tbuckley/cabot-search huggingface dataset:
Optimal management of emergent hypertension during treatment with a VEGF signaling inhibitor: A randomized phase II study of cediranib
Authors: M. Langenberg, C. M. van Herpen, J. S. De Bono, C. Unger, J. H. Schellens, K. Hoekman, H. E. Blum, F. Le Maulf, A. Fielding, E. E. Voest
Journal: Journal of Clinical Oncology (2008)

3555 Background: Hypertension (HT) is a commonly reported side effect following administration of agents that target VEGF signaling. Cediranib (AZD2171) is an oral, highly potent and selective inhibitor of VEGF signaling, with activity against VEGFR-1, -2 and -3. This study prospectively investigated the optimal HT management approach to minimize dose interruptions and reductions in order to maximize cediranib dose intensity. Methods: Patients with advanced solid tumors (n=126) were randomized to one of four treatment groups: cediranib 30 or 45 mg/day ± antihypertensive prophylaxis. The prophylaxis groups received a low dose of calcium channel antagonist (CCA) 3–7 days before starting cediranib. All patients received standardized, predefined HT management commencing with a CCA followed, when needed, by a beta blocker and/or an ACE inhibitor. Results: Cediranib was generally well tolerated and all groups achieved high dose intensities in the 12 week assessment period (88–89%, 30 mg; 74–79%, 45 mg). Increases in blood pressure (BP) were evident early during treatment, and patients with pre-existing HT (ie, receiving antihypertensive therapy before study entry) appeared to be at a greater risk of moderate/severe HT. Only 1 patient developed severe HT in the groups receiving prophylaxis compared to 18 patients in the non-prophylaxis groups. Prophylaxis did not result in less dose reductions or interruptions. Overall 67% of patients entered the HT management plan during the study, with most (∼90%) entered by day 21. In all arms, the adverse event profile and steady-state pharmacokinetic (PK) parameters were similar to other single-agent studies with cediranib. There was no clear relationship between any steady-state PK parameter and maximal changes in BP. There were 9 partial responses across the four groups. Conclusions: This is the first prospectively randomized study to investigate HT management with an inhibitor of VEGF signaling. Prophylactic treatment with antihypertensives did not reduce dose interruptions. However, early recognition and treatment of HT is likely to reduce the number of severe HT events. The current plan for managing HT appeared to be effective compared with previous studies where no plan was in place. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca
Value metrics of a nurse navigator patient support program within a multidisciplinary esophageal cancer clinic.
Authors: Helen J. Ross, Joy Freese, Denise Ciafone, Jonathan Ben Ashman, William G. Rule, Dawn E. Jaroszewski, Kristi L. Harold, Harshita Paripati, Michael Crowell, Rahul Pannala, Douglas Faigel, Francisco Ramirez, Robert Bright, David Fleischer
Journal: Journal of Clinical Oncology (2012)

158 Background: Esophageal cancer patients (pts) require multidisciplinary management involving thoracic and general surgeons, medical and radiation oncologists, gastroenterologists and psychiatrists. Pts navigate complex medical discussions and endure challenges to nutrition, body image, swallowing mechanics, energy level and weight, mood, and performance status. Coordination of care is complicated by multiple sites of pt entry, complex scheduling requirements, and incomplete information at multidisciplinary consultation. A nurse navigator to coordinate the patient experience may optimize treatment and improve outcomes, quality of life and patient satisfaction. Methods: The nurse navigator evaluates all pt records prior to initial appointment and coordinates scheduling, records acquisition, testing and specialty appointments. The nurse navigator serves as a liaison with pts throughout the course of care and provides a patient navigation book (PNB) as a central source for patient-directed information and record keeping. Benchmarks compared before and after creation of the nurse navigator position include: (1) time from appointment request to multidisciplinary evaluation and start of treatment; (2) completeness of medical records and data (scans, pathology slides); (3) patient awareness of support services for themselves and caregivers; (4) utilization of the PNB; (5) number and frequency of interim hospitalizations and emergency room visits; (6) patient, caregiver, and physician satisfaction. Results: From January to July 2012, 27 gastroesophageal cancer pts have been followed by the nurse navigator. Most of these patients remain on active treatment, hence benchmark analysis is ongoing. Metrics thus far suggest improvement in time to treatment start and awareness of patient resources, use of the PNB and patient satisfaction. Conclusions: Esophageal cancer pts undergo complex and toxic multimodality therapy with curative intent. A dedicated nurse navigator may improve the patient experience, optimize adherence to guideline based therapy and appropriate timeframes and provide continuity to pts undergoing multidisciplinary treatment.
Does age matter in pancreatic resection?
Authors: L. C. Connell, E. Mulvihill, M. O'Keeffe, C. O Suilleabhain, S. O'Reilly, D. G. Power
Journal: Journal of Clinical Oncology (2011)

