tbuckley/cabot-search huggingface dataset:
Real-world impact of availability of adjuvant therapy (AT) on outcomes in patients (pts) with resected pancreatic adenocarcinoma (PC): A Canadian cancer agency experience.
Authors: C. Kim, S. Gill, D. Owen
Journal: Journal of Clinical Oncology (2010)

e14582 Background: Pts with resected PC have a poor prognosis, with a 5-year overall survival (OS) of 10%-25%. In 2004, ESPAC1 showed that the use of AT with 5-FU improves OS. Subsequently, the British Columbia Cancer Agency (BCCA) introduced guidelines to offer AT as the standard of care for pts with resected PC. This study reviews the OS and disease free survival (DFS) in a pre-AT era (2000 to 2004) to the AT era (2005 to 2008) at the BCCA. Methods: The majority of pancreatic resections in the province of British Columbia take place at the Vancouver General Hospital (VGH). Using pathology records, all PC resections at VGH from 2000 to 2008 were identified. All pts referred to the BCCA were captured by the Cancer Agency Information System. Treatment records were obtained from the BCCA pharmacy database. Charts were reviewed to abstract demographics, pathologic stage, grade, margin status, performance status (PS) at referral, DFS and OS. Outcomes were compared by log-rank comparison. Results: In the pre-AT era, 53 resections were recorded, with 64% referred to the BCCA. Pt characteristics: median age 65y (range 45-83); female 50%, node positive 82%, poorly differentiated 59%, margin-positive 38%, PS 0-2 59%. 24% of pts received AT: all 5FU. AT completion rate 75%. In the AT era, 74 resections were recorded, with 88% referred. Median age 65y (range 38-82), female 58%, node positive 70%, poorly differentiated 34%, margin-positive 34%, PS 0-2 83%. 69% of pts received AT: 61% 5FU, 39% gemcitabine. AT completion rate 61%. Major reasons for no AT: delayed referral or metastases at time of referral 45%, poor PS 35%. Pre-AT DFS 13 mos vs. 15 mos AT era, p = 0.55. Pre-AT OS 19 mos vs. 18 mos AT era, p = 0.59. Conclusions: Since the guideline for AT, there was an increase in the proportion of patients referred, however, over 30% still do not receive or complete AT. In the AT era, pts received 5FU or gemcitabine, both equivalent options based on ESPAC3 (ASCO2009). There was no difference in survival outcomes between the pre-AT and AT eras. Our observed median survival of 18 mos is inferior to the 23 mos reported in ESPAC3. Strategies to improve rate and timeliness of referral should be explored. No significant financial relationships to disclose.
Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of ORAL LBH589B: A novel histone deacetylase (HDAC) inhibitor
Authors: J. Beck, T. Fischer, D. George, C. Huber, E. Calvo, P. Atadja, B. Peng, C. Kwong, S. Sharma, A. Patnaik
Journal: Journal of Clinical Oncology (2005)

3148 Background: ORAL LBH589B is a novel, orally administered histone deacetylase inhibitor which inhibits HDAC enzyme activity, activates p21, and inhibits proliferation of tumor cell lines at nanomolar concentrations. This phase I study tested the safety and tolerability of oral LBH589B in patients with advanced solid tumors or lymphoma. Methods: In this phase I trial, LBH589B is administered PO on 2 dosing schedules, MWF of a 28-day cycle (arm 1) or continuous daily dosing (arm 2, not yet open). Results: Nine pts (median age: 64 years; 8M, 1F) have been treated in arm 1 at 2 dose levels (mg/day): 15 (3 pts) and 30 (6 pts). Tumor types: renal (3 pts), prostate (2 pts), renal/pelvis (1 pt), colon (1 pt), other (2 pts). No DLTs have been observed to date. Other toxicities seen (all cycles): diarrhea (G3 - 1 pt, G2 - 4 pts), thrombocytopenia (G3 - 1 pt, G2 - 1 pt), G2 fatigue (4 pts), G2 weakness (1 pt), G2 anorexia (2 pts), G2 nausea (3 pts), G2 vomiting (1 pt). Out of 250 ECGs analyzed, 2 patients, dosed at 30 mg, had an increase in QTcF from baseline of 50–60 msec (none with QTcF >500 msec). Western blots were performed on total cell lysates from peripheral blood lymphocytes (PBLs) to study histone acetylation (HA). Five of 6 patients in the 30mg dose cohort showed increased and sustained HA in PBLs for at least 24 h after dosing. Plasma PK profiles were analyzed on Days 1, and 8 or 15. PK parameters derived from plasma concentration time curves were determined by non-compartmental analysis. LBH was rapidly absorbed after oral administration with a mean Tmax of approximately 2 hr. Cmax ranged from 6.6 ± 3.8 (15 mg) to 9.4±5.8 (30 mg) ng/mL at steady state. The AUC0–24 of LBH589 increased proportionally from 90.2±46.9 hr.ng/mL (15 mg) to 153.1±35.8 hr.ng/mL (30 mg). There was a 1.5 fold drug accumulation at steady state. The terminal half-life averaged 16.5 hrs. Comparison of AUC with iv administration indicated a 17% of absolute bioavailability. Conclusions: In this phase I study, LBH589B given orally appears to be well tolerated with consistent PD effects and PK. Additional evaluation is continuing at 30 mg/day and further dose escalations are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Germany, Novartis Novartis Novartis Germany Novartis Germany
Outcomes of adjuvant chemotherapy (AC) in young (YP) and elderly patients (EP) with high-risk stage II colon cancer (CC).
Authors: Aalok Kumar, Hagen F. Kennecke, Howard John Lim, Daniel John Renouf, Sharlene Gill, Ryan Woods, Caroline Speers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2014)

