tbuckley/cabot-search huggingface dataset:
Factors influencing late rectal toxicity after radiotherapy of localized prostate cancer
Authors: G. Lim, H. Lau, S. Brar, S. Angyalfi, A. Balogh
Journal: Journal of Clinical Oncology (2005)

4730 Background: Radiation injury to the rectum is a common sequelae of radiotherapy to the prostate because of the proximity of the rectal wall to the prostate. The objective of this article will be to review the experience at this institution and identify factors influencing late rectal toxicity after radiotherapy for localized prostate cancer. Methods: The cohort consists of 426 patients with localized prostate cancer treated with conformal radiotherapy from September 2000 to March 2003. RTOG scales were used to evaluate late rectal morbidity and a modified CTC/RTOG scale was used to grade late rectal bleeding at each follow up visit. Patients were assessed 6 - 8 weeks after radiation, and then every 6 months. The endpoints of interest included: rectal toxicity grades 2–4, any late rectal bleeding, and late rectal bleeding grades 2–4. Patient and treatment factors were analyzed. Results: The median ICRU prostate dose was 73.7 Gy (range 50–82 Gy). Pelvic lymph node irradiation was given in 15% of patients. Neoadjuvant hormones were given in 80% of patients. Median follow-up of the patients was 17.5 months. No patient developed grade 4 toxicity. The 18 month Kaplan-Meier rates of late rectal bleeding grade 2–3, any rectal bleeding, and ano-rectal toxicity grade 2–3 was 8.5%, 24.9%, and 17.1%. Univariate analysis of patient factors including age, cardiovascular disease, diabetes, hypertension, and weight did not show any influence on rates of late rectal bleeding. However, treatment factors including the percent rectum receiving greater than 60Gy and 70Gy and the total prostate dose were significant in increasing grade 2–3 ano-rectal toxicity. The percent rectum receiving greater than 70Gy and total prostate dose were significant in increasing grades 1–3 rectal bleeds. Conclusions: The volume of rectum receiving greater than 60Gy and 70Gy is significant in influencing rates of late rectal toxicity and should be minimized. Rectal bleeds and ano-rectal toxicity are also affected by the total prostate dose and should be monitored carefully in dose escalation trials. No significant financial relationships to disclose.
The effect of hypertensive blood pressure response during stress echocardiography on the predictive value of decreased stress ejection fraction for severe CAD
Authors: S. Solis, A.F. Osman, L. Orejarena, C.J. Lavie, A. Grant, Y.E. Gilliland, M.M. Cassidy, J.A. Bernal, R.V. Milani
Journal: Journal of the American College of Cardiology (2000)
Emergence of Ymdd Lamivudine Resistance After Transplantation of Anti-Hbc Positive Donor Livers Into Anti-Hbc Negative Recipients Using Lamivudine Monotherapy Prophylaxis
Authors: Humberto E. Bohorquez, Ari J. Cohen, Ian C. Carmody, David S. Bruce, Shobha Joshi, Brian B. Borg, Nigel Girgrah, George E. Loss
Journal: Hepatology (2011)
The relationship between the shuttle walk test, lung function and BMI in patients with sarcoidosis
Authors: Rebecca Frank, Colm Leonard, Jayne Holme, Annette Duck
Journal: European Respiratory Journal (2012)

Introduction

Monitoring patients with sarcoidosis is important and challenging. The incremental shuttle walk test is used in outpatient settings and we assessed its correlation with lung function, BMI and age.

Method

A retrospective study of data from 63 patients with sarcoidosis who had had a shuttle walk with their lung function tests. Spearman's correlation coefficient rs was used to assess the relationship between the shuttle walk (distance walked, oxygen saturations) and Borg score (before and after exercise), with lung function (FEV1, FVC and DLCO[% predicted]), age and BMI. A stepwise multiple linear regression model of distance walked was developed.

Results

Correlation is seen between the shuttle walk and lung function.(table1)The distance walked also correlated with age (rs=-.372, p=.003) and BMI (rs=-.303, p=.016). There was correlation between the Borg score post exercise and the BMI (rs=.253, p=.046). The multiple regression model of distance walked identified BMI (t=-3.195, p=.002), age (t=-2.963, p=.002) and FEV1 (t=3.061, p=.003) as significant independent variables.