e19689 Background: Surgery offers the only potential for cure in localized pancreatic cancer and most patients (pts) are >65 years (yrs) at diagnosis. Due to compromised physiological reserve, co-morbidities and the natural history of pancreatic cancer, elderly pts are often denied surgical resection. We assessed our institution’s experience of pancreatic resection for pts ≥ 70 yrs. Methods: A prospectively maintained institutional database was retrospectively reviewed for all pts undergoing pancreatic resection from 2006 to 2010. Demographics, laboratory, treatment and outcomes data were obtained. Results: Of 62 pts who had surgery for pancreatic neoplasm, 18 (29%) pts were ≥ 70 yrs. Sites of disease in these pts were pancreas head (n=11,61%), ampullary(n=4,22%), and distal cholangiocarcinoma (n=3, 17%). Surgical procedures were pancreaticoduodenectomy (n=15, 83%) and double biliary bypass (n=3, 17%) [due to occult metastases at surgery]. Pathologies were adenocarcinoma [AC] (n=15,83%) and NET/IPMN (n=3, 17%). Number of R0 resections was 14 (14/15, 93%), with positive lymph nodes in most cases.Pre-operative comorbidities included: COPD (n=3, 17%), and vascular disease (n=10, 55%). Median baseline ECOG was 1 (range, 0-2). Significant post-operative morbidities were aspiration pneumonia (n=1, 5%), heart block (n=1, 5%) and biliary leak (n=3, 17%). There was no perioperative mortality. Median length of hospital stay was 13 days (range, 9-50). The majority of pts were referred to medical oncology with complete recovery of baseline ECOG. Twelve pts who underwent pancreatico-duodenectomy for AC (80%) received adjuvant chemotherapy (with expected toxicities) and the remaining 3 pts required no treatment. No pts were lost to follow-up. Ten pts, after pancreatico-duodenectomy and adjuvant therapy had at least 2 yrs follow-up with median overall survival of 21.1 months (range, 12-44). Conclusions: Therapeutic nihilism exists in the treatment of pancreas cancer in elderly pts. This group can undergo pancreatic resection with acceptable morbidity, mortality and overall outcome as is evidenced in our experience. Standard pre-operative assessment and geriatric scoring systems along with better post-operative care should allow optimal oncologic treatment in older pts.
Impact of chemotherapy and radiation therapy on local control and survival of metastatic breast cancer to the brain: Single-institution review of 792 cases.
Authors: Diogo Bugano Diniz Gomes, Rita Elias Deeba, Vicente Valero, Stacy L. Moulder, Banu Arun, Ricardo H. Alvarez, Limin Hsu, Nuhad K. Ibrahim
Journal: Journal of Clinical Oncology (2014)