398 Background: High-risk stage II CC is defined as those presenting with T4 stage, obstruction or perforation, &lt;12 lymph nodes retrieved, positive resection margins, and lymphovascular or perineural invasion. Our prior findings suggest that improved outcomes from AC are limited to specific high-risk features, such as T4 disease (Kumar et al, ASCO 2012). It is unclear if this benefit is seen across all ages. Our aim was to compare patterns of AC use and outcomes in YP and EP with high-risk stage II CC. Methods: All patients diagnosed with high-risk stage II CC from 1999 to 2008 and evaluated at any 1 of 5 regional cancer centers in British Columbia were categorized into YP (age &lt;70 years) or EP (age &gt;/=70 years). Kaplan-Meier methods and Cox regression were used to correlate receipt of AC with overall survival (OS), disease specific (DSS), and relapse-free survival (RFS), stratified by age group. Results: A total of 1,236 patients were identified: 636 (51%) YP and 600 (49%) EP among whom 363 (57%) and 85 (14%) received AC, respectively. Individuals who received AC in either age group had better performance status than those who did not (ECOG 0/1 47% vs. 34%, p=0.02). After adjusting for known prognostic factors, a significant advantage in OS, but not DSS or RFS, from AC was observed for both YP and EP (Table). The impact of AC on these outcomes was similar across age groups (p interaction of age and treatment = 0.46, 0.64, and 0.69 for OS, DSS, and RFS, respectively). In the entire cohort, individuals with T4 lesions had significantly improved OS (HR 0.50, 95%CI 0.33-0.77, p=0.002), DSS (HR 0.59, 95%CI 0.37-0.93, p=0.03), and RFS (HR 0.63, 95%CI 0.42-0.95, p=0.03). The effect of AC in the T4 subgroup was also similar for both YP and EP in terms of OS, DSS and RFS (p interaction of age and treatment = 0.41, 0.71, and 0.77, respectively). Conclusions: In this population-based cohort of high-risk stage II CC, improvements in outcomes from AC were seen mainly in those with T4 disease, regardless of age. [Table: see text]
Multidisciplinary approach for cT1bN0 esophageal cancer.
Authors: Toshiro Iizuka, Daisuke Kikuchi, Shu Hoteya, Mitsuru Kaise, Harushi Udagawa
Journal: Journal of Clinical Oncology (2016)

