tbuckley/cabot-search huggingface dataset:
A unified prognostic model for first- and second-line targeted therapy in metastatic renal cell carcinoma (mRCC): Results from a large international study.
Authors: D. Y. Heng, W. Xie, G. A. Bjarnason, U. N. Vaishampayan, F. Donskov, L. Wood, J. J. Knox, M. Tan, C. K. Kollmannsberger, B. I. Rini, T. K. Choueiri
Journal: Journal of Clinical Oncology (2010)

4523 Background: Outcomes of second-line targeted therapy (TT) after failure of initial anti-VEGF therapy have not been well characterized. Outcome data as well as existing prognostic criteria in this population were evaluated. Methods: Between 2005- 2009, data from patients (pts) treated with initial VEGF TT were collected from 12 cancer centers. The subset of pts who failed their first anti-VEGF therapy and then were subsequently treated with another targeted agent was analyzed for outcomes and prognostic factors. Results: From the initial cohort of 1,084 pts, 321 pts met inclusion criteria and were included in this analysis. The second-line TT was sunitinib (32%), sorafenib (45%), axitinib (3%), bevacizumab (3%), temsirolimus (11%) or everolimus (6%). From the start of the second-line targeted therapy, the median follow-up was 20.6 months (mos), the median progression-free survival was 3.7 mos, and the median overall survival (mOS) was 12.3 mos (95%CI 10-13.3 mos). Using known poor prognostic factors from the first-line setting and applying them to the second-line setting (Heng et al. JCO 2009: anemia, hypercalcemia, thrombocytosis, neutrophilia, Karnofsky performance status<80, diagnosis to treatment<1yr), pts with 0, 1-2, or 3+ risk factors were in the favorable (n=32), intermediate (n=179) and poor (n=74) prognostic groups, respectively and achieved a mOS of not reached, 13, and 5.5 mos after initiation of second-line TT (p<0.0001). The median time on first TT was 8 mos and those who were on the first-line therapy for >8 mos vs. <8 mos had a mOS of 14.3 versus 9.9 mos, respectively (p=0.006). On multivariable analysis, the duration of first-line TT continued to predict OS from initiation of second-line TT with a hazard ratio of 1.53 (95%CI 1.09-2.13). Conclusions: In pts treated with second-line TT after failure of initial anti-VEGF agents, an established prognostic model can discriminate 3 distinct risk groups. Additionally, longer time on first TT was independently associated with OS on second-line agents. No significant financial relationships to disclose.
Prevention of Meningococcal Disease
Authors: Sanford R Kimmel
Journal: New England Journal of Medicine (2007)

Invasive disease caused by Neisseria meningitidis has an average annual incidence of one case per 100,000 in the United States. The disease can be rapidly fatal or result in severe neurologic and vascular sequelae despite antibiotic therapy. Antibiotic chemoprophylaxis with rifampin, ciprofloxacin, or ceftriaxone is required for household and other close contacts. Although the majority of cases of meningococcal disease are sporadic, outbreaks can occur, and vaccination of the affected population often is necessary. Serogroup B accounts for the highest incidence of disease in young infants but is not contained in any vaccine licensed in the United States. Adolescents and young adults 15 to 24 years of age have a higher incidence of disease and a higher fatality rate than other populations. Because 70 to 80 percent of these infections in the United States are caused by meningococcal serogroups C, Y, and W-135, which are contained in the tetravalent meningococcal vaccines, they are potentially preventable. The U.S. Food and Drug Administration recently approved a meningococcal conjugate vaccine containing serogroups A, C, Y, and W-135. This T-cell-dependent vaccine induces bactericidal antibody production and promotes immunologic memory that should result in a longer duration of immunity. The Advisory Committee on Immunization Practices recommends that this vaccine be given to 11- and 12-year-old adolescents, to adolescents entering high school, and to college freshmen living in dormitories. The vaccine also may be given to persons 11 to 55 years of age who belong to certain high-risk groups.
Profile of infantile malignancies at tertiary cancer center—A study from south India
Authors: M. HS, B. Aruna Kumari, L. Appaji, S. V. Attili, D. Padma, J. Vidya
Journal: Journal of Clinical Oncology (2007)