146 Background: There are various treatment modalities for metastatic breast cancer to the brain (MBC-b), with wide variation of reported outcomes. Methods: There were 1,513 patients (pts) with MBC-b treated at MD Anderson Cancer Center October 2009-December 2012. We reviewed medical records of the first consecutive 1015 and included 792 with confirmed brain metastases (BM). A Cox multivariate model was used to identify the effect of treatment on time-to-progression in the brain (TTP-b) and overall survival (OS). Results: Disease subtypes: ER+/HER2- (27%); ER+/HER2+ (16%); ER-/HER2+ (18%); ER-/HER2- (29%), missing (10%). Number of BM: 1 (20%), &gt;1 (73%), missing (7%). Local treatment: metastasectomy (S) (13%), radio-surgery (SRS) (12%), whole-brain radiation (WBRT) (57%), combination of S/SRS with WBRT (11%), no treatment (7%). Systemic treatment: Any (64%), HER2 directed (24%). Median OS was 11.33 months(m) (4.4-25.8). Clinical characteristics associated with OS in multivariate analysis: ER+, HER2+, age &lt; 60, ECOG 0-1, single BM, controlled systemic disease at time of BM and &lt;3 treatment lines before BM. After correction for covariates, use of systemic therapy was associated with longer OS (HR 0.35 CI 0.20-0.60, p &lt; 0.001) regardless of subgroup: HER2+ (19.9 vs 3.5m), ER+/HER2- (12.7 vs 2.2m), ER-/HER- (10.5 vs 2.3m). In pts receiving trastuzumab at diagnosis of BM, continuation of HER2 therapy increased OS (HR 0.44 CI 0.25-0.77, p = 0.004) regardless of agent used (lapatinib vs trastuzumab p=0.7). OS was the same for S and SRS (p=0.7) and either one increased OS (HR 0.41 CI 0.21-0.79 p=0.008). WBRT prolonged OS in multiple BM (HR 0.61 CI 0.38-0.96); Median TTP-b was 11.07m (5-24). WBRT added to S/SRS had longer TTP-b than either modality alone (17.6m vs 10.4m HR 0.56 CI 0.37-0.85 p=0.006). Use of systemic therapy after diagnosis of BM increased TTP-b (11.8 vs 5.1m HR 0.55 CI 0.33-0.92 p = 0.024), but there was no difference between agents used (lapatininib vs trastuzumab p=0.79; capecitabine vs others p= 0.96). Conclusions: WBRT improved local control when done after S/SRS. The use of chemotherapy after local therapy improved time to progression in the brain and survival.
Surgical resection in early limited-stage small cell lung cancer: Time to rethink? A retrospective analysis of the VA Central Cancer Registry.
Authors: T. Tashi, I. T. Aldoss, W. Gonsalves, A. K. Ganti, P. T. Silberstein, P. Townley, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

7021 Background: Concurrent chemoradiation is the standard of care for limited stage small cell lung cancer (L-SCLC). However, few reports suggest a survival benefit for surgical resection. Our objective is to analyze the outcomes of surgical resection for patients with L-SCLC. Methods: 8791 patients diagnosed with L-SCLC between 1995 and 2008, were identified from the VA Central Cancer Registry. These patients were then grouped according to age, sex, race, stage, grade and type of treatment received. Kaplan-Meier survival method and Cox proportional hazards model were used for analysis. Results: Out of 8,791 patients with L-SCLC, 915 (10.4%) had undergone surgical resection, while 5,865 (66.6%) received chemotherapy alone, radiation therapy alone or combination of both and 2011 (22.9%) received no treatment. Of the 915 patients who had surgery, 65.8% were stage 1, 13.4% stage 2 and 20.8% stage 3. Lobectomy with LN dissection was the most common surgical procedure performed in 424 (46.3%) of the patients, followed by local excision in 193 (21.1%), simple lobectomy in 188 (20.5%) and 64 (6.9%) had pneumonectomy. Surgery was associated with improved median survival across all stages as compared to non-surgical treatments, 45.9 vs 15.9 months in stage 1, 39.4 vs 13.7 months in stage 2 and 21.8 vs 11.5 months in stage 3 (p<0.0001). Of the 915 surgical patients, 561 (61.3%) had surgery only and their median OS was 44.4 months while 354 (38.7%) had surgery followed by adjuvant treatment and their median OS was 32.3 months (p=0.069). Survival was significantly better in those who received chemoradiation following surgery compared to chemoradiation alone (30.9 vs 14.7 months, p<0.0001). Across the entire cohort, median OS was 38.7 months in surgical group and 12.4 months in the non-surgical group (p<0.0001). Age, race, stage, tumor grade, tobacco use and treatment modality are significant variables for survival. Conclusions: Patients with L-SCLC who underwent surgical resection have improved median survival across all stages. Surgery could be potentially considered in early stage patients. However, further prospective trials are warranted to evaluate its role in treatment of L-SCLC.
ATTAX2: Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophago-gastric cancer—Final results of a multicentre phase II trial by the AGITG
Authors: N. C. Tebbutt, T. Sourjina, A. H. Strickland, G. A. Van Hazel, N. Pavlakis, V. Ganju, C. Murone, D. MacGregor, V. Gebski, M. Cummins
Journal: Journal of Clinical Oncology (2008)