View this table:

Correlation between shuttle walk test and lung function





Conclusion

The shuttle walk test may be useful in monitoring patients with sarcoidosis as it correlates with lung function. The influence of BMI on distance walked cannot be underestimated.
Sunitinib in patients with or without prior nephrectomy (Nx) in an expanded access trial of metastatic renal cell carcinoma (mRCC)
Authors: C. Szczylik, C. Porta, S. Bracarda, R. Hawkins, G. A. Bjarnason, S. Oudard, S. Lee, G. Carteni, S. Hariharan, M. E. Gore
Journal: Journal of Clinical Oncology (2008)

5124 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs that has demonstrated substantial antitumor activity in the first- and second-line mRCC settings (JAMA 2006;295:2516; NEJM 2007;356:115). Here, we present an analysis of outcome for patients (pts) with or without prior Nx (including partial resection) receiving sunitinib in an ongoing, international, open-label expanded access trial. Methods: The purpose of this trial was to provide sunitinib prior to regulatory approval to mRCC pts without access to study drug due to trial ineligibility or other reasons; thus, eligibility criteria were minimized to broaden enrollment. Pts ≥18 yrs with histologically-confirmed mRCC received sunitinib 50 mg orally, once-daily in 6-wk cycles (4 wks on treatment [Tx], 2 wks off). Results: As of December 2007, 4,616 pts had been enrolled. At the time of analysis, data were available for 3,997 pts of whom 3,507 pts (88%) had prior Nx compared with 490 pts (12%) who had not. Within these subgroups, the sites of metastatic disease at baseline were similar (brain: 8% and 7% of pts, respectively; lung: 78% and 71%; bone: 34% and 40%; liver: 27% and 30%; lymph nodes: 51% and 55%; and other: 28% and 25%); the proportions of pts with ECOG PS ≥2, non-clear cell RCC, and who were ≥65 yrs of age were 12% and 22%, 13% and 19%, and 32% and 37%, respectively; 2,595 pts (74%) and 259 pts (53%), respectively, had prior cytokine Tx before sunitinib. Of pts with (n=2,733) and without (n=331) prior Nx (and for whom data were available), the objective response rates were 16% and 9%, respectively (19 pts [<1%] and 0 pts with a complete response, respectively, and 405 pts [15%] and 30 pts [9%] with a partial response); 59% and 55% of pts, respectively, had stable disease ≥3 mo. For pts with prior cytokine Tx, median progression-free survival (PFS) was 9.8 months and 8.0 months for pts with and without prior Nx, respectively; for pts without prior cytokine Tx, median PFS was 9.4 months and 6.0 months for pts with and without prior Nx. Conclusions: Sunitinib demonstrated antitumor activity in mRCC pts with or without prior Nx for whom baseline metastatic disease burden was similar in both groups. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Bayer, Glaxo, Pfizer, Roche, Schering-Plough, Wyeth Pfizer Pfizer Bayer, Pfizer Pfizer
Hypertensison is a significant adverse effect of bevacizumab treatment
Authors: M. A. Lowery, D. G. Power, A. T. Behbehani, D. N. Carney, J. A. McCaffrey
Journal: Journal of Clinical Oncology (2007)

14134 Introduction: Vascular endothelial growth factor (VEGF) is upregulated in many tumours. Bevacizumab (BV) is a recombinant, humanised monoclonal antibody against the VEGF receptor and has shown promising results in phase II / III trials in colorectal cancer, non-small cell lung cancer, renal cell carcinoma, and breast cancer. Hypertension (HT) has been reported in all studies involving BV and management of this is not well established. Methods: The records of patients treated with BV in our institution were analyzed from January to August 2006. Indications for BV therapy, incidence and management of HT, and resulting outcomes were assessed. Results: 71 patients (45 male, 28–84 years) were treated with BV, at a dose of 5mg/kg every two weeks. 87% (n=60) had colon cancer. Lung cancer, renal cell carcinoma, melanoma, and pancreatic cancer accounted for the rest. 20% (n=14) had pre-existing HT. In all of these cases HT was well controlled with medication. 10 patients developed new-onset HT, and 7 patients experienced exacerbation of existing HT. Using the CTCAE(v3.0) guidelines for grading of HT, 5 had grade II and 10 had grade III. HT developed after a median of 15 weeks of BV (range 6–36 weeks), and a median cumulative BV dose of 20mg/kg (range 10 - 85 mg/kg). In the new onset HT cases 8 patients were controlled (BP= 140/90) with a single anti-HT, and one patient needed two or more agents (BP&lt;160/100). In the pre-existing HT cases who needed an adjustment of anti-hypertensives, 3 were controlled (BP=160/100) with two or more agents and 4 patients required dose escalation of a single agent. In 2 patients BV was permanently discontinued. Anti-HT agents used included beta-blockers, ACE-inhibitors and Ca ++ - channel blockers. Conclusions: HT may develop at any point during treatment with BV. BP should be measured regularly. In this study 14% of patients developed HT de novo, and 50% experienced exacerbation of pre-existing HT. Median time to BV-induced HT was 15 weeks. There is currently no data to define which anti-HT is the best to use. BV is now becoming widely used, and as with all new targeted therapies, it is important that oncologists recognise relatively unusual side effects, and develop appropriate practice guidelines. No significant financial relationships to disclose.
Reflex testing of lung adenocarcinomas for <i>EGFR </i>and <i>KRAS</i> mutations: The Memorial Sloan-Kettering experience
Authors: M. F. Zakowski, M. Ladanyi, N. Rekhtman, B. J. Park, D. Finley, C. G. Azzoli, G. J. Riely, V. W. Rusch, M. G. Kris
Journal: Journal of Clinical Oncology (2008)

