tbuckley/cabot-search huggingface dataset:
Phase II study of dose-dense chemotherapy followed by dose-intense erlotinib for initial treatment of metastatic NSCLC.
Authors: L. L. Waller, A. A. Miller, N. P. Streer, J. F. Lovato, W. J. Petty
Journal: Journal of Clinical Oncology (2011)

7601 Background: Erlotinib is an effective treatment strategy for patients with NSCLC. Previous trials have associated clinical benefit with pharmacodynamic outcomes such as the development of rash or diarrhea. Maximizing dosing for each individual patient based on their metabolism of erlotinib may be one method to improve outcomes associated with this drug. This study aimed to establish a safe and effective method for intra-patient dose escalation of erlotinib. Methods: Patients with metastatic NSCLC received docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day1 on a q 2 week cycle for a total of 4 cycles. All patients were given pegfilgrastim growth factor support on day 2. Patients then received erlotinib with initial doses based on current smoking status, 150 mg daily for non-smokers and 300 mg daily for smokers. Erlotinib doses were escalated by 75 mg every 2 weeks until development of grade 2+ non-hematologic toxicity. In the event of grade 2 toxicity, erlotinib was continued at the same dose. In the event of grade 3+ toxicity, doses were held until resolution and restarted after decreasing the dose by 75 mg daily. Results: 45 patients were enrolled from 8/2007 through 1/2011 and enrollment is now completed. Maximal tolerated dose (MTD) of erlotinib achieved ranged from 75 to 525 mg. Maximum doses achieved in smokers was higher than in non-smokers. 91.7% of evaluable patients achieved an MTD prior to being removed from the study. No grade five toxicities or evidence of interstitial lung disease were observed. Preliminary PFS using time to first progression shows a median PFS of 4.6 months (95% CI 3.58 to 5.65). Updated PFS and overall survival will be analyzed and updated in May 2011. Conclusions: A high degree of inter-patient variability exists in erlotinib MTD. Active smokers tolerate a higher dose of erlotinib than non-smokers. The dose-escalation strategy used in this study appears to be safe and effective for individualizing erlotinib dose.
Effect of neoadjuvant pelvic perfusion on symptom control and resection of pelvic recurrent rectal cancer.
Authors: Harold J. Wanebo, Giovanni J. Begossi, Eric Gustafson, James Belliveau
Journal: Journal of Clinical Oncology (2015)

723 Background: Isolated pelvic perfusion (IPP) may improve disease control and facilitate pelvic resection in selected high-risk patients with advanced recurrent rectal cancer by reducing painful tumor burden and lessening chances of recurrence. Methods: IPP was done in 42 patients with locally advanced previously irradiated rectal cancer, 26 as preoperative therapy and 16 for palliation. A comparative larger non-perfused group included 63 patients with pelvic resection only via abdominal sacral resection (ABSR) for recurrent rectal cancer. Isolated pelvic perfusion (IPP) with a pump oxygenator, (temp &gt; 41ºc), delivered sequential (q 10 minutes) chemotherapy:– 5FU (5fluorouracil) 1,500 mg/m 2 , cisplatin/oxaliplatin 100/150 mg/m 2 , mitomycin 10mg/m 2 , for 60 minutes in 42 patients. Results: Palliative IPP in 16 advanced rectal cancer patients resulted in significant relief (1–4 months) of narcotic resistant pain (in 70%). Pre-operative IPP in 26 locally advanced rectal cancer patients achieved a clinical path (CR) in 2 patients, and significant regression in 11 patients rendering them resectable. Seven had RO pelvic resections. Of 6 other patients, 4 refused surgery, 2 were medically excluded. Median survival was 30 months in 7 resected patients (all had RO resections) and 2 were 5-year survivors. This is compared to outcome in 63 patients having pelvic resection alone for recurrence: 57 % had RO resection (median OS = 36 months), 28% had R1 resection (median OS = 15 months) and 15% had R2 resection (marrow invasion) (median OS = 21 months). Conclusions: Neoadjuvant IPP may facilitate resection of advanced or (borderline resectable) recurrent rectal cancer by reducing tumor bulk and identifying therapeutic responders likely to benefit from major pelvic resection while excluding non-responders mostly likely to benefit from non-surgical therapy. The potential to induce regression and facilitate RO resection merits further exploration
Advanced stage breast cancer presentation in African-American patients—A single institution experience
Authors: G. A. Santebennur, N. Palanisamy, A. Gabriel, J. Sanmugarajah
Journal: Journal of Clinical Oncology (2008)