133 Background: The standard treatment for cT1bN0 esophageal squamous cell carcinoma (ESCC) was once surgery, but endoscopic submucosal dissection (ESD) following by additional treatment (ESD+α) are now being applied. Accordingly, we examined treatment outcomes for cT1bN0 ESCC to assess the validity of these treatments in terms of diagnostic accuracy and post-treatment prognosis. Methods: A total of 174 patients with ESCC were diagnosed as cT1b by endoscopic ultrasound (EUS) and white-light imaging between January 2008 and December 2014. Twenty-six patients diagnosed as cN+ by EUS or CT/PET were excluded. The diagnostic accuracy of invasion depth and lymph node metastasis was analyzed along with the post-treatment prognosis. Results: Initial treatment was ESD for 102 patients (ESD group) and surgery for 46 patients (surgery group). The histological diagnosis was T1a in 63 patients and T1b in 85 patients, meaning that 57.4% of the patients were accurately diagnosed. In the surgery group, 30 patients (65.2%) were accurately diagnosed as cN0. In the ESD group, 80 patients had an invasion depth of T1a-MM or deeper, which has a potential risk of metastasis. Additional surgery was performed for 15 patients, additional chemotherapy or chemoradiotherapy was performed for 43 patients, and follow-up without additional treatment was for 22 patients. Recurrence during follow-up was observed in 8 patients (lymph nodes in5 patients; other organs in 3 patients). Of the 16 patients with histological lymph node metastasis in the surgery group, 10 underwent adjuvant chemotherapy. Recurrence was noted in 3 patients (lymph nodes in 1 patient; other organs in2 patients). The mean follow-up period was 39 months for the ESD group and 45.8 months for the surgery group. Three- and five-year survival rates were respectively 93.1% and 79.3% in the ESD group and 89.8% and 85.1% in the surgery group, with no significant differences between the groups. Conclusions: Accuracy of preoperative diagnosis of invasion depth is still not high, which makes the ESD+α strategy an acceptable. As mid- to long-term outcomes were favorable in both groups, it appears that favorable outcomes can be obtained by performing multidisciplinary therapy based on the histological diagnosis.
Lung cancer histology in a Brazil: A retrospective study of 1,887 patients.
Authors: G. Ismael, A. L. Coradazzi, A. V. Cantarelli, K. C. Abdalla, E. R. Mattos, J. d. S. Oliveira, C. Manzoni, C. A. d. M. Beato, J. G. M. Segalla
Journal: Journal of Clinical Oncology (2011)

e18039 Background: Lung cancer remains as the leading cause of cancer deaths. During the last decades, it was observed a decline in the prevalence of small cell lung cancer (SCLC), while adenocarcinoma has been reported as the most common histological subtype in patients with non-small cell lung cancer (NSCLC). There are few studies analyzing lung cancer histology in Latin America. Methods: The present study aims to evaluate the clinical and histopathological data related to patients with lung cancer at the Hospital Amaral Carvalho, Jau (SP), in Brazil, between 1997 and 2008. Data of 1,887 patients were retrospectively evaluated, considering clinical and histopathological data. Results: From this population, 182 patients (9.6%) were diagnosed as Stage I, 122 (6.6%) with stage II, 632 patients (33.7%) as stage III and 695 patients (36.9%) as stage IV. A total of 256 patients (13.2%) didn’t present enough data to determine correct clinical stage. These data indicate a high incidence of patients diagnosed with advanced and incurable disease. We found 199 patients with SCLC (10.5%) and 1,688 patients with NSCLC (89.5%). From patients with NSCLC, they were divided into five subgroups: 516 patients with adenocarcinoma (27.4%), 482 patients with squamous cell carcinoma (25.5%), undifferentiated carcinoma was diagnosed in 245 patients (13%), large cell carcinoma in 122 patients (6.5%) and 323 patients (17.1%) were founde with other histological subtypes. We compare different periods (1997 to 2002 and from 2003 to 2008) as an attempt to evaluate differences between the proportions of SCLC and NSCLC and among histological subgroups within the population with NSCLC, which could suggest a change in the presentation of lung cancer in this population. A reduction in the proportion of SCLC was founded, but no significant changes between the histological subgroups among patients with NSCLC were reported, with adenocarcinoma being the most frequent histological subtype in both periods. Conclusions: These data suggest that our lung cancer patients presented a declining incidence of SCLC and adenocarcinoma has been the most frequent histological subtype among NSCLC patients.
Utility of PET/CT as initial staging work up for early pancreatic cancer.
Authors: Gopi Kesaria Prithviraj, Nishi Kothari, Binglin Yue, Jongphil Kim, Gregory M. Springett, Mokenge Peter Malafa, Pamela Joy Hodul, Richard D. Kim
Journal: Journal of Clinical Oncology (2014)

