P=0.0012 and P=0.0003). Conclusions: We concluded that a high serum HS concentration was strongly related to a poor treatment outcome of EGFR-TKIs and may be a promising non-invasive and repeatable glycobiological biomarker in cancer treatment.
Epithelial-mesenchymal transition in patients with HER2+ metastatic breast cancer.
Authors: A. Giordano, M. Mego, B. Lee, S. Anfossi, C. A. Parker, R. H. Alvarez, N. T. Ueno, V. Valero, M. Cristofanilli, J. M. Reuben
Journal: Journal of Clinical Oncology (2011)

623 Background: The detection of ≥ 5 CTCs by CellSearch in women with metastatic breast cancer (MBC) is predictive of early recurrence and poor survival. Whereas CTC enumeration appears to be predictive of response in hormone receptor-positive and triple-negative breast cancers, it is least predictive in HER2+ cancers treated with targeted therapy suggesting an interaction with such therapies. A potential explanation for this discrepancy is the possible loss of epithelial differentiation and the acquisition of epithelial-mesenchymal transition (EMT). Thus, we assessed CTC gene profile in HER2+ MBC for transcription factors (TF) known to induce EMT. Methods: Between August 2009 and March 2010, HER2+ MBC patients (pts) had baseline assessment before starting a new treatment. Seventeen pts (A) provided > 3x107 peripheral blood mononuclear cells (PBMC) and 13 pts (B) provided fewer PBMC. PBMC of A were enriched for epithelial cells (CD326+) and the residual PBMC were depleted of leukocytes (CD326-CD45-). PBMC of B were separated into leukocyte enriched (CD45+) and leukocyte-depleted (CD45-) fractions. All cell enrichments and depletions were performed using antibody-coated magnetic bead separation techniques and AutoMACSPro Cell Separator (Miltenyi-Biotec, Auburn, CA). RNA extracted from all cell fractions was reverse transcribed to cDNA and subjected to qRT-PCR to detect the EMT-inducing TF (TWIST1, SNAIL1, ZEB1, TG2) and HER2 using the TaqMan RNA Assays (Applied Biosystems, Foster City, CA). Concurrently, 7.5 mL of blood from 19 pts were collected for CTC enumeration by CellSearch. Results: Of the 30 pts studied, 28 were HER2+ and 10 pts received a first-line treatment with trastuzumab. The CD326+ cell fractions of A had at least 1 EMT-inducing TF amplified in 14/17 pts. In the CD45- cell fractions (A+B), EMT-inducing TF were amplified in 18/29 pts. Eight of 16 pts (50%) with < 5 CTCs in the blood at CellSearch demonstrated EMT+ cells. Conclusions: Our data indicate that HER2+ MBC pts had CD326+ as well as CD326-CD45- cells that exhibited EMT characteristics suggesting that some of the CTC may be in partial EMT. Additional study is warranted to determine if EMT events have prognostic value in HER2+ pts treated with targeted therapies.
Organizational factors influencing specialty palliative care utilization at academic cancer centers.
Authors: Yael Schenker, Michael W. Rabow, Megan Crowley-Makota, Mallory Marie Waters, Michelle Nkumsah, Douglas B White, Edward Chu, Cardinale B. Smith, Robert Arnold
Journal: Journal of Clinical Oncology (2016)

109 Background: Rates of early specialty palliative care utilization remain low, despite increasing familiarity and favorable attitudes amongst cancer center oncologists. In this context, understanding organizational barriers to specialty palliative care use becomes critical. Methods: We conducted a qualitative interview study with 74 medical oncologists practicing at 3 U.S. academic cancer centers with well-established specialty palliative care clinics. The in-depth interview guide elicited experiences and views related to outpatient palliative care. For this analysis, we focused on organizational factors influencing palliative care use, defined as the structural arrangements and social patterns that facilitate or impede implementation of best practices in healthcare. The team conducted mixed deductive and inductive coding, using Cabana’s quality improvement framework as a starting point. Key concepts were iteratively refined with interdisciplinary input. Two coders applied the final codebook to all transcripts, with disagreements reviewed and resolved by team consensus. Results: Participating oncologists were 68% male, specialized in solid tumors (61%), hematologic malignancies (32%), or both (7%), and had been practicing oncology for a mean of 17 (SD 12) years. Organizational factors impeding early specialty palliative care utilization included: the perceived burden on patients from spending more time at clinic appointments, which was balanced against the value added from specialty palliative care; social, financial, and disease-related factors interfering with patients’ ability to attend additional specialty visits; the clinic name, with concern that patients equated ‘palliative care’ with death, dying or giving up; an unwieldy referral process without availability of same-day appointments; and inadequate communication between oncologists and palliative care specialists. Conclusions: Even when oncologists are aware of the evidence and agree with recommended practices, organizational factors may impede adherence to oncologic and palliative care guidelines. Addressing these barriers could improve use of outpatient specialty palliative care.
Activity and toxicity of pegylated liposomal doxorubicin in combination regimen (DRCOP) for patients &gt;60 years old with untreated diffuse large B cell lymphoma (DLBCL): A phase II study
Authors: M. A. Rodriguez, M. Fanale, F. B. Hagemeister, P. McLaughlin, B. Pro, J. E. Romaguera, L. Kwak, L. E. Fayad, J. Durand
Journal: Journal of Clinical Oncology (2008)