22031 Background: Primary lung adenocarcinoma is preferentially susceptible to tyrosine kinase inhibitors (TKI). Identification of activating mutations in EGFR TK domain is thr best predictor for sensitivity/response to EGFR TKIs. These mutations are not found in association with KRAS mutations. The presence of a KRAS mutation contraindicates EGFR TKI therapy indicating other agents, or investigational therapies. Given the high rate of recurrence of adenocarcinoma, and frequent difficulties/delays in obtaining archival material for molecular testing at recurrence (necessitating in some patients a second procedure), we instituted routine reflex testing for EGFR and KRAS mutations of all resected lung adenocarcinomas. Methods: At the time of gross prosection, a slice of tumor is frozen and retained along with a corresponding section for paraffin embedding and H&E staining. When histology shows adenocarcinoma, frozen tissue and corresponding H&E slide are sent to the molecular diagnostic laboratory for extraction of DNA and identification of EGFR exon 19 deletions and exon 21 L858R mutations by PCR assays. In samples lacking EGFR mutations, KRAS analysis is done by direct sequencing of PCR products. If frozen tissue is unavailable, the paraffin block serves as an alternate source of DNA. A molecular diagnostic report is issued to the clinician before the patient's post-op or oncology visit, and becomes part of the medical record. Results: Reflex testing started in 2006. In a one year period, over 500 lung resections were performed. 297 adenocarcinomas, including wedge resection, segmentectomy, lobectomy, bilobectomy, and pneumonectomy were successfully studied. 294 (98%) of cases were studied for both EGFR and KRAS. There were 58 (20%) EGFR mutant cases and 85 (28%) KRAS mutant cases. Interestingly, there were 13 Asian patients with an EGFR mutation rate of 53% and no KRAS mutations; 11 black patients had a 9% EGFR mutation rate and 45% KRAS mutation rate. Conclusions: Mutations in exons 19 and 21 of EGFR and exon 2 of KRAS are common in resected specimens from patients with lung adenocarcinoma. Reflex testing for EGFR and KRAS mutations is easily implemented and ensures that key molecular data are available to inform and expedite subsequent treatment decisions. No significant financial relationships to disclose.
Human Breast Tumor Cell Lines: Identity Evaluation by Ultrastructure 2
Authors: A Gertrude C. Buehring, Adeline J. Hackett
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Human Breast Tumor Cell Lines: Identity Evaluation by Ultrastructure Get access A Gertrude C. Buehring, A Gertrude C. Buehring Search for other works by this author on: Oxford Academic PubMed Google Scholar Adeline J. Hackett Adeline J. Hackett 3School of Public Health and its Cell Culture Laboratory, University of California, Berkeley, Calif. 94720. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 3, September 1974, Pages 621–629, https://doi.org/10.1093/jnci/53.3.621 Published: 01 September 1974 Article history Received: 12 February 1974 Accepted: 30 May 1974 Published: 01 September 1974
Independent radiologic review of GOG218, a phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian (EOC), primary peritoneal (PPC) or Fallopian tube cancer (FTC).
Authors: R. A. Burger, M. F. Brady, J. Rhee, M. A. Sovak, H. Nguyen, M. A. Bookman
Journal: Journal of Clinical Oncology (2011)