15554 Background: Chemotherapy-refractory oesophago-gastric (OG) cancer has a very poor prognosis. Cetuximab can reverse chemotherapy resistance and preclinical data show synergy between cetuximab and docetaxel. This study evaluated the efficacy and safety of the combination of docetaxel and cetuximab as second-line treatment in docetaxel-refractory OG cancer. Methods: Eligibility criteria included histologically confirmed, metastatic OG carcinoma, measurable disease, PS0–2, adequate organ function, disease progression within 6 months of first-line docetaxel therapy, informed consent. Recruitment was initially restricted to tumours with epidermal growth factor receptor (EGFR) detectable by immunohistochemistry, with a subsequent amendment allowing tumours of any EGFR status. Patients (Pts) received docetaxel 30mg/m2 d1 and d8 q3w and cetuximab initial 400mg/m2, then 250 mg/m2 weekly. The primary endpoint was confirmed response rate (RR) using RECIST criteria. A Simon 2-stage design was used, with 2/17 responses required in the first stage to allow continuation to 35 pts. Results: Accrual of 38 pts was completed in February 2007. Pt characteristics were: median age 61 yrs (range 36−80); PS 0/1/2 (%), 39/55/5; ≥2 involved organ sites, 82%; liver metastases, 63%; peritoneal metastases, 11%; EGFR detectable, 79%. Median time from last docetaxel treatment until disease progression was 0.7 mo. Main grade 3/4 toxicities in 38 evaluable pts were febrile neutropenia (3%), anorexia (16%), nausea (8%), diarrhoea (11%), stomatitis (3%), acneiform rash (5%). The 60-day all-cause mortality rate was 15.8% (95% CI: 7–30), with no treatment-related deaths. In 35 evaluable pts, response rates (95% CI) were: PR, 6% (1.6–18.6); SD, 43% (28–59). With a median follow up of 19 mo, median progression-free (PFS) and overall survival (OS) times were 2.1 mo and 5.3 mo, respectively. A landmark analysis showed a clear trend to improved PFS and OS times, with an increased grade of acneiform rash. Conclusions: Cetuximab and docetaxel achieved modest responses rates, but maintained PFS and OS times comparable with other salvage regimens in refractory OG cancer, with low rates of toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck, sanofi-aventis
Gene expression profiling of paraffin embedded melanoma specimens
Authors: E. D. Whitman, M. Moore, D. Baunoch
Journal: Journal of Clinical Oncology (2005)

7532 Background: Melanoma patients exhibit a wide variety of clinical outcomes not well predicted by their clinical or pathologic stage. Genetic profiling with gene chip microarrays potentially distinguish melanoma from other malignancies, suggest genetic-level relationships to other cancers, and may sub-classify melanoma cases by prognosis and outcome. Implementation of this technology has previously been limited by the need for fresh or fresh-frozen tissue, but new developments now allow the examination of paraffin embedded specimens (PES). In this study, archival melanoma PES were used to build a diagnostic gene chip “bank” and analyzed for significant gene over- and under- expression as well as mathematical relationships to other tumor types. Methods: As part of an overall tumor of unknown origin project, archival PES from melanoma patients, among multiple other tumor types (550 cases of over 60 tumor types, including 12 melanomas, 12 basal cell carcinomas and 8 squamous cell carcinomas), were used to create messenger RNA and then hybridized to a custom 22,000 gene expression microarray (Agilent Technologies). Results were analyzed with GeneMaths image analysis software (Applied-Math, Sint-Martens-Latem, Belgium), identifying genes over- and under- expressed beyond 2 standard deviations away from the mean expression for each gene. Results: Gene expression profiling was used to identify a gene expression signature capable of differentiating melanoma cases from over 60 tumor types, even in a metastatic setting. Over 30 genes were identified that were predominately over expressed only in melanoma tumors. Conclusions: Genetic profiling of archival PES from melanoma patients gives reproducible results identifying genes relatively over- and under- expressed. Further studies are planned to elucidate the role that these genes play in melanoma tumor progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration US Labs
Characteristics of multiple primary tumours (MPT) in patients with family history of cancer
Authors: V. D. Petrova, A. F. Lazarev, S. A. Terekhova, N. A. Zarubina, E. L. Sekerzhinskaya, T. V. Sinkina
Journal: Journal of Clinical Oncology (2008)