22138 Background: Breast carcinomas appear to be more aggressive in African Americans (AA) than in Caucasians with respect to advanced stage at diagnosis, higher histologic and nuclear grade and less ER positivity. Several studies also reveal that triple negative breast cancer (BC) is more common in AA, especially pre-menopausal patients. An estimated 19,010 new cases of BC are expected to occur among AA women in 2007 nationally and 88% of the BC patients who present to our institution are AA. Methods: Information about age and race of newly diagnosed BC patients from 2002 to 2006 were obtained from our institution's tumor registry and stage, tumor size, hormone receptor and her2neu status were obtained by reviewing the pathology reports. Results: Of the 267 newly diagnosed BC patients, 236 (88.4%) were AA, 22 (8.2%) Caucasians and race unknown were 9 (3%). Eighty nine (33.3%) patients were <50 years of age. Of the 245 patients with known stage: Stage-0 and Stage-I 80 (32.8%), Stage-II 83 (34.0%), Stage-III and Stage-IV 82 (33.6%). Tumor size was known for 210 patients. Size <2cm 85 (40.5%), 2–5 cm 85 (40.5%) and >5cm 40 (19%). Hormonal status was known for 194 patients. ER and/or PR were positive in 128 (66.0%) patients. Her2neu status was available for 155 patients and it was positive in 60 (38.7%). ER/PR/her2neu was negative in 42 patients (27.1%). Of the triple negative patients, 39 (92.7%) were AA, 15 (35.7%) were <50 years of age, 34 (80.9%) presented with Stage-II or higher stage, tumor size was <2 cm in 7 (22.6%), 2–5 cm in 17 (54.8%), >5 cm in 7 (22.6%) and unavailable for 11 patients. Conclusions: As opposed to national averages, our institution data demonstrates a significant proportion of AA patients present with larger tumors, advanced stage at diagnosis and triple negative tumors. Reasons for the late presentation are unclear. Aggressive biology of the tumor and poor adherence to screening may be contributing to this. We do not have data on screening adherence of these patients. Community based screening and education may maximize early detection of breast cancer in these patients. No significant financial relationships to disclose.
Role of KRAS mutation in advanced ovarian cancers treated by targeted medicines in Thailand.
Authors: Thongbliew Prempree
Journal: Journal of Clinical Oncology (2014)

e22072 Background: The treatment of advanced ovarian cancer has been surgery followed by various forms of chemotherapeutic agents. Once the chemotherapeutic agents failed to achieve the response, the option left is rather diamal. Recent advances in targeted medicines along with specific genes study allowed us to study this group of patients. Our objective is to 1) to determineKRAS mutation in all ovarian cancers treated by targeted medicines 2) To compare the response of patients with KRAS mutation versus those without KRAS mutation 3) To modulate the treatment in the presence of KRAS mutation. Methods: 25 cases of advanced and recurred (stage IV) ovarian cancers who had exhausted all chemotherapeutic treatment were included in the study. To select the targetsfor the treatment, we examined the VEGF, EGFR,cKIT and HER2 genes using IHC ( Immunohistochemical) technique with additional DNA study. KRAS mutation was studied by DNA sequencing technique. Treatment targeted medicines used: 13 cases of Bevacizumab+ sunitinib, 4 cases of Bevacizumab+ EGFR TKI, 6 cases of Bevacizumab + Anti-EGFR monoclonal antibody and 2 cases of Bevacizumab+ trastuzumab. Results: 1) KRAS mutations were found in 10 of 25 cases (40%). Types of mutation included; 3 cases of G12D mutation, 4 cases of G12V mutation, 2 cases of G12C mutation and 1 case of G13D mutation. 2) Responses: Those with KRAS mutation showed 3 months response of 3/10 (30%) and those without KRAS mutation showed 3 months response of 9/15 ( 60%). For one year response: Those with KRAS mutation showed 1/10 (10%) and those without KRAS mutation showed 5/15 (33%) one year response. Conclusions: 1) Type of KRAS mutation played no role in achieving response. 2) Cases with KRAS mutation represented the overall poor prognosis. 3) At present, we have been using mTOR inhibitor in order to block PI-3K signal transduction pathway in KRAS mutation patients with some degrees of success.
A UGT1A1 genotype-guided dosing study of irinotecan in metastatic colorectal cancer (mCRC) patients (pts) treated with FOLFIRI plus bevacizumab (BEV).
Authors: Manish Sharma, Giuseppe Toffoli, Angela Buonadonna, Elena Marangon, Blase N. Polite, Sergio Frustaci, Federico Innocenti
Journal: Journal of Clinical Oncology (2014)