20026 Background: Infantile malignancies are peculiar in the way they present with lot of diversity and had poor prognosis compared to other pediatric malignancies. The spectrum of malignancies had a great regional variability owing to the environmental and genetic differences (both aquired, maternal and paternal). Methods: It is a retrospective data analysis conducted at a tertiary care cancer center, Bangalore, India. The institute has an annual attendance of 16,000 new cases with reasonably good follow-up. The contribution of pediatric malignancies is 18%. The details were collected from the case records and percentages were calculated for the variables. Results: Between 2003–2006 we diagnosed 1,798 pediatric tumors. Of them 198 (11%) are infantile malignancies. The commonest diagnosis at our center is leukemia (30% of all infantile malignancies). The main types of leukemia are ALL-80%, AML-13%, and CML-7%. Other hematological malignancies are lymphomas- 2%, myelo proliferative disorders and Langerhan Cell histiocytosis-3% each. The next common diagnosis is benign neoplasms, wrongly diagnosed as malignant at the secondary referral center which contributed 16% of all cases. The reminder 46% is solid malignancies. In the decreasing frequency the incidences are Wilm’s tumor-12%, neuroblastoma-10%, germ cell tumors-8%, retinoblastoma- 6% CNS malignancies and 3% hepatoblastoma -2%. The reminders are other rare malignancies. Conclusion: The contribution of infantile malignancies at our center is relatively higher compared to the west. Similarly Relative contribution of AML to the all hematological malignancies and neurblastoma &amp; CNS tumors to solid malignancies is less compared to the existing literature. Wilm’s tumor and ALL diagnosed more frequently than expected in our population. All these findings together suggest that south Indian population had a different spectrum of infantile malignancies compared to rest of the world and their genetic and environmental risk factors need further exploration. No significant financial relationships to disclose.
Effect of epidermal growth factor receptor gene mutations on adverse events of gefitinib in patients with non-small cell lung cancer
Authors: Y. Fujiwara, K. Kiura, S. Toyooka, M. Aoe, M. Tabata, S. Hosokawa, T. Kozuki, H. Date, H. Ueoka, M. Tanimoto
Journal: Journal of Clinical Oncology (2005)

7096 Background: The objective of this study is to elucidate clinical features and adverse events of patients with or without epidermal growth factor receptor gene (EGFR) mutations during gefitinib treatment. Methods: Among 108 patients with non-small cell lung cancer who received gefitinib in our hospital between November 2000 and October 2004, EGFR mutations were searched in exons 18 to 21 by direct sequence method in 26 patients. We retrospectively reviewed the clinical records and compared EGFR mutation status with the various clinical factors and adverse events during gefitinib treatment. Results: Of all 26 patients, EGFR mutations (exon 18, 0; exon 19 in-frame deletion, 6; exon 20, 0; exon 21 L858R, 5), were detected in 11 patients and not detected in 15 patients. Patients characteristics with vs. without EGFR mutations were as follows: male/female, 36%/64% vs. 73%/27%; adenocarcinoma/others, 100%/0% vs. 73%/27%; median age, 64 (range; 40–77) vs. 68 (range; 33–77); ECOG performance status 0–1/2–4, 64%/34%, vs. 67%/33%; and smokers/never smokers, 18%/82% vs. 87%/13% (p=0.001), respectively. Response rates with and without EGFR mutations were 64% (7/11 patients) and 20% (3/15 patients), respectively. The median survival time after the initiation of gefitinib treatment was 10.8 months, with a median follow-up time of 33.4 months. Grade 3 or more toxicities by the National Cancer Institute-Common Toxicity Criteria with vs. without EGFR mutations included hepatic toxicity (0% vs. 6.7%), skin rash (18.2% vs. 0%), and diarrhea (0% vs. 0%), respectively. Pulmonary toxicity/interstitial lung disease developed in two (13.3%) patients without EGFR mutations, but did not in patients with EGFR mutations, although there was no statistical significance. Conclusions: We could not find any relationships between EGFR mutation status and adverse events during gefitinib treatment in this analysis. No significant financial relationships to disclose.
A phase I pharmacokinetic study of PR-104, a hypoxia-activated nitrogen mustard prodrug, in patients with solid tumors
Authors: M. B. Jameson, D. Rischin, M. Pegram, J. C. Gutheil, A. Patterson, W. Denny, W. Wilson
Journal: Journal of Clinical Oncology (2008)