20505 Background: DLBCL is a common lymphoma of older adults, and a potentially curable disorder with the regimen RCHOP (Coiffier, et. Al. NEJM, 2002). Doxorubicin, a key drug in the regimen, has risk for cardiotoxicity, and thus of concern in older patients (pts) with higher incidence of cardiovascular (CV) disease. In breast cancer pts pegylated liposomal doxorubicin (D) has shown greater cardiac safety and similar efficacy to doxorubicin. We thus replaced doxorubicin with D in RCHOP (DRCOP). Methods: The regimen is: Rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1- 5. Eligibility criteria are: >60 years of age; untreated confirmed DLBCL (no discordant histology); Ann Arbor stage II-IV; baseline LVEF 50%. CV disease is permitted, if symptoms controlled, but consult at baseline by Cardiologist and at follow-up is required. Growth factor support recommended (not required). Results: 46 pts have been enrolled on study, and are evaluable for toxicity; 36 evaluable for response (1 pt off study after 1 cycle; 7 too early for response). Characteristics of pts: age 61–92 (median 75); 23 female; IPI 1=3 pt; IPI 2=3 pts; IPI ≥3=40 pts. Responses are 34/36 (94%) CR; 2/36 (6%) PR. At this time, 5/32 died: (3 progression; 1 death due to non-neutropenic pneumonia; 1 death due to unrelated disease). Grade 3–4 adverse events were: 1 drop in LVEF; 8 atrial arrhythmias (reversed); 1 hypotension (reversed); 1 chest pain (reversed); 18 neutropenia (13 febrile, with 5 infections); 3 hand-foot syndrome; 4 fatigue; 2 DVT; 2 neuropathy. Conclusions: The CR rate of DRCOP in this study is 94%, which is remarkable given most pts have had intermediate/high risk IPI. Despite advanced age and cardiac comorbidities, we’ve noted only one case of low LVEF; more common are atrial arrhythmias (8 pts), reversible. Pegylated liposomal doxorubicin merits consideration for treatment of lymphomas in older adults. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ortho Biotech
Long-term survival of EMR-PDT for gastric cancer.
Authors: Hiroyuki Narahara, Kaori Morita, Kayo Yasuda, Kenji Aoi, Miki Saita, Seriko Ikezoe, Kazunori Yanagawa, Eriko Masuda, Juichi Fukushima, Hitoshi Matsumoto, Yuichi Yasunaga, Yoshiaki Inui, Sumio Kawata, Koji Higashino
Journal: Journal of Clinical Oncology (2013)

85 Background: Some patients and their family refuse to undergo the surgical operation because of age or complicated diseases. Endoscopic mucosal resection (EMR) technique is popular in Japan. This method has the advantage of a histologic examination, but its uses are limited to mucosal lesions and a part of submucosal lesions (sm1). For early gastric cancer, we treated patients by photodynamic therapy (PDT) in combination with EMR (that is EMR-PDT). Methods: We treated twenty-five patients with gastric cancer by EMR-PDT from April, 1997 till March, 2004. The median age was 79 (56-88) years old. All the patients were diagnosed that it is impossible to undergo a surgical operation due to their age or complicated diseases. The endoscopic ultrasonography (EUS) showed massive invasion of the submucosal layer in sixteen cancer lesions and the muscularis propria in nine cancer lesions.In order to reduce the tumor size, piecemeal snarectomy (EMR) is performed. One week later, PDT is performed. After the intravenous injection of 2 mg/kg of Photofrin, the excimer dye laser (EDL) at 630 nm is irradiated transmitted endoscopically. The energy intensity is over 60 J/cm 2 . Results: 1. Early gastric cancer (sm massive): as for complications, two patients showed pyloric stenosis after treatment but both of them were cured successfully by endoscopic treatment. As for local response, 15 out of 16 patients showed cure completely. From a viewpoint of long-term outcome, during the observation period of five years (from one year to 11 years), nine patients died and six patients are alive. Only one patint died of gastric cancer four years later, and other eight patients died from other causes. The longest cancer survivor is still alive after 11 years after EMR-PDT with no recurrence of cancer. Disease-specific survival is 93%. Three- year survival rate is 85%. 2. Advanced cancer: Any of the patient were not alive more than three years. 3. Regardless of their advanced age and complications, such as liver dysfunction and renal dysfunctions, both PDT and EMR-PDT showed extremely high safety. No treatment related death was observed. Conclusions: EMR-PDT is a promising method for early gastric cancer because of its safety and long-term good outcome.
Preliminary quality-of-life outcomes for SWOG-9346: Intermittent androgen deprivation in patients with hormone-sensitive metastatic prostate cancer (HSM1PC)—Phase III.
Authors: Carol Moinpour, Donna Lynn Berry, Benjamin Ely, Catherine M. Tangen, Celestia S. Higano, Joel Picus, Paul F. Schellhammer, Eila C. Skinner, Michael L. Cher, Ian Murchie Thompson, Maha Hussain
Journal: Journal of Clinical Oncology (2012)