5023 Background: GOG218 is a phase III randomized, double-blind, placebo-controlled trial with three arms comparing both carboplatin and paclitaxel (CP) plus concurrent, or concurrent plus continued BEV (CP+B-->B) in stage III (with macroscopic residual disease) and stage IV EOC, PPC or FTC. Investigator assessment showed a clinically meaningful and statistically significant improvement in progression-free survival (PFS) for CP+B-->B when compared with CP therapy alone (R.A. Burger, ASCO 2010 LBA1). The PFS hazard ratios (HR) from the uncensored and censored (censored for CA-125 and non-protocol therapy, INVc) analyses were 0.72 (p< 0.0001) and 0.644 (p< 0.0001), respectively. To determine the reliability of RECIST in assessing progression in ovarian cancer, an independent review of blinded radiologic and clinical data was conducted to confirm these results. Methods: Radiographic images and clinical data were provided to the independent review committee (IRC). Data were reviewed in a blinded fashion, in accordance with a pre-specified charter following RECIST criteria. PFS was analyzed as an intent-to-treat analysis of all randomized subjects. Results: Images were submitted for over 97% of patients. High concordance between IRC and INVc was observed for progressive disease (PD) status (77%) and PD date (73%). Further analysis of concordance and validation of other study endpoints is ongoing. Conclusions: This is the largest IRC analysis ever conducted in patients with ovarian cancer, to our knowledge. The IRC and INVc PFS analyses were highly consistent, both confirming a significant increase in PFS for subjects treated with CP+B-->B versus CP alone. The size of the IRC, high participation rate, and strong concordance observed between IRC and INVc suggest that RECIST criteria can be applied objectively in primary ovarian cancers. IRC INVc CP N=625 CP+B-->B N=623* CP N=625 CP+B-->B N=623* PFS (HR) 0.630 0.644 P value (log rank) <0.0001 <0.0001 Median (months) 13.1 19.1 12.0 18.2 * Events prior to cycle 7 from the concurrent and CP + B-->B arms were pooled for analysis.
ECOG 2204: An intergroup randomized phase II study of cetuximab (Ce) or bevacizumab (B) in combination with gemcitabine (G) and in combination with capecitabine (Ca) and radiation (XRT) as adjuvant therapy (Adj Tx) for patients (pts) with completely resected pancreatic adenocarcinoma (PC).
Authors: J. Berlin, P. J. Catalano, Y. Feng, A. M. Lowy, A. W. Blackstock, P. A. Philip, R. R. McWilliams, J. L. Abbruzzese, A. B. Benson
Journal: Journal of Clinical Oncology (2010)

4034 Background: At the time this study was developed, Ce and B were being investigated as part of tx for advanced PC. Concern existed over safety of adding Ce or B to standard adj tx if either drug proved to be active in advanced PC. Methods: Pts with resected PC, ECOG PS 0-1 and adequate bone marrow and liver function were eligible to be randomized to either Ce (arm 1) or B (arm 2) in combination with a standard regimen of G given before and after capecitabine (625 mg/m2 bid on days of XRT only) + XRT (50.4 Gy). CE (400 mg/m2 day 1, then 250 mg/m2 weekly), or B (5 mg/kg q 2 weeks until end of XRT, then 10 mg/kg q 2 weeks), was given throughout therapy. Primary endpoint was rate of pre-specified toxicities (tox) of concern assessed prior to start of XRT and at end of all therapy. This study had a 2-stage design with interim analysis at 25 pts per arm. A total of 126 pts were required assuming a 5% ineligibility and 85% power to detect a 35% rate of specific toxicites. Disease-free (DFS) and overall survival (OS) were secondary endpoints. Results: 137 pts were enrolled, 129 eligible for analysis, 67 on arm 1 and 62 on arm 2. Median age was 60 and 81% had pancreas head primary on both arms. PS (0/1/2) was 40/60/0% in arm 1 and 48/48/3% for arm 2. 65.7% of pts on arm 1 and 54.8% on arm 2 completed adj tx per protocol. 9% on arm 1 and 12.9% on arm 2 recurred while on therapy and 14.9% on arm 1 and 22.6% on arm 2 stopped treatment due to tox/complications. 1 treatment-related death on arm 2 was due to colon perforation. DFS at 2 years was 16% on arm 1 and 22% on arm 2. OS at two years was 35% on arm 1 and 37% on arm 2. Prior to start of XRT, 9% in arm 1 and 2% in arm 2 experienced prespeciified grade 3/4 tox of concern. At end of all therapy 27% on arm 1 and 23% on arm 2 had pre-specified gr 3/4 tox of concern, mostly hematologic. Conclusions: Both arms were safe and fairly well tolerated. Over 10% of pts recurred during adj tx even without planned disease assessments. There is no evidence to develop either arm further in adj tx of PC. Efforts should focus on developing new agents and defining whether or not XRT has a role in adj tx of PC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech/Roche, ImClone/Lilly Genentech/Roche, ImClone/Lilly
Phase I and Pharmacokinetic Study of Combination Chemotherapy Using Irinotecan and Paclitaxel in Patients with Lung Cancer
Authors: Gyo Asai, Nobuyuki Yamamoto, Takayasu Kurata, Kenji Tamura, Hisao Uejima, Kazuhiko Nakagawa, Masahiro Fukuoka
Journal: Journal of Thoracic Oncology (2006)
Preliminary safety and efficacy data of a phase II trial of vinflunine and cetuximab in the second-line treatment of patients with advanced non-small cell lung cancer
Authors: T. E. Stinchcombe, C. B. Lee, D. N. Hayes, J. K. Choksi, T. Allred, S. Gulino, B. F. Qaqish, M. A. Socinski
Journal: Journal of Clinical Oncology (2008)

