tbuckley/cabot-search huggingface dataset:
The significance of p53 and Ki-67 expression rate in adenoma and adenocarcinoma of the stomach.
Authors: I. Baek
Journal: Journal of Clinical Oncology (2011)

32 Background: Endoscopic submucosal dissection (ESD) is used for the treatment of gastric adenoma as well as early gastric cancer. Gastric adenoma is a well-known precursor of gastric cancer. The aim of this study is to investigate the expression degree of p53 and Ki-67 in gastric adenoma can predict progression to gastric cancer. Methods: We analyzed p53 and Ki-67 expression degree in the tumor tissue of 16 gastric adenoma patients treated by ESD and 11 early gastric cancer patients treated by subtotal gastrectomy at Kangnam Sacred Heart Hospital of Hallym University between November 2008 and May 2009. According to the fraction of stained nuclei in tumor tissue, expression degree was classified as &lt; 10% = negative, 10%∼33% = 1+, 34%∼66% = 2+, &gt; 66% = 3+. Results: Mean age was 65.1 ± 11.5 years and mean tumor size was 33.7 ± 20.2mm. Among 16 gastric adenoma patients, low-grade dysplasia were 11 and high grade dysplasia were 5. p53 positivity was not different between gastric adenoma and gastric cancer, but Ki-67 positivity was significantly different between adenoma and cancer (p &lt; 0.05). In addition, Ki-67 positivity was increasing tendency as the pathology progress from low grade dysplasia to cancer. Conclusions: Ki-67 positivity grade seems to be correlated with malignancy. High Ki-67 positivity in gastric adenoma can predict progression to gastric cancer. Even if endoscopic biopsy showed low grade dysplasia, additional ESD should be preferentially considered in lesions with high Ki-67 positivity. No significant financial relationships to disclose.
Inflammatory bowel disease in patients with prostate cancer treated with radiation.
Authors: Matthew Maxwell Gestaut, Gregory P. Swanson
Journal: Journal of Clinical Oncology (2016)

15 Background: Inflammatory bowel disease (IBD) has long been considered a risk factor for increased bowel toxicity from radiation therapy (RT); however, minimal evidence exists for patients with prostate cancer (PC) and IBD. Methods: The tumor registry was queried for patients with both IBD and PC from 2000-2010. A chart review was conducted for patients who received RT for PC. All patients carried the diagnosis IBD as defined by either Crohn’s disease or ulcerative colitis. RT specifics and radiation toxicity (acute and late) data were collected. Results: Eighteen patients met the inclusion criteria for PC and IBD diagnoses with radiation therapy treatment. Twelve were treated with external beam radiation therapy (EBRT), and 6 were treated with low dose rate (LDR) brachytherapy. Average length of follow-up was 12 years (median 9.54, range 0.42-19.9). Most patients had well controlled baseline bowel function on medical management. Twenty-two percent were in remission from IBD without any form of treatment; 56% were actively taking 5-ASA; 17% were prescribed prednisone; and 6% were taking Remicade. Sixty percent of patients (9/15) reported grade 0 (G0) diarrhea at baseline prior to radiation therapy. Forty percent (6/15) suffered grade 1 (G1) diarrhea at baseline. No baseline proctitis existed. Two patients reported ostomy prior to radiation. Following radiation treatment, 78% (14/18) of patients experienced G0 diarrhea while 22% (4/18) reported G1 diarrhea. No patients suffered from greater than G1 diarrhea. Sixty-seven percent (12/18), 17% (3/18) and 17% (3/18) of patients experienced G0, G1, and G2 proctitis, respectively. No patients suffered post-radiation stricture formation. All patients with G2 proctitis following RT received 3dCRT. Conclusions: No available published data explores RT for patients with PC and IBD. This retrospective review offers valuable insight into appropriate counseling for a rare patient subset. EBRT was associated with improvement in late G1 diarrhea rates. Grade 2 proctitis was only encountered among 3dCRT patients. No post-radiation stricture or ostomy placements occurred. Our findings suggest that IBD patients experience minimal toxicity with IMRT-based radiation therapy.