4571 Background: The relative quality of life (QOL) for patients with newly diagnosed, metastatic prostate cancer, treated with intermittent androgen deprivation (IAD) has been assumed and hypothesized, yet never compared in a well-powered randomized trial (RT) to continuous androgen deprivation (CAD). SWOG-9346 provided such a RT in which to test QOL differences between CAD and IAD in men with metastatic prostate cancer. Methods: Patients were randomized to CAD or IAD. Patients completed the SWOG QOL Questionnaire (SF-20/SF-36, Symptom Distress Scale, treatment-specific symptoms, global QOL) at randomization and months (mo) 3, 9, and 15 post-randomization. Five QOL change scores at one time point (mo 3) were designated as primary for the QOL endpoint and are reported in this abstract: impotence, libido, energy/vitality (E/V), physical function (PF), and emotional function (EF). Significance level was adjusted for 5 comparisons (used p=0.01). Results: 615 patients in the CAD arm and 633 in the IAD arm completed the QOL questionnaire at baseline. Change between baseline and 3 months differed for the two arms with CAD reporting statistically significantly more impotence and less libido than IAD. EF was also slightly better for the IAD arm. Conclusions: These results indicate better sexual function in men receiving IAD versus CAD through post-randomization month 3. Additional benefits for IAD may include better PF, E/V and EF. Ongoing analyses will address the role of missing data, additional follow-up assessments, and resumption of therapy in the IAD arm. [Table: see text]
Does 18-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) predict survival in advanced pancreatic cancer? A single-institution experience.
Authors: Noman Ashraf, Saqib Razzaque, Jill M. Weber, Mokenge Peter Malafa, Richard D. Kim
Journal: Journal of Clinical Oncology (2012)

e14715 Background: Pancreatic cancer is associated with a poor prognosis. Histological grade, stage and serum tumor markers are well established prognostic factors for survival. Some studies suggest that 18-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) correlates with survival in pancreatic cancer. In this study, we aimed to determine whether standardized uptake value (SUV), a measure of FDG uptake by fusion PET/CT, had prognostic significance in patients with advanced pancreatic cancer. Methods: Using a comprehensive pancreatic cancer database at H. Lee Moffitt Cancer Center, we identified patients who underwent PET/CT scan as initial workup for resection but were found to have advanced disease (stages III and IV) when surgery was attempted. Data from January 2006 to December 2010 was retrospectively analyzed and correlated with the maximum SUV determined by PET/CT. Other prognostic factors including stage, age, gender, serum tumor marker CA 19-9 levels and the use of chemotherapy were also evaluated using multivariate analysis. Results: We identified 41 consecutive patients who were deemed resectable by virtue of staging workup with CT, PET/CT and endoscopic ultrasound (EUS), but found to have locally advanced/metastatic disease intra-operatively. At the time of analysis, there were a total of 30 deaths. Twelve patients had metastatic disease and 29 had stage III pancreatic cancer. SUV uptake ranged from 2.9 to 16.2 with a mean of 6.4. Median overall survival for the 28 patients with SUV less than or equal to the mean (≤ 6.4) was 14 months (95% confidence interval 10 – 25 months) vs. 9.1 months for the 13 patients with SUV &gt; 6.4 (95% confidence interval 4-17 months). This difference was not statistically significant (p=0.178). On multivariate analysis, use of chemotherapy was the only independent predictor of survival. Conclusions: Glucose uptake by PET/CT, reflected by SUV, was not found to be a predictor of survival in patients with advanced pancreatic cancer. The retrospective nature and limited sample size are limitations of our study, however further research is warranted.