183 Background: In pancreatic cancer, early detection and complete surgical resection with negative margins offers the only cure for the disease. Work up to evaluate resectability includes triple phase helical scan CT of the pancreas and endoscopic ultrasound (EUS). A paucity of data exists in using PET/CT scan as staging work up in early resectable pancreatic cancer. The objective of our study was to determine if PET/CT prevents futile laparotomy by detecting occult metastatic disease in patients with resectable/borderline pancreatic cancer. Methods: We looked at our institutional PET/CT data base incorporating National Oncologic PET Registry (NOPR) with diagnosis of resectable or borderline pancreatic cancer from 2005-2012. Clinical, radiographic, and pathologic follow-up was evaluated, including age, gender, evidence of metastatic disease, and initial CA 19–9 levels. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT. The confidence interval was computed using the exact binomial distribution. The effect on the change was evaluated by the multiple logistic regression model. The final model was selected using the backward elimination method. Results: 287 patients with early stage (resectable or borderline) pancreatic cancer who received PET/CT as part of initial staging workup were identified. Upon initial work up (CT + EUS), 62% of patients were considered resectable and 38% were borderline resectable. However, PET/CT findings changed the management in 11.9% (n=34) of patients (95% CI: 0.084 – 0.162). 33 patients were upstaged to stage IV and 1 patient was upstaged to stage III. Median time from CT to PET/CT was 5 days. Metastatic lesions were confirmed with biopsy in 21 patients. The proportion in the change in treatment plan is significantly higher in patients who were borderline resectable (p=0.005; OR=2.94; 95% CI: 1.38 – 6.26). In 204 patients who were taken to surgery, 17.7% (n=36) were found to have metastatic disease intraoperatively. Conclusions: PET/CT helped improve detection of occult metastases, ultimately sparing these patients a potentially unnecessary operation. The role of PET/CT scan should be validated in prospective study.
First-line gemcitabine, oxaliplatin, and l-asparaginase chemotherapy followed by involved field radiation in stage IE/IIE extranodal NK/T-cell lymphoma.
Authors: Z. j. Xia, Z. h. Wang, S. Li, X. q. Chen, F. h. Wang, F. Xu, N. n. Zhou, Y. Xia, Y. j. Li, K. f. Wang
Journal: Journal of Clinical Oncology (2011)

e18540 Background: Now, there is lack of consensus on treatment of Extranodal NK/T cell lymphoma (ENKTL), and no therapy is considered standard. ENKTL shows a poor response to anthracycline-based chemotherapy, such as CHOP or CHOP-like regimens, because of the frequent expression of a multidrug-resistant P-glycoprotein. Thus, we designed an induce chemotherapy regimen consisted of gemcitabine, oxaliplatin and l-asparaginase(GELOX), which are not affected by P-glycoprotein. In addition, we added involved field radiation. The objective of this study is to investigate the efficacy and safety of GELOX followed by involved field radiation. Methods: From January 2008 to April 2010, 17 newly diagnosed patients with stage IE/IIE ENKTL were frontline treated with GELOX chemotherapy (gemcitabine 1000 mg/m2 intravenous drip on day 1,8; oxaliplatin 130mg/m2 intravenous drip on day 1; and l-asparaginase 5000IU/ m2 intravenous drip on days 1-7) followed by involved field radiation ( radiation 46 Gy to 56 Gy) in Sun Yat-sen University Cancer Center. Results: After treatment of GELOX regimen, there were 12 CRs (70.5%, 12/17) and 5 PRs (29.5%, 5/17), which is a 100% response rate. No patient was disease progression or stable during chemotherapy. All patients achieved CRs after involved field radiation, which is a 100% CR rate. At a median follow-up of 18.6 months (range 5–31), 2 (11.8%) of 17 patients experienced disease progression. the estimated median disease-free survival (DFS) is 30.0 months (95% CI, 26.2 to 38.9). Grades 1 to 2 toxicities were frequent during GELOX, but grades 3 to 4 toxicities were rare (5.9%). Conclusions: In conclusion, GELOX followed by involved field radiation can be a feasible and effective treatment strategy for stages IE to IIE ENKTL.
Comorbidity and the risk of all-cause and prostate cancer–specific mortality in men with unfavorable risk prostate cancer undergoing high dose radiation therapy alone.
Authors: Mai Anh Huynh, Ming-Hui Chen, Jing Wu, Michelle H. Braccioforte, Brian Joseph Moran, Anthony V. D'Amico
Journal: Journal of Clinical Oncology (2016)