19100 Background: Vinflunine, a novel vinca-alkaloid, and cetuximab, a monoclonal antibody against the epidermal growth factor receptor (EGFR), have both demonstrated single agent activity in patients (pts) with advanced non-small cell lung (NSCLC) who have progressed after platinum-based therapy. Vinflunine and cetuximab may have significant activity therefore we performed a phase II trial to investigate the activity and toxicity of this combination. Methods: Pts with stage IIIB/IV NSCLC who had progressed after first-line therapy, a performance status (ECOG PS 0–2), and adequate bone marrow, renal and hepatic function were eligible. Pts with grade ≥ 2 sensory neuropathy were excluded. Pts received vinflunine 320 mg/m2 every 21 days, and cetuximab 400 mg/m2 on day 1 cycle 1, followed by cetuximab 250 mg/m2 weekly. One cycle consisted of three weekly cetuximab infusions and one vinflunine administration (1 cycle=21 days). The primary endpoint was overall response, and the trial employed a min-max two-stage design and the treatment would be declared ineffective if < 2 responses were observed in the first 27 pts. Results: 18 pts were enrolled, 2 pts were consented and not treated, and 16 pts received treatment. The patient demographics are: median age = 60.5 years (range 50–72), the majority of pts were white (n=16), were male (n=9), and had a performance status of 0–1 (n=16). Pts received 38 cycles of therapy on trial. Grade 3 or 4 toxicities observed include: neutropenia (n=10), cetuximab hypersensitivity reaction (HSR) (n=3), constipation (n=3), abdominal pain (n=2), nausea (n=1), and vomiting (n=1). Three pts were non-evaluable related to cetuximab related HSR on the first cycle, 13 pts were evaluable for response. Responses observed were: partial response (n=3), stable disease (n=5), progressive disease (n=4), and non-evaluable (n=1). Conclusion: On preliminary review, vinflunine and cetuximab has demonstrated activity. The most frequent toxicities appear to be neutropenia, cetuximab HSR, abdominal pain, and constipation. Consistent with previous reports, we continue to observe a higher than expected rate of cetuximab-HSR. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb
Do racial differences predict survival amongst VA patients with colon cancer?
Authors: M. Safa, M. Atiq, R. Komrokji, Z. Nahleh, J. Pancoast, A. Muhleman, A. R. Jazieh
Journal: Journal of Clinical Oncology (2006)

3628 Background: Several reports suggested that African-American patients with colon cancer have poor survival. The outcome of colon cancer in patients treated within the VA system is not well studied. Patients treated in the VA usually share common features and socioeconomic class that will allow studying any potential effect of racial difference on outcome. Methods: We used the VA Central Cancer Registry (VACCR) to analyze VA patients with colon cancer diagnosed between 1995–2005. The reference date for data collection and reporting is January 1, 1995. Data are entered by tumor registrars at the VA medical centers. This site aggregates the data collected by the medical centers’ cancer registries. Data was analyzed using bio-statistical software SPSS. Results: There were a total of 14,816 cases with invasive adenocarcinoma.Majority of patients (98%) were males. Median age was 69 years among caucasian patients as compared to 67 years among African- American (p-value &lt;0.005). There was no difference between the two groups with regards to sex, histological grade, histological subtype, use of chemotherapy or radiation therapy. However, African-Americans had less definitive surgery (84% vs. 86%) (p-value 0.003).The staging information was missing or unknown in 59% of the patients. In patients with known stage, no difference was observed.Median survival for caucasians was greater than African-Ameircans (42 months vs. 39 months)(p-value 0.009). Median survival for stage IV patients was not statistically significant between the two groups (8.8 months vs. 8.6 months);(p-value 0.53). Race was not statistically significant independent variable in Cox multiple regression analysis. Conclusions: In the VA system, African-American patients with colon cancer seem to have a trend towards inferior survival. However, race was not an independent prognostic variable. This slight difference could be due to other variables like definitive surgery. No significant financial relationships to disclose.