562 Background: Dosing based on UGT1A1*28 genotyping has been demonstrated to reduce irinotecan-related adverse events. Previous data (Toffoli et al. JCO, 2010) showed that mCRC pts treated with first-line FOLFIRI tolerated higher doses (310 mg/m 2 for *1/*28; 370 mg/m 2 for *1/*1) of irinotecan than the standard 180 mg/m 2 . The aims of this study (NCT01183494; supported by Eudract 2009-012227-28) were to define the maximally-tolerated dose (MTD) of irinotecan in FOLFIRI plus BEV as first-line therapy in mCRC pts and to determine whether BEV alters irinotecan pharmacokinetics (PK). Methods: Pts were accrued at 3 sites: Chicago (USA), Aviano (Italy), Rome (Italy). In *1/*28 and *1/*1 pts (*28/*28 pts were excluded), irinotecan was administered at an initial dose of 260 mg/m 2 IV every 2 weeks. The dose was escalated to 310 and 370 mg/m 2 if 0/3, &lt;2/6, or &lt;3/10 pts had a DLT (grade 3-4 non-hematologic or grade 4 hematologic toxicity during the first 28-day cycle). MTD was defined as the highest dose at which &lt;4/10 pts had a DLT. 5-FU was administered as a 400 mg/m 2 IV bolus followed by 2400 mg/m 2 IV over 46 hours, plus 200 mg/m 2 leucovorin. BEV was administered at 5 mg/kg IV on day 3 (2 days after irinotecan) and on day 15 (before irinotecan), then every 2 weeks. Irinotecan PK were collected on days 1-3 (in absence of BEV) and on days 15-17 (in presence of BEV). Results: 44 pts (23 *1/*28; 21 *1/*1) were enrolled and 43 were evaluable for DLTs during cycle 1 (Table). Neutropenia and diarrhea were the most common DLTs and were each observed in 5 of 11 (45%) pts with DLTs. The MTD is 260 mg/m 2 in the *1/*28 cohort and at least 310 mg/m 2 in the *1/*1 cohort. In a preliminary analysis of 22 pts, BEV decreased the AUC of SN-38, the active metabolite of irinotecan (p = 0.026 by Wilcoxon matched pairs signed rank test). Conclusions: In first-line therapy of mCRC with FOLFIRI plus BEV, irinotecan doses higher than the standard dose can be safely administered based on UGT1A1 genotype. The impact of this genotype-guided dosing approach on survival will be established in future trials. Clinical trial information: NCT01183494. [Table: see text]
Treatment outcomes of chemotheraphy for advanced gastric cancer with disseminated intravascular coagulation.
Authors: K. Lee, I. G. Hwang, J. Jang, S. H. Park, J. H. Kang, S. Y. Oh, H. Kwon, D. H. Lim, K. Park, S. Lee
Journal: Journal of Clinical Oncology (2011)

e14532 Background: Gastric cancer is also the most common cancer and the second leading cause of death in South Korea. Acute Disseminated intravascular coagulation (DIC) which manifests as a consumptive coagulopathy with severe bleeding, is a rare but severe complication of cancers. But, Advanced gastric cancer (AGC) appears to be one of the cancers which are most frequently associated with DIC. The treatment of cancer-related acute DIC is difficult and most patients die within 1–4 weeks. The key of treatment is the control of the underlying cancers. Effective chemotherapy of the underlying malignancy may be the only way to control acute DIC. We assessed the effect of chemotherapy agents as the primary treatment of AGC with DIC. Methods: Thirty-six patients with histologically proven gastric adenocarcinoma presented with DIC who be treated with chemotheraphy were enrolled for this study from December 1994 to April 2010. DIC was confirmed by Scoring system by Japanese Association for Acute Medicine criteria. Results: Median age was 54 years (range 25-69). The majority of patients was poor ECOG performance status (≥3 : 72.7%). Most common histologic subtype was papillary adenocarcinoma (53.3%). Signet ring cell carcinoma was also 9 patients (30%). The chemotherapy regimens patients received were as follows: 18 (50%) patients were treated with fluoropyrimidine or cisplatin based chemotherapy; 12 (33%) with taxane; 4 (11%) with oxaliplatin and 2 (5.6%) with irinotecan. Median cycle number was 3 (range, 1-10). Dose reduction was done only 20% patients. Response evaluation was done in 22 (61.1%) patients. Overall response rate was 9.1% (partial response 9.1%, stable disease 4.5%, progression 86.4%). Median overall survival was 5.74 months (95% CI: 2.77-8.73 months). Conclusions: Based on our experience, chemotheraphy can be a reliable therapeutic option for AGC with DIC. However it was warranted to evaluate further prospective study.
A molecular prognostic nomogram for resectable pancreatic cancer.
Authors: D. K. Chang, E. K. Colvin, C. J. Scarlett, M. Pajic, M. Pinese, A. J. Gill, E. A. Musgrove, R. Sutherland, J. Kench, A. V. Biankin
Journal: Journal of Clinical Oncology (2011)