Clinical outcome in patients with metastatic colorectal cancer harboring KRAS p.G13D mutation treated with cetuximab.
Authors: H. Bando, T. Yoshino, E. Shinozaki, S. Yuki, T. Nishina, S. Kadowaki, K. Yamazaki, K. Tsuchihara, S. Fujii, T. Yamanaka
Journal: Journal of Clinical Oncology (2011)

448 Background: Metastatic colorectal cancer patients with KRAS codon 12 or 13 mutated tumors are presently excluded from treatment with cetuximab (Cmab). On the other hand, a few patients who have mutated KRAS status occasionally respond to Cmab. The tumors of those patients predominantly had codon 13 mutation, and all codon 13 responder have mutation of p.G13D. We now compared the efficacy of Cmab among patients with p.G13D- mutant, other KRAS mutant and KRAS wild-type colorectal cancer. Methods: The patients from 9 Japanese institutions were retrospectively collected and analyzed. All patients were refractory to fluoropyrimidine, oxaliplatin and irinotecan, and were treated with Cmab and irinotecan combination regimen. Response rate (RR), progression-free survival (PFS) and overall survival (OS) were calculated respectively according to KRAS status. Results: Ninety four patients were treated with combination therapy. Among 94 cases, 7 cases were p.G13D-mutant KRAS, 23 cases were other mutant KRAS and 63 cases were wild-type KRAS. Baseline characteristics by each subset were well-balanced. While one partial response (PR) and 4 stable diseases (SD) cases were found in 7 p.G13D-mutated cases, no PR was found in other KRAS mutated cases. Median PFS of the patients with p.G13D-mutant, other KRAS mutant and KRAS wild-type were 4.5 months (95%CI 1.7-), 2.3 months (95%CI 1.9-4.3), 4.6 months (95%CI 3.5-6.5) respectively. And median OS of the patients with p.G13D- mutant, other KRAS mutant and KRAS wild-type were 9.3months (95%CI 8.5- 11.8), 7.4 months (95%CI 4.5-9.4), 12.2 months (95%CI 8.7-19.8) respectively. Although statistical significance was not found between the two mutated groups, there are trends that the patients with p.G13D-mutant may have received better clinical benefits from Cmab than the patients with other KRAS mutant. Conclusions: Cmab may have therapeutic benefit in the patients with KRAS p.G13D-mutant colorectal cancer although further evaluation is warranted. No significant financial relationships to disclose.
Expression patterns of gpNMB in breast cancer (BC): Retrospective evaluation of tumor tissue from the phase II EMERGE study.
Authors: Denise A. Yardley, Michelle E. Melisko, Andres Forero, Rebecca G. Bagley, Joshua Zhang, Linda T. Vahdat
Journal: Journal of Clinical Oncology (2015)

129 Background: Glycoprotein NMB (gpNMB) is an internalizable transmembrane protein overexpressed in ~20% of BC. gpNMB promoted BC metastases in a murine model and is a poor prognostic marker in BC patients (pts) (Rose 2010). Glembatumumab vedotin (GV, CDX-011) is a novel antibody-drug conjugate targeting gpNMB+ cancer cells with the potent cytotoxin monomethyl auristatin E. In a Phase I/II and in the Phase II EMERGE study, GV was well-tolerated (treatment-related toxicity included rash, neutropenia, and neuropathy) with promising activity in gpNMB+ BC tumors including TNBC. In EMERGE, GV vs. investigator’s choice chemotherapy, demonstrated an objective response rate of 30% (7/23) vs. 9% (1/11) in pts with tumor gpNMB overexpression (gpNMB in &gt; 25% of tumor cells); 18% (5/28) vs. 0% (0/11) in TNBC; and 40% (4/10) vs. 0% (0/6) in gpNMB-overexpressing TNBC. Improvements in progression-free survival (hazard ratio (HR) = 0.11) and overall survival (HR = 0.14) in gpNMB-overexpressing TNBC were noted. Methods: This retrospective analysis of the EMERGE