207 Background: An association between shortened survival and 6 months of androgen deprivation therapy (ADT) use has been observed in men with moderate to severe comorbidity undergoing external beam radiation therapy (RT) for unfavorable-risk prostate cancer (PC). Whether these men would benefit from treatment with high dose RT alone remains unknown and was explored. Methods: Between October 1997 and May 2013, 7533 men with T1-3NxM0 PC were treated with brachytherapy with or without neoadjuvant RT at the Chicago Prostate Cancer Center. We used competing risks and Cox regression multivariable analyses to evaluate whether the risk of PC-specific and all-cause mortality (PCSM, ACM) were increased in men with unfavorable-intermediate or high risk as compared to favorable-intermediate or low risk PC undergoing brachytherapy adjusting for number of comorbidities (diabetes mellitus, myocardial infarction, congestive heart failure), age at and year of brachytherapy, use of supplemental RT, and an RT treatment propensity score. Results: Of 7533 men treated with curative intent 5737 (76.2%), 1470 (19.5%) and 326 (4.3%) had no, 1, or 2 or more comorbidities respectively. After a median follow up of 7.7 years 958 men died, 81 (8.5%) and 877 (91.5%) of PC and other causes respectively. In the no comorbidity subgroup the risk of PCSM (Adjusted hazard ratio (AHR): 2.39; [95% Confidence interval (CI): 1.32 to 4.31]; p = 0.004) and ACM (AHR: 1.25; [95% CI:1.05 to 1.50]; p= 0.013) were significantly increased in men with unfavorable-intermediate or high-risk PC as compared to favorable-intermediate or low risk PC; however, this was not the case in men with 1 or at least 2 comorbidities as shown in the table. Conclusions: Withholding ADT in men with unfavorable-intermediate or high-risk PC and at least 1 significant comorbidity did not appear to increase the risk of PCSM or shorten survival. [Table: see text]
Tumor genomic profiling (TGP) in metastatic colorectal cancer (CRC): Bridging the community and the tertiary cancer center through genomic consultation (GC).
Authors: John M. Kaczmar, Karen S. Gustafson, Yu Ning Wong, Carl J. Minniti, Vijay Krishna Sandilya, John David Sprandio, Yana Chertock, Caitlin Hart, Michael J. Hall
Journal: Journal of Clinical Oncology (2016)

538 Background: TGP of cancers is increasingly accessible to oncologists (MDs) and patients (pts). Despite efforts to provide clinical interpretation and decision support within TGP reports, results are complex and their interpretation remains fraught with uncertainty. In an ongoing pilot, we provide community MDs access to a 50-gene next generation sequencing (NGS)-based TGP assay and expert guidance through remote access to genomic tumor board (GTB) resources via telephone-based GC. Our goal is to explore how access to GTB expertise impacts community patterns of care. In parallel, we examine MDs and pts perceptions of TGP with a focus on awareness and expectations. Methods: MDs from 4 community practices participated. Participating MDs and their pts with metastatic unresectable CRC receiving 2 nd line or beyond chemotherapy provide informed consent and complete baseline and follow-up surveys. Adequate tumor samples are tested with the Fox Chase 50-gene NGS-based TGP assay. All results are presented at a bi-monthly GTB or are reviewed with the GTB chair. MDs have a ~10 min GC by telephone with the PI to summarize findings and convey GTB recommendations. Results: 9 MDs have enrolled 22 pts and TGP has been completed on 15 samples (4 additional in process and 3 insufficient for TGP). Pts report diverse ancestry (24% Hispanic or non-White) and SES (33% income &lt; $25K). To date, all completed TGPs have reported &gt; 1 mutation. Of 11 pts who have received TGP results, 1 has sought consultation at a tertiary center for a clinical trial. Pts with higher education were more aware of TGP (p = 0.05). Most (80%) pts felt TGP would improve their MD’s ability to treat their cancer. Male sex and higher education were associated with stronger belief that TGP will improve life expectancy. Conclusions: A partnership with community MDs to provide TGP and GTB expertise through GC is feasible. Pts exhibit high expectations of TGP, despite limited data to support improved outcomes from TGP-guided treatment. Further research into optimizing partnership between community MDs and tertiary centers is valuable to guide treatment and clinical trial participation based on TGP results.