154 Background: Defining clinically and biologically relevant phenotypes in other cancers has led to substantial improvements in the overall outcomes, but as yet none have been defined for pancreatic cancer (PC). About 80% of patients with pancreatic cancer succumb to the disease despite curative resection, many of whom within 6 months of surgery. There is a clear need to better define the biology and clinical behaviour of PC. This study aimed to evaluate the potential clinical utility of biologically relevant molecules as prognostic factors in resected PC. Methods: We assessed the relationship of aberrant S100A4 calcium-binding protein expression with survival in a cohort of 372 patients who underwent surgical resection for PC and derived a nomogram using clinicopathologic variables and aberrant expression of S100A4 and S100A2. Results: High S100A4 expression was an independent poor prognostic factor in both the training (n = 76; HR = 5.00, 95% CI = 2.29 – 10.9; p &lt; 0.0001) and validation sets (n = 296; HR = 1.78, 95% CI = 1.29 – 2.46; p = 0.0004). Incorporating previously published data on S100A2, demonstrated that high expression of S100A4 was still an independent prognostic factor. Aberrant expression of these proteins stratified the cohort into three distinct prognostic groups. A preoperative nomogram using only variables that could be measured preoperatively (tumor size and molecular biomarkers), predicted survival better than nomograms derived from using clinicopathologic variables, which are only determined after examination of the resected specimen. Conclusions: Aberrant expression of S100A4 and S100A2 stratifies PC into distinct prognostic groups and improves the accuracy of prognostic nomograms using variables that can be determined preoperatively. The development and application of such nomograms in routine clinical practice has the potential to improve patient selection and as a consequence overall outcomes for PC. No significant financial relationships to disclose.
Patient-reported oncology readmission factors.
Authors: Shreya Kangovi, Tracey L. Evans, Nandita Mitra
Journal: Journal of Clinical Oncology (2012)

48 Background: Reducing the risk of readmissions is an important quality goal for hospitals. Little is known of the perspectives of patients on underlying challenges that may lead to readmission. The objective of this study was to elicit perspectives of readmitted oncology patients on barriers to a successful transition from hospital to home. Methods: As part of a larger survey of readmitted inpatients, a 36-item survey was administered to 197 oncology patients readmitted to the hospital within 30 days of discharge to home. Surveys were administered at The Hospital of the University of Pennsylvania (an urban tertiary care academic medical center) and Penn Presbyterian Medical Center (an affiliated urban community hospital), both located in Philadelphia. Responses were entered in real-time into the electronic medical record (EMR) and used by the care team to address patient concerns and improve quality. Results: 45.2% of readmitted oncology patients reported challenges during the transition from hospital to home which they perceived as contributing to readmission. The most commonly reported transition challenges within the oncology population included difficulty with activities of daily living (ADLs) (17.8%), feeling unprepared for discharge (14.2%) and difficulty adhering to medications (7.1%). 15.2% of patients could not identify any modifiable factor contributing to readmission and reported returning simply because of symptoms from progressive illness. After adjusting for potential confounders (age, gender and severity of illness) using multivariable logistic regression models, uninsured and Medicaid patients were more likely than other patients to attribute readmission to difficulty accessing medications (OR 4.5, 95%CI 1.0, 19.9) and performing ADLs (OR 2.7, 95%CI 1.18, 6.1). Conclusions: Understanding challenges reported by readmitted oncology patients may enable inpatient oncologists to tailor transitions interventions to patient needs. Specifically, ensuring patients are able to perform necessary ADLs, are prepared for discharge and have assistance with medication adherence may help prevent unplanned readmissions. Uninsured and Medicaid patients may require additional assistance with accessing medications and ADLs.
Clinicopathological features of patients with colorectal cancer among <i>KRAS</i> wild type p.G13D and other mutations: Results from a multicenter, cross-sectional study by the Japan Study Group of <i>KRAS</i> Mutation in Colorectal Cancer.
Authors: H. Uetake, T. Watanabe, T. Yoshino, K. Yamazaki, M. Ishiguro, K. Sugihara, Y. Ohashi
Journal: Journal of Clinical Oncology (2011)

3605
Development of an algorithm to identify metastatic prostate cancer in electronic medical records using natural language processing.
Authors: Lauren P. Wallner, Julia R. Dibello, Bonnie H. Li, Chengyi Zheng, Wei Yu, Sheila Weinmann, Kathryn E. Richert-Boe, Debra P. Ritzwoller, Stephen K. VanDenEeden, Steven J. Jacobsen
Journal: Journal of Clinical Oncology (2014)

164 Background: Prostate cancer patients who develop metastases are a difficult population to identify through administrative diagnostic codes, due to their protracted time to metastases, limited survival and the inconsistent use of specific codes. As a result, research that is needed to inform the delivery of high-quality care in this setting is limited. Therefore, the goal of this study was to develop an algorithm, which utilizes EMR data to identify men who progress to metastatic prostate cancer after diagnosis using natural language processing (NLP). Methods: An electronic algorithm was developed to search unstructured text using NLP to identify progression to metastases among men with a diagnosis of prostate cancer between 1992 and 2010 in a large, diverse cohort of men who were part of an ongoing study focused on prostate cancer mortality. A training set of 449 men who were diagnosed as early stage prostate cancer was used for development. Pathology, radiology and clinic notes were searched from diagnosis until death or loss to follow-up. Pathology reports were searched for mention of adenocarcinoma in the metastatic lesion, radiology reports were searched for abnormal findings consistent with metastases, and clinic notes were searched for mentions of increasing pain or narcotic use related to metastases. Each NLP component was validated against manual review of the corresponding records. Results: Of the 449 men in the training set, 40 (8.9%) were found to have metastatic prostate cancer. The majority of cases had evidence of metastases in their clinic notes (98%). Radiology reports identified 18% of cases, and pathology reports identified 5%. Of the 40 cases identified, 25% did not have a corresponding ICD-9 codes for metastatic cancer. However, 7.5% used ADT, 37.5% had increasing oncology visits and 22.5% had rapidly rising PSA levels. Conclusions: Our results suggest that NLP can be used to identify men with metastatic prostate cancer in the EMR more accurately than diagnosis codes alone. The automated identification of patients with metastatic cancer facilitates quality of care research in this setting to ensure the delivery of appropriate and high-quality care.
Multicenter retrospective analysis of clinical predictors of response to sorafenib in patients with hepatocellular carcinoma.
Authors: P. D. Lulla, J. E. Brammer, S. J. Bandeali, G. R. Lynch
Journal: Journal of Clinical Oncology (2011)

e14585 Background: Hepatocellular Carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Phase III trials have shown that sorafenib improves survival over best supportive care in unresectable HCC. However, little is known about which clinicopathological factors predict treatment benefit. Methods: 95 cases of HCC treated with sorafenib from 2006-2010 were reviewed. Demographic, clinical, and laboratory data was obtained upon sorafenib initiation. RECIST criteria were used to assess objective benefit (OB: response and stable disease, SD). The chi-square test was used to determine associations between variables and OB on sorafenib. Log-rank tests were used to compare Kaplan-Meier estimates of overall survival (OS). Multivariate analysis was performed on significant variables. Results: The median age was 58 (26-91 years; 78% male; 38% White, 26% African American [AA]). The median treatment duration was 128 days. 68% were HCV positive, 8% had chronic HBV infection, 55% were Childs-Pugh (CPS) Class A and 45% were Class B/C. 32% had AJCC stage IV disease and 36% had vessel invasion. 34% of patients had an OB (1 CR, 2 PR, 29 SD). Non-AA race (OR 0.27; p=0.02), CPS class A (OR p=0.04), absence of metastasis (OR 0.18; p=0.002), absence of lung metastasis (OR 0.2; p=0.03), and histological grade G1/G2 (OR 0.26; p=0.03) were associated with OB. Median OS for all patients was 6.2 (0.5-42) months. For patients with OB, OS was 10.3 (2.5-42) compared to 5 (0.5-42) months in progressive disease (PD). Patients with OB had a PFS of 7 months. On univariate analysis, the following were associated with worse OS: PD, stage IV disease, AA race, and histological grade G3/G4. On multivariate analysis the following remained poor predictors of OS: PD (HR 2.9; p=0.03), grade G3/G4 (HR 2.2; p=0.05), and AA race (HR 2.9; p=0.03). Conclusions: In this heterogeneous population of patients with HCC, CPS-A, AA race, absence of metastasis, and tumor grade were associated with an OB to sorafenib while AA race, PD, and histological grade independently predicted poor OS. Clinicopathological factors combined with molecular markers may enable clinicians to identify HCC patients more likely to benefit from sorafenib.