study examined frequency of gpNMB overexpression by various baseline and disease characteristics. Tumors were centrally assessed by immunohistochemistry (IHC) and included data for 328 pts. Results: Tumor gpNMB overexpression was present in 21% (69/328) of screened and 40% (38/96) of TNBC pts. gpNMB overexpression was consistent in progesterone, estrogen, or HER2+ expressing tumors at rates of 12-15%. gpNMB overexpression was not observed among 17 lobular tumors, but was present in 21% (57/270) of ductal tumors. gpNMB overexpression was seen across organ sites, including lung (43%, 3/7), lymph node (31%, 12/39), chest wall (23%, 3/13), breast (21%, 44/209), bone (13%, 1/8), and liver (13%, 3/24). There were no apparent differences in gpNMB overexpression by age, race or disease setting (early vs. advanced) at tissue collection. Analysis is ongoing to determine if prior treatments may upregulate gpNMB expression. Conclusions: gpNMB overexpression in BC, especially in TNBC, appears consistent in archival primary and/or metastatic BC, regardless of age. A randomized multicenter study of GV in gpNMB overexpressing metastatic TNBC (METRIC) is ongoing. Clinical trial information: NCT01156753.
Determinants of capecitabine efficacy in metastatic breast cancer: The role of thymidine phosphorylase
Authors: C. Andreetta, F. Valent, G. Pascoletti, R. Sottile, A. M. Minisini, S. Russo, G. Fasola, S. Pizzolitto, C. Di Loreto, F. Puglisi
Journal: Journal of Clinical Oncology (2008)

1068 Background: Capecitabine (C) is an orally bioavailable prodrug that is converted to 5-fluorouracil in several enzymatic steps, the last of which is mediated by thymidine phosphorylase (TP). TP is expressed at high levels in over 50% of breast cancer (BC) specimens and elevated levels of TP have been hypothesized to predict therapeutic effect of C. Our study aimed at evaluating the potential relationship between immunohistochemical TP expression and benefit from C in terms of time to progression (TTP) in patients (pts) with metastatic BC. Methods: We retrospectively reviewed biopsies of 61 pts with BC treated with at least 3 cycles of C as single agent for metastatic disease, performing immunohistochemistry for TP and other biological markers. All patients received C 1,000 mg/m2 bid days 1 to 14 every 21 days. TTP was defined as the time between the beginning of therapy with C and disease progression or last follow-up. The following variables were analyzed as potential determinants of benefit from C: TP expression; ER and PgR status; HER2 status; MIB-1 expression; Performance Status (PS) at the beginning of C treatment; stage at diagnosis; grade; presence of visceral metastases at the beginning of C treatment; therapies received before C. Results: Overall, median TTP was 6.5 months (range 1.4–33). On multivariate analysis, ER status [hazard ratio (HR) for progression = 0.31, 95% CI 0.15–0.64, p = 0.002], presence of visceral metastases at the beginning of C treatment (HR = 2.30, 95% CI 1.21–4.39, p = 0.01), and C as first or second line treatment (HR = 2.28, 95% CI 1.21–4.32, p = 0.01) independently predicted TTP. TP was highly expressed in 34 out of 61 cases (55.7%). In the subgroup of patients with TP expressing tumour, TTP was significantly longer in pts that received anthracyclines and taxanes before C (median TTP 7.5 vs. 3.3 months, p=0.01, log-rank test). Similarly, pts with a TP-positive tumour showed a longer TTP if they received taxanes before C than pts with TP-positive tumour who did not receive this treatment (7.3 vs. 3.4 months, p=0.03). Conclusions: These data provide further evidence that TP expression in BC could represent a biomarker of sensitivity to C treatment. Prospective studies with translational approach are desirable to confirm the predictive and prognostic role of TP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche
Dose escalated CHOP + etoposide and repetitive autologous stem cell transplantation (MegaCHOEP) with and without rituximab for primary treatment of aggressive NHL
Authors: B. Glass, M. Kloess, A. Engert, W. Berdel, B. Metzner, L. Trümper, M. Loeffler, M. Pfreundschuh, N. Schmitz
Journal: Journal of Clinical Oncology (2005)

6654 Background: The role of high dose chemotherapy (HDT) +/- Rituximab (R) in primary treatment of aggressive NHL is still controversial. Methods: Patients at an age of 18 to 60 years and elevated LDH at diagnosis received 4 courses of dose escalated CHOP + Etoposide +/- R(MegaCHOEP) in a dose escalation trial (primary endpoint: time to treatment failure). Cycles 2 to 4 were followed by autologous SCT. At dose level 3 (DL3) cumulative doses of drugs were as follows: C 19.5 g/m2, H 280 mg/m2, O 8 mg, E 5.04 g/m2 P 2000 mg. In a further step, six cycles of rituximab (375 mg/m2) were added: one dose of R prior to each cycle of chemotherapy and two additional doses 3 and 6 weeks after the last cycle of chemotherapy, respectively. Results: From July 1999 to February 2003, 51 pts were enrolled at DL3, and 89 pts were enrolled at DL3R. There was a higher percentage of pts with ECOG performance status > 1 at DL3 (42.9%) than at DL3R (19.7%, p = 0.012) and with IPI high risk at DL3 (34.3%) than at DL3R (12.7%, p = 0.029). We observed significant differences the percentage of pts receiving the complete program of chemotherapy (DL3:91%, DL3R 71%; p=0.017), but no significant differences in dose intensities of C or E. There were no relevant differences in mobilization of stem cells, non-hematologic toxicity or hematopoietic recovery between treatment groups. After a median observation times of 29 months (DL3) and 18 months (DL3R), OS did not differ significantly with 68% (without R) and 74% (with R) at two years, respectively. In univariate analysis a trend to better freedom from treatment failure in patients receiving DL3R as compared to DL3 with 70% vs 53% at 2 years (p = 0.076) was seen. We performed a multivariate risk factor analysis including LDH, performance status, stage and treatment group. Relative risk of treatment failure of MegaCHOEP without rituximab was 1.5; this, however, was not statistically significant (p = 0.23). Conclusions: Combination of rituximab with repetitive high dose chemotherapy and SCT is feasible and safe. In contrast to other patient groups, the effect of adding of rituximab to high dose chemotherapy in young high risk patients seems more limited. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Amgen, Hoffmann- La Roche
Pilot experience with adjuvant FOLFIRI with or without cetuximab in patients with resected stage III colon cancer: NCCTG Intergroup N0147.
Authors: J. Huang, D. J. Sargent, M. R. Mahoney, A. F. Shields, E. Chan, R. M. Goldberg, S. Gill, M. S. Kahlenberg, J. T. Quesenberry, T. C. Smyrk, A. Grothey, F. Sinicrope, S. G. Nair, S. R. Alberts
Journal: Journal of Clinical Oncology (2011)