2562 Background: This dose-escalation study defined a maximum tolerated dose (MTD) and pharmacokinetics (PK) of PR-104. In preclinical studies PR-104 is converted systemically to the corresponding alcohol PR-104A. PR-104A is reduced selectively in hypoxic cells to a DNA-crosslinking nitrogen mustard alkylating agent. Methods: Patients (pts) with advanced solid tumors refractory to standard therapy received PR-104 as a 1-hour IV infusion every 3 weeks with PK sampling on days 1–2 of cycle 1. Cohorts of >3 pts were treated starting at 135 mg/m2. With an observation of dose-limiting toxicity (DLT), cohorts were expanded to 6 pts. Results: Twenty-seven pts were treated: median age 57 years (range 30–73); 15 (56%) male. Pts had a median of 2 (range 1–5) prior regimens. Seven dose levels (135, 216, 354, 550, 770, 1,100 and 1,400 mg/m2) were evaluated. Prophylactic anti-emetics were administered starting with cohort 2. Pts received a median of 3 cycles (range 1–15). Dose levels 135 and 1,100 mg/m2 were expanded to 6 pts due to DLT of grade 3 fatigue. At 1100 mg/m2, non-DLT neutropenia resulted in cycle 2 delay in 3 of 6 pts. At 1400 mg/m2, 2 of 3 pts developed DLT (neutropenic fever and infection with normal ANC). Forty-five adverse events (AEs) were considered drug-related by the investigator. The most common AEs included fatigue (56%), nausea (41%) anemia and dysgeusia (26% each). The majority of AEs were grade 1 or 2. Five pts maintained stable disease for a median of 4.5 months (range 4–11). PR-104 PK are reported in the table below. Conclusions: The MTD and recommended dose for phase II is 1,100 mg/m2 as a 1 hour infusion every 3 weeks. The primary toxicity was dose-dependent myelosuppression, predominately neutropenia. Overall, PR-104 showed manageable toxicities. PR-104A PK appeared linear and at the MTD, exposure reached levels similar to those associated with antitumor activity in animal xenograft models. A study is underway to evaluate PR-104 in combination with prophylactic neutrophil growth factors. PR-104 Dose (mg/m2) Number of pts PR-104 Cmax (ug/mL) PR-104 AUC (ug.min/mL) PR-104A Cmax (ug/mL) PR-104A AUC (ug.min/mL) 135 6 2.1 82 1.9 118 216 3 2.8 110 3.6 209 346 3 3.4 141 3.1 226 550 3 36.4 648 14.2 876 770 3 5.7 248 8.6 514 1,100 6 18 696 15.4 1,206 1,400 3 28.5 1,116 26.4 1,818 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Proacta Therapeutics Proacta Therapeutics Proacta Therapeutics Proacta Therapeutics
Clinicopathologic evaluation of non-Hodgkin lymphoma (NHL): A single centre experience
Authors: S. Kilickap, I. Barista, E. Turkmen, O. Dizdar, S. Aksoy, A. Turker, I. Gullu, Y. Ozisik, A. Kars, G. Tekuzman
Journal: Journal of Clinical Oncology (2008)

19540 Background: We retrospectively evaluated clinicopathologic features and prognostic factors of NHL patients (pts) treated in Hacettepe University Institute of Oncology. Methods: In this retrospective study, the pts with NHL who had been diagnosed between 2000 and 2006 at our centre were evaluated. The medical records of all pts including patient characteristics, laboratory results, histopathological examinations, and imaging studies were reviewed. Survival was analyzed by the Kaplan-Meier method. Multivariate analysis of factors influencing survival was performed by using Cox proportional hazards model. Results: 358 pts (M/F: 59%/41%) were analyzed. The mean age±SD was 53.1±16.5. At the time of diagnosis, 20.1% of the pts had stage (stg) I, 28.2% had stg II, 27.4% had stg III, and 24.3% had stg IV disease. The most common histogical subtype was diffuse large-cell lymphoma (lymp) (55.3%). The rate of follicular lymp was 7%. Thirty-eight percent of the pts had B symptoms and 21% had bone marrow involvement, 17% had bulky disease. Sixteen percent of the pts had indolent lymp, 74% had agressive lymp, and 10% had highly aggressive lymp. IPI scores were for 0–1 in 37% of the pts, 2–3 in 54%, and 4–5 in 9%. During follow up, 55% of the pts relapsed. Autologous stem cell transplantation was performed in 11% of the pts. For all pts, 5-year overall survival (OS) was 52%. 5-year OS was better in pts who received CHOP-rituximab than those who received CHOP (63% vs 44%) and was better in early stages (71% for stg I vs 39% for stg IV). In univariate analysis, stage (<0.0001), performance status (ps) (<0.0001), development of relapse (<0.0001), higher LDH (p=0.0332), lower hemoglobin (=0.0023), chemotherapy (<0.0001), radiotherapy (=0.05), and grade (=0.0014) were associated with poor prognosis. In multivariate analysis, grade, development of relapse, and IPI score were independent prognostic factors for survival. Conclusions: Although the results of our study were similar to previously published studies, the frequency of follicular lymp was low compared to western societies. IPI score was the most important prognostic factor. No significant financial relationships to disclose.
Treatment of cancer of the anal canal. The Hamburg experience
Authors: V. Rudat, S. Streller, D. Rades
Journal: Journal of Clinical Oncology (2006)