22133 Background: Many investigators consider MPT typical for patients from families with cancer history, but the characteristics of polyneoplasia in this group of patients are still to be analyzed. Methods: The registry of patients from “cancer”-families (who had 3 and more relatives by blood with cancers), formed in Altai oncological centre, included 1986 patients (196 male and 1790 female) ages 28 to 74. All of them were kept under medical observation according to in-house designed algorithms. MPT in this group were analyzed as compared to general population of the Altai territory (the data of the Altai territory cancer registry). Results: MPT were registered in 28 patients (27 female and 1 male) from “cancer”-families (all in early stages). The proportion of patients with MPC in this group was significantly higher (1.4%) than in general population (0.66%). The average age of the patients at the moment of first cancer revealing (47.6 years) was significantly lower than the same in general population (59.7 years). In the group of patients from “cancer”-families with MPT there were more patients in younger ages as compared to the same in general population: at the age before 29 - 3.6% and 2.6%, respectively; 30–39 years old - 21.4% and 4.1%, respectively; 40–49 years old - 32.1% and 13.8%, respectively. 4 patients from “cancer”-families had synchronous MPT, 24 - metachronous. The mean interval between the first and the second cancer was 6,6 years. Combinations of the tumours of reproductive system (breast, ovarian cancer, cancer of cervix and corpus uteri) and thyroid cancer were the most frequent. Conclusion: In the group of patients from “cancer”-families MPT were registered more often, than in general population and in younger ages. Patients with MPT from this group most often had cancers of reproductive system. Medical observation of this group of patients organized in proper way made it possible to predict and reveal cancers in early stages. No significant financial relationships to disclose.
Cytotoxic therapy beyond second line in non-small cell lung cancer: Patterns of care and survival.
Authors: S. Sheth, J. R. Hoverman, B. Turnwald
Journal: Journal of Clinical Oncology (2010)

e16562 Background: Third-line and greater cytotoxic treatment has been poorly studied in patients with advanced non-small cell lung cancer (NSCLC). To date, there is no third-line cytotoxic treatment that is considered standard of care. Therefore, limited clinical data suggest survival benefit for third-line cytotoxic treatment and beyond. This retrospective study reports the patterns of care and outcomes for third-line and greater cytotoxic treatment in NSCLC. Methods: Anelectronic health record (iKnowMed) from 27 outpatient community cancer centers were reviewed. NSCLC patients with documented > third-line cytotoxic treatment between June 1, 2006 to March 30, 2009 were identified and followed through October 2009. Cytotoxic treatment, time to next line of therapy, and survival were evaluated. Patients were excluded if there was history of clinical trial, had received erlotinib, and/or insufficient data. Results: 1,027 of 8,873 patients received third-line cytotoxic therapy or greater (median age 64; 45% female). 7846 of 8,873 patients did not receive therapy beyond third line (median age 67; 43% female). 763 of 1,027 patients received third-line (median age 63; 44% female), 297 of 1,027 patients received fourth line, 110 of 1,027 patients received fifth line, and 43 patients received sixth line. Common cytotoxic treaments administered third to sixth line were: pemetrexed (10%-28%), docetaxel (11%-15%), vinorelbine (12%-16%), and gemcitabine (13%-15%). Median time to next line of therapy was 137 days from third to fourth line, 106 days from fourth to fifth line, and 86 days from fifth to sixth line. Median overall survival for patients receiving third-line cytotoxic treatment and greater compared to best supportive care was 25 months vs. 8 months, respectively (p < 0.0001; HR 2.13 [95% CI: 1.94 to 2.35]). Conclusions: The wide array of cytotoxic treatment utilized third- line and beyond illustrates no standard pattern in selection of therapy. This study identified a small group of remarkably long-lived survivors that skew the survival curves with each subsequent line of therapy. The association of this survival with chemotherapy requires more detailed evaluation. No significant financial relationships to disclose.
Modulation of Soluble Interleukin 2 Receptor (sIL-2R) Levels in Patients with HIVWaldenstrom Macroglobulinemia (HIV-WM) Treated with Biaxin-Pentoxifylline-Dexamethasone Followed by Prednisolone (BPD-Pred)
Authors: Eugene McPherson, P. Tassy
Journal: Blood (2008)