3522 Background: Irinotecan (CPT-11) has antitumor activity against metastatic colorectal cancer alone or with 5-fluorouracil (5FU)/leucovorin (LV). Two arms with CPT-11, 5FU, and LV (FOLFIRI) +/- cetuximab (Cmab) were originally included in N0147. However, after CALGB 89803 (J Clin Oncol 25:3456, 2007), PETACC-3 (J Clin Oncol 27:3117, 2009), and Accord02 (Ann Oncol 20:674, 2009) showed no benefit to a CPT-11 combination in adjuvant therapy, the CPT-11 arms of N0147 were discontinued. We report the outcomes for patients given FOLFIRI and FOLFIRI+Cmab (F-Cmab). Methods: Patients with resected stage III colon cancer were randomized to one of 6 arms including 12 biweekly cycles of FOLFIRI (CPT-11 180 mg/m2 d1 with LV 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1,2) without or with Cmab 400 mg/m2 d1 cycle 1, then 250 mg/m2 d1, 8. Primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Results: 146 evaluable patients (Arm B-106, Arm E-40) were enrolled; median follow-up was 59.6 months (range 1.5-72). In pts with wtKRAS (vs mt) cancers, trends toward improved DFS (HR=0.6 [95% CI 0.3-1.1], p = 0.10) and OS (HR 0.7 [95% CI 0.3-1.5], p = 0.34) were observed. The addition of Cmab improved DFS and OS in the overall group and within wtKRAS patients (Table). Grade >= 3 non-hematologic adverse effects were significantly increased in the Cmab arm (46% vs. 68%, p = 0.02). Conclusions: In this small randomized comparison, trends for improved DFS and OS with the addition of Cmab to FOLFIRI were observed in patients with resected stage III colon cancer patients, regardless of KRAS status. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. Patient outcome. Overall (n=146) wtKRAS (n=95) FOLFIRI F-Cmab HR (95% CI; p*) FOLFIRI F-Cmab HR (95% CI; p*) N 106 40 - 69 26 - 3 yr DFS 67% 87% 0.4 (0.2-0.97; 0.04) 70% 92% 0.3 (0.1-1.02; 0.04) 3 yr OS 84% 92% 0.3 (0.1-1.0;V0.04) 85% 92% 0.3 (0.1-1.5:V0.13) * Score test p value.
Oncologist liaison: Satisfaction and symptoms in cancer long survivors.
Authors: Francisco Javier García Navalón, Rosa Monfort García, Alberto Jacobo Cunquero Tomás, Gerardo Antonio Umanzor Funez, Virginia Palomar Coloma, Vega Iranzo, Ana Blasco, Carlos Camps
Journal: Journal of Clinical Oncology (2014)

251 Background: Each year, the prevalence of cancer long survivors (CLS) increases; defined as a person who after five years of diagnosis and treatment is free from disease. Health problems faced by these patients are different from those in general population. Because of that, our service launched in 2007 the figure of the Oncologist Liaison, which acts as a link, and is responsible for assessing these Patients at Specialty Centers. Methods: 238 questionnaires, answered by CLS, were collected between January 2013 and April 2014. Variables of interest were collected by a 18-item questionnaire, designed to assess the aftermath of treatment, socio-emotional impact and employment impact. To assess the performance, methods of descriptive statistics have been used. Results: 90.6% of CLS believe that Oncologist Liaison improves their quality of life, with a decrease in anxiety in 80% of them. 52% of the patients (124) have residual symptoms, being the most frequent asthenia (27.6%). The most prominent symptoms were neurological, such as insomnia (16.5%), anxiety (17.4%) and depression (12.2%). Musculoskeletal problems included myalgia (29.5%), arthralgia (27.5%) and paresthesias (18.3%). Cancer and its treatment have a great impact in sexuality, affecting the 35% of the patients: 24'6% have sexual appetite loss and 7.5% dyspareunia; 10.5% of the men refer impotence and premature ejaculation 5% of them; 28.5% of the women referred vaginal dryness. Conclusions: First, more than half of our patients presented residual symptoms; reporting 90% of them improvement in quality of life related to surveillance. Second, it is necessary to create in our Medical Oncology Services a professional dedicated to coordinate the scientific and organizational aspects necessary for a good follow-up of CLS.
Improving the quality of care for patients receiving radiation therapy: Increasing the proportion of radiation treatment plans undergoing peer review in Ontario.