14062 Background: To compare surgical and non-surgical treatment approaches for anal cancer and to identify prognostic factors. Methods: Survival data of 214 patients with cancer of the anal canal were reviewed who were referred for radiotherapy to the Department of Radiation Oncology of the University of Hamburg, Germany between 1/88 and 3/05. 75 patients received a definitive radiochemotherapy (RCT) with 5-FU and MMC according to international standards, 43 an operation followed by RCT (OP+RCT), 37 an operation followed by irradiation (OP+RT), 25 an irradiation alone (RT) and 34 an operation alone because they refused a planned adjuvant RCT or RT. The operations had been performed by different referring hospitals in and around Hamburg. Results: The median follow-up time of the living patients was 67 months (1–200 months). The 10 year overall survival rate for RCT was 0.62 (95%CI 0.46–0.77), for OP+RCT 0.65 (95%CI 0.47–0.83), for OP+RT 0.55 (95%CI 0.37–0.74), for OP alone 0.51 (95%CI 0.26–0.75) and for RT alone 0.27 (95%CI 0.05–0.48). There was no statistical difference between the overall survival of patients who received RCT, OP+RCT and OP+RT according to Kaplan Meier analysis (log rank test, p = 0.71). Cox regression analysis was used to examine the simultaneous influence of the prognostic factors T, N, age, haemoglobin concentration before radiotherapy, gender, and grading on the survival of patients who were treated with RCT. The model (p = 0.015) revealed T and N to be the only statistically significant prognostic factors. Conclusions: The different surgical and non-surgical approaches to treat cancer of the anal canal in Hamburg obviously reflect the individual preferences of the different physicians. Statistical analysis did not show a benefit of an OP added to RCT. Prognostic factors for survival after RCT were the T- and N-stage. No significant financial relationships to disclose.
Radiation and concurrent temozolomide followed by rotational multi-agent chemotherapy for glioblastoma (GBM) patients
Authors: M. L. Affronti, J. M. Day, J. E. Herndon, J. N. Rich, J. A. Quinn, D. A. Reardon, J. J. Vredenburgh, A. Desjardins, R. E. McLendon, H. S. Friedman
Journal: Journal of Clinical Oncology (2007)

2068 Background: GBM is the most lethal type of brain tumor with a 1 yr median survival. We hypothesized that GBM patients who receive adjuvant rotational multi-agent chemotherapy (temozolomide, CCNU, and CPT-11) have improved overall survival when compared to patients receiving single agent adjuvant regimens (carmustine, temozolomide). Methods: We conducted an IRB-approved retrospective data analysis of 80 primary GBM patients who received radiation therapy and concurrent temozolomide followed by 12 mos of adjuvant rotational multi-agent chemotherapy. All patients with the intent to treat were included in the analysis. The survival experience of the Duke cohort was examined within specific patient subgroups defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA). These data were compared to the recently published Stupp RPA analysis (JCO 2006) and the RTOG trial (radiation alone). Results: 73% were male. Mean age was 52 yrs (range 21–76 yrs); 39 % were &lt; 50 yrs.. 82% were white. WHO performance status was: 0, 14%; 1, 62%; 2, 20%; and 3, 4%. Overall survival was 59% (95% CI: 49%, 71%) at 1 yr and 31% (23%, 43%) at 2 yrs. Median survival was 65.1 wks (49.7, 78.9) with median follow-up of 122.1 wks.. No difference in the 2-yr overall survival rate in RPA classes III-IV was detected between the Duke and Stupp regimens (p&gt;0.4733), but 66% (33, 77) of the Duke rotational therapy GBM patients are living longer than the RTOG patients (p &gt; 0.0086). Univariate Cox Hazard ratio of 1.27 (0.522, 3.08) did not correlate MGMT status with survival (p &gt; 0.60). Conclusions: (1) Concurrent Temozolomide and radiation followed by rotational chemotherapy is an effective therapy compared to recent published gold standard adjuvant regimens. (2) Concurrent Temozolomide and radiation followed by rotational chemotherapy resulted in a statistically significant survival benefit compared to RTOG trial. (3) Lack of correlation between MGMT and overall survival suggests that agents whose damage is not repaired by MGMT may be an important therapeutic approach. (4) Future prospective randomized trials with concurrent Temozolomide and radiation must compare post radiation multi-modality regimens. No significant financial relationships to disclose.
Timely education about palliative care (PC) among pancreatic cancer patients.
Authors: Nina N. Grenon, Karen A. Sommer, Constance Barysauskas
Journal: Journal of Clinical Oncology (2014)

81 Background: A majority of cancer patients only receive PC at the end-of-life despite the physical, emotional, and existential distress throughout the continuum of the disease. The literature suggests early PC combined with standard care, improves quality of life and potentially extends survival. A four month retrospective chart review of patients diagnosed with pancreatic cancer at Dana-Farber Cancer Institute (DFCI) revealed only 19% of patients had a documented PC educational conversation within the first four weeks of care. Although early incorporation of PC education is imperative for patient quality of care it is not taking place. Methods: A quality improvement project was designed to increase the number of documented PC discussions among all new locally advanced and metastatic pancreatic cancer patients who were followed at the DFCI for the first four weeks of care. An educational brochure about PC was developed for providers and providers were educated about PC at a monthly staff meeting after completing a brief survey. Providers received an email reminder for all eligible patients and the PC brochure was attached to all patient encounter forms. Follow-up chart audits were conducted and pre and post surveys were administered to patients. Results: Providers and patients indicated no barriers to PC education. Providers indicated the onset of difficult to manage symptoms as the appropriate time to discuss PC and patients indicated first treatment or first treatment failure as the appropriate time to discuss PC. Chart audits revealed all eligible patients were educated about PC between April 14 and May 9, 2014 (n=13). Conclusions: Following implementation of this successful initiative, all eligible patients were educated about PC, conversations were documented and providers identified no barriers in the process. Due to the small scope of this project, further work is needed to improve sustainability, including ongoing identification of the number of patients who enroll in PC services concurrently with standard care, measure patient satisfaction, and implement our initiative in additional disease centers. In the future, infusion nurses, practice nurses, and social workers will participate in PC education training.
Comparing radioguided occult lesion localization (ROLL) vs wire guide (WGL) for impalpable breast cancers
Authors: H. S. J. Ramesh, R. A. Audisio, R. Nadeem, L. S. Chagla, R. Thind, O. Harris, S. Desmond, C. Titterrell
Journal: Journal of Clinical Oncology (2005)

765 Background: Over 30% breast lesions removed are occult due to increased screening mammography. Optimum excision & maintaining aesthetic outcomes is a surgical challenge. There is demand for an ideal localization technique, despite availability of several techniques. Current standard in UK is WGL. Since 2002 modified ROLL technique is used at our Breast Unit. We compare our consecutive ROLL & WGL series Materials & Methods: 80 occult breast cancers, prospectively localized and treated with ROLL (12/02–09/04) have been compared with a consecutive series of 80 localized with WGL (04/98–11/02). Intra-lesion injection of 99Tc-labelled nanocolloid under ultrasonography/stereotaxis occurred 2hrs before surgery. Per-operative localization is performed under γ-probe guide. Among variables analyzed, focus is drawn to localization/excision time, hospital stay, cancer size, weight/volume of the excised specimen and clearance margins. Tumor volume and volume of excised specimen are derived from pathology reports. Computation techniques used to calculate theoretical volume of ideal specimen with 1cm safe margin. Concentricity of the lesion is calculated by ratio of the excised specimen’s volume to the volume of the ideal excised specimen and ratio of the excised specimen’s volume to the tumor volume Results: The two groups were comparable for median age, x-ray abnormalities, type of surgery & final histology. Median hospital stay (p=0.607) & operative time (P=0.118) failed to achieve statistical significance. Median pathological tumor size was larger in the ROLL group (18 mm) than WGL (15mm) (P=0.770).No major complication/technical fault was recorded. Cost of 99mTc is £28/patient, compared to £35/patient for wire Conclusions: ROLL is a reliable localization technique for occult breast cancers. Added benefits are quicker localization, cost effectiveness, & increased rates of clear margin while maintaining superior cosmetic results No significant financial relationships to disclose.