Authors: Lindsay Elizabeth Reddeman, Michael Donald Brundage, Sophie Foxcroft, Margaret Hart, Eric Gutierrez, Marissa Mendelsohn, Padraig Richard Warde
Journal: Journal of Clinical Oncology (2014)

136 Background: Peer review of radiation treatment (RT) plans is recognized as an essential component of quality assurance programs in radiation medicine (Marks et al., 2013). The benefits of peer review include: (1) identifying errors that may compromise treatment outcomes, (2) enhancing safety by promoting standardization, and (3) promoting greater attention to detail in RT staff. Current state analysis conducted in 2011 identified considerable variation in the proportion of cases undergoing peer review across Ontario’s 14 cancer centres (Brundage et al., 2013). In 2012, Cancer Care Ontario launched an initiative to ensure all patients receiving radical/adjuvant radiotherapy have the benefit of peer review of their RT plans. Methods: A multi-professional project team was established to conduct site visits to promote peer review at the cancer centres. They also provided guidance on the organization of peer review rounds so that the activity could be incorporated into local workflows. The education, training, methods, and a centralized reporting infrastructure were developed in collaboration with centres over a one year ramp-up phase and patient-level data was available to the centres for audit purposes. The reporting infrastructure enabled reporting of (1) the proportion of cases peer reviewed and (2) the timing of peer review – prior to treatment, &lt;25% dose delivered, &gt;25% dose delivered. Results: Data for each centre is now a key quality metric and is publicly reported (see Cancer System Quality Index at http://www.csqi.on.ca/). The target for year-one of the project (2013-14) – the proportion of cases to be peer reviewed – was set at 50% with the intent that 100% of cases will be peer reviewed within the next two years. In the ramp-up year, the proportion of cases peer reviewed increased across all centres, though high variation still exists between centres. Conclusions: This initiative demonstrates that it is possible to substantially increase peer review activities on a jurisdictional basis. Key success factors include: a dedicated project team, buy-in and confidence in data quality from centres, investment in education and training, and commitment to public reporting.
A phase I study of erlotinib in combination with chemoradiation (CRT) for unresectable, locally advanced non-small cell lung cancer (NSCLC)
Authors: P. C. Hoffman, A. M. Mauer, D. C. Haraf, E. P. Lester, L. L. Szeto, E. E. Vokes
Journal: Journal of Clinical Oncology (2005)

7113 Background: Erlotinib(ER) is an inhibitor of epidermal growth factor receptor tyrosine kinase(EGFR-TK) approved for second line treatment of locally advanced or metastatic NSCLC. Preclinical studies indicate that small molecule inhibitors of EGFR-TK enhance the effects of ionizing radiation. Objective: To determine the maximum tolerated dose of ER that can be administered with standard CRT for NSCLC. Methods: Patients (pts) with unresectable stage III NSCLC enrolled in this 2-arm phase I dose-escalation study. Arm A included CRT with cisplatin(50mg/m2 IV d1,8,29,36), etoposide(50mg/m2 IV d1–5,29–33), chest radiation therapy(RT) (2Gy QD, Total 66cGy) & daily oral ER for 7 weeks followed by docetaxel(75mg/m2 IV Q21d) for 3 cycles. Arm B included induction paclitaxel(200mg/m2 d1) & carboplatin(AUC=6 d1) for two 21-day cycles then CRT with weekly paclitaxel(50mg/m2), weekly carboplatin (AUC=2), RT (2Gy QD, Total 66cGy) & daily ER for 7 weeks. In both arms, the ER dose was escalated from 50 to 150mg/day. Results: Twenty-five pts were enrolled and treated. Patient characteristics: ECOG performance status (0 in 17 pts, 1 in 6 pts, 2 in 1 pt.), median age 62 (range 51–78), gender male 15, female 10. For arm A (n=11), grade 3 toxicities during CRT were: esophagitis(4), thrombocytopenia(2) and pulmonary infiltrate(1). For arm B (n=14), grade 3 toxicities during CRT were: esophagitis(4), thrombocytopenia(1) and bilirubin(1). Grade 3/4 leukopenia was noted in both arms, but was not clinically significant. DLT has not been noted in either arm. Overall responses were (Arm A/B): Partial Response (A3/B6), Stable Disease (A5/B5), Progressive Disease (A2/B2), Not Evaluable (A1/B0). Conclusions: The addition of ER to two standard CRT regimens is feasible and does not appear to increase in-field toxicities. ER plus CRT warrants further examination in a phase II trial. Supported by NCI-P30 CA14599–28 & N01 CM17102–02 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech