tbuckley/cabot-search huggingface dataset:
Interobserver and interlaboratory variability of mismatch repair protein expression in ovarian tumors
Authors: D. Coppola, S. Nicosia, J. Lee, J. Kim, J. Schildkraut, S. Narod, R. Sutphen, T. Sellers, T. Pal
Journal: Journal of Clinical Oncology (2009)

e17505 Background: Immunohistochemistry (IHC) for mismatch repair (MMR) protein (MLH1, MSH2, MSH6) expression has been a useful strategy for identifying tumors with MMR deficiency. However, despite its wide use, interpretation of results suffers from poor reproducibility. Methods: To assess inter-observer (IO) and inter-laboratory (IL) variability of MMR protein expression, 41 epithelial ovarian cancer (EOC) samples were arrayed in triplicate for construction of a tissue microarray (TMA). Six slides were made from this donor TMA block, of which 3 were stained at the Moffitt Cancer Center (MCC) and 3 were stained at the University of South Florida (USF), using different lab procedures. IHC for MMR protein expression was performed using the avidin-biotin-complex (ABC) method with appropriate controls. Subsequently, all slides were independently scored for protein expression by two pathologists. The Concordance Correlation Coefficient (CCC) value was computed to evaluate IO and IL concordance, with a value &gt;0.75 indicating excellent concordance. Results: The CCC value for the IO analysis was 0.95 (for MCC-stained slides; 95% C.I.: 0.89–0.98) and 0.85 (for USF-stained slides; 95% C.I.: 0.66, 0.93), indicating excellent concordance. The CCC value for IL analysis was 0.53 (95% C.I.: 0.37–0.66). Conclusions: Our findings demonstrate that variability in IHC protocols may contribute to the interpretation of IHC results. Our data suggest that when pathologists are given the same slide, there is excellent agreement between two observers; however, when the same slides are stained in a separate laboratory using the same method (ABC) but different protocol, there may be considerable disagreement. These findings are of great clinical significance due to the widespread use of IHC as diagnostic, prognostic and therapeutic tools in cancer care. No significant financial relationships to disclose.
Causes of chemotherapy infusion delays: Results of a time study in an academic cancer clinic in the community.
Authors: Ivy Altomare, Lisa Moss, Arif Kamal, Linda Sutton
Journal: Journal of Clinical Oncology (2012)

251 Background: Chemotherapy administration is a complex process involving several steps and checkpoints. Any of these can improve or delay efficiency in patients receiving timely care. We conducted a time study auditing delays to the start of chemo infusion to determine the main causes of treatment delays and identify areas for improvement. Methods: Within the Duke Oncology Network (DON), an outreach network assisting rural cancer clinics with clinical operations, we identified one site for the study. A DON nurse practitioner and chemotherapy nurse analyzed records from 157 patients who received intravenous (IV) chemotherapy from January to March of 2011. We collected data on timepoints from administrative schedules, nurses’ infusion records and faxes to and from the lab and pharmacy, and median times and ranges were calculated. Results: Causes of chemotherapy infusion delays can be investigated through usual patient and operational documentation. Clear and accurate data could be obtained regarding patient arrival times, time seated in infusion chair, time IV access was obtained, times labs were sent/resulted, times chemotherapy drugs were requested/received and times infusions were started. The longest delays generally involved the earlier steps, including from arrival to treatment start (see Table). Surprisingly, a thorough search did not find any literature-based benchmarks for comparison. Conclusions: It is logistically feasible and clinically helpful to conduct a time study of chemotherapy infusion delays by compiling data from timepoints available in infusion records, admin notations and faxed reports. Interestingly, in our study lab and pharmacy turnaround times were not the main cause of delays as initially expected, nor were MD visits. We identified concrete areas for improvement and will use this data to design a plan for administrators, nurses and clinicians to reduce delays to infusion start by 50%. [Table: see text]
Combined irinotecan and cisplatin therapy for extrapulmonary small cell carcinoma (EPSCC).
Authors: K. Nakano, T. Yuasa, N. Nishimura, Y. Mishima, S. Sakajiri, M. Yokoyama, S. Takahashi, K. Hatake
Journal: Journal of Clinical Oncology (2011)

e13007 Background: Extrapulmonary small cell carcinoma (EPSCC) is a relatively rare neoplasm, which has similar pathological characteristics to the small cell lung carcinoma (SCLC). Although EPSCC is recommended to be treated based on the strategy of SCLC in clinic, standard therapeutic guideline has not been established yet. Recently a combined irinotecan and cisplatin (IP) chemotherapy has been demonstrated to be effective in SCLC. In this study we evaluated the effectiveness of IP regimen for the patients with EPSCC. Methods: We retrospectively reviewed treatment outcome of 44 EPSCC patients treated with IP chemotherapy from April 2005 to October 2010 in our institution. Patients were divided into two-stages, limited disease (LD) or extensive disease (ED) according to the SCLC clinical staging. IP regimen consisted of four four-week cycles of 60 mg/m2 of irinotecan on days 1, 8, 15 and 60 mg/m2 of cisplatin on day 1. Results: Median age was 60 year-old (range 26-79) and median follow-up time was 11.3 months. Primary organs were as follows: 5 gastrointestinal, 19 head and neck, 2 upper respiratory tract, 7 genitourinary and 11 unknown primary origin. The patients with LD and ED were 14 and 30 patients, respectively. Thirty patients received IP as a first-line therapy and 13 patients received one or more therapies (6 surgery, 6 radiation therapy and 10 chemotherapy) before IP induction. The patients were treated with a median of 3 cycles (range 1-8). Response rate was 55.0 % and complete response was shown in 3 patients (7 %). Median progression free survival and overall survival were 5.0 months (95 % CI 12.3-16.9) and 14.6 months (95 % CI 12.3-16.9), respectively. One-year OS rates were 67.2 %. Although Grade 3-4 hematologic and non-hematologic adverse events were seen in 30 patients (68.2 %) and in 18 patients (40.9 %), respectively, no patients died of adverse events. Conclusions: Our retrospective study suggests that an IP regimen is effective and feasible and therefore it might be an effective treatment option for EPSCC.
Prognostic impact of immunohistochemical expression of Ki-67 in patients with advanced gastric cancer who underwent curative resection.
Authors: S. Sym, J. Hong, E. Cho, W. Lee, M. Chung, S. Ha, Y. Park, J. Park, J. Lee, D. Shin
Journal: Journal of Clinical Oncology (2011)

19 Background: Ki-67, tumor proliferation marker, is an important prognostic factor in a variety of cancers. In the present study, we investigated the prognostic value of immunoexpression of Ki-67 in patient with gastric cancer who underwent curative resection. Methods: We retrospectively analyzed 241 patients who had undergone curative gastrectomy at Gachon University Gil Hospital between January 2008 and July 2009. Ki-67 proliferation index (PI) by immunohistochemistry on formalin-fixed, paraffin-embedded material and the other clinicopathologic variables were evaluated by univariate and mulvariate analysis. Results: The median follow-up from surgery was 12 months (range, 0.5-26.7 months) and mean recurrence-free survival was 23 months (95% confidence interval, 21.8-24.1 months). The mean Ki-67 PI was 40% (range, 5-90%). No significant correlation was found between Ki-67 PI and other clinicopathologic variables including histologic grade and pathologic TNM (pTNM) stage. Univariate analysis revealed that significant prognostic factors of recurrence-free survival included age, preoperative serum albumin, pre-operative hemoglobin, surgery type, pTNM, histologic grade, lymphatic vessel invasion, peri-neural invasion, and Ki-67 PI. In the multivariate analysis besides pTNM (p=0.046), lymphatic vessel invasion (p=0.024), and surgery type (p=0.047), Ki-67 PI (p=0.005) also remained as an independent prognostic factor of recurrence, whereas the other factors lost its prognostic value. Conclusions: Our results suggest that high Ki-67 PI is independent, poor prognostic factor of recurrence in patient with gastric cancer who underwent curative resection. No significant financial relationships to disclose.
Comparison of survival outcome of concurrent GnRH agonist plus tamoxifen to that of sequential adriamycin and cyclophosphamide chemotherapy plus tamoxifen in premenopausal, lymph node-negative, hormone-responsive, HER2-negative, T1-2 breast cancer patients.
Authors: Guiyun Sohn, Sei-Hyun Ahn, Hee Jeong Kim, Byung Ho Sohn, jong Won Lee, Beom Seok Ko, Jong Han Yu, Yura Lee, Sae Byul Lee, Seunghee Baek
Journal: Journal of Clinical Oncology (2015)

137 Background: The purpose of this study was to compare treatment outcomes between gonadotropin-releasing hormone (GnRH) agonist plus tamoxifen and adriamycin and cyclophosphamide (AC)-containing chemotherapy plus tamoxifen in hormone-responsive, premenopausal, node-negative, breast cancer patients. Methods: Among 7278 breast cancer patients who were diagnosed as breast cancer at Asan medical center, Seoul, Korea, 994 premenopausal women with node-negative, hormone receptor-positive, HER2-negative, T1-2 breast cancers were included in this retrospective cohort study: A median follow-up was 7.4 years (range, 0.5-11.4 years). 608 patients (61.2%) were treated with GnRH agonist together with tamoxifen, and 386 patients (38.8%) were treated with AC-containing chemotherapy with tamoxifen. The propensity score matching and inverse probability weighting was applied to original cohort based on patients’ age, operation method, nuclear and histologic grade, estrogen receptor and progesterone receptor positivity, T stage, Her2 positivity, and p53 positivity. In final analysis, 260 patients for each treatment arm were included. Results: In propensity matched cohorts (n = 520), a total of 34 patients had recurrence. There were 5 cancer-specific deaths and 12 overall deaths among total 520 patients. There were no survival differences for recurrence-free survival (p= 0.306), cancer-specific survival (p= 0.212), and overall survival (p= 0.102) between the two treatment groups. After applying inverse probability weighting, there were no survival differences for recurrence-free survival (p = 0.522), cancer-specific survival (p= 0.154). However, GnRH agonist with tamoxifen arm showed better overall survival than AC chemotherapy with tamoxifen arm (p= 0.021). Conclusions: Adding GnRH agonist to tamoxifen is a reasonable alternative to adding AC chemotherapy to tamoxifen in premenopausal, hormone-responsive, HER2-negative, lymph node-negative, T1-2, breast cancer patients.
The effect of insurance and ethnicity on healthcare access and health behaviors: A Childhood Cancer Survivor Study (CCSS)
Authors: J. N. Casillas, S. M. Castellino, M. M. Hudson, A. C. Mertens, J. Whitton, S. L. Brooks, L. K. Zeltzer, A. Ablin, L. L. Robison, K. C. Oeffinger
Journal: Journal of Clinical Oncology (2005)

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An observational study evaluating the expression of HER2 (1+, 2+, and 3+) with HLA A2/A3+ in gastric adenocarcinoma patients.
Authors: Ashis Patnaik, Shyam Parvatini, Shalabh Sachdeva, Gavin S. Choy, Akhilesh Sharma, Palepu Jagannath
Journal: Journal of Clinical Oncology (2016)

18 Background: Gastric cancer remains a major health issue and results in 800,000 annual deaths worldwide. Despite approximately 50% of the gastric and gastroesophageal (GE) junction adenocarcinomas are diagnosed with resectable disease, 40% of disease recurrence is observed in 24 months. While trastuzumab has shown to increase overall survival in HER2 IHC3+ metastatic disease, no current therapies are available for low expressing, or IHC 1+ or 2+ patients. NeuVax (nelipepimut-S) is an immunogenic peptide epitope derived from the extracellular domain of HER2/nu protein administered in combination with rhGM-CSF. NeuVax binds to HLA-A2 and A3 on tumor and antigen presenting cells (APC) and elicits a proliferation of CD8+ (cytotoxic) T-cell immune response against HER2 expressing cancer cells. A proof of concept clinical study will be conducted to assess the effectiveness of nelipepimut-S to prevent recurrence and increase disease free survival in gastric cancer patients with all levels of HER2 expression with HLA A2+/A3+. This prospective observational study was undertaken to estimate the HLA A2/A3+ and HER2 expression status in the Indian population. Methods: Tumor tissue samples from gastric or GE junction adenocarcinoma patients were collected from S. L. Raheja Hospital, Mumbai, India. A serum sample was collected for HLA testing by quantitative PCR. IHC (DAKO, 1:600 dilution) was employed for detection of HER2. All patients were consented for the study. Results: Of the 50 patients evaluated, 12 (24%) were positive for HER2 (1+, 2+, 3+) with HLA2/A3 alleles, meeting the defined projected clinical protocol population of all levels of expression of HER2 and HLA A2+ and/or A3+. Of the 12 patients, 9 (75%) and 3 (25%) expressed HLA A2 and A3, respectively, with no patient demonstrating HER2 3+ expression. Conclusions: Results from this prospective observational study suggest patients with gastric and GE junction adenocarcinoma have HLA A2+ and/or A3+ expressing tumors with mostly HER2 1+, 2+ expression. The estimated incidence of HER2 3+ expression in this population may be limited by size of current study. Results will inform the screen failure rate of the planned Phase 2 clinical study.
Survival trends of 89,543 patients with metastatic colorectal cancer: A population-based analysis.
Authors: Ulrich Guller, Ignazio Tarantino, Anthony W. Castleberry, Lukas Brugger, Dieter Koeberle, Thomas Cerny, Ricardo Pietrobon, Christopher Mantyh, Mathias Worni
Journal: Journal of Clinical Oncology (2013)

476 Background: Metastatic colorectal cancer remains among the most common causes for cancer death and is a major public health problem. While overall survival improvements have been achieved in clinical trials, it is unknown how much this progress translated into increased survival on a population-based level. Methods: The SEER (Surveillance Epidemiology and End Results) registry was queried from 1988 to 2008. Patients with metastatic colorectal cancer were included. Multivariable adjusted Cox proportional hazards regression analyses were used. Results: In total, 89,543 patients were included. Median age was 67.1 years, 47.2% were female, 79.7% Caucasian. Median overall survival was 11 months, which increased from 8 months in 1988 to 14 months in 2008 (75% increase). In patients &lt;= 65 years, overall survival increased from 9 months in 1988 to 20 months in 2008 (122% increase), in patients above 65 years from 7 months in 1988 to 9 months in 2008 (29% increase). In Cox proportional analyses, later year of treatment (hazard ratio=HR: 0.973 per year [95% CI: 0.972-0.975], p&lt;0.001), tumor location in the rectum (HR: 0.72 [95% CI: 0.71 - 0.74]; p&lt;0.001), married civil status (HR: 0.85, [95% CI: 0.84 - 0.86]; p&lt;0.001), and cancer-directed surgery (HR: 0.44, [95% CI: 0.43 – 0.45]; p&lt;0.001) were associated with better overall survival, while patients above 65 years (HR: 1.48, [95% CI: 1.46 - 1.51]; p&lt;0.001) and African-Americans (HR: 1.08, [95%CI: 1.06 - 1.11], p&lt;0.001) had worse survival. Conclusions: Tumor location in the rectum, married civil status and cancer-directed surgery are associated with significantly improved overall survival while elderly and African-Americans have worse outcomes. Moreover, a statistically significant and clinically relevant overall survival increase from 1988 to 2008 was found for metastatic colorectal cancer patients. However, most progress is observed in patients aged below 65 years, while the overall survival increase in the elderly is modest. Further studies among elderly patients assessing the reasons for the lack of a parallel survival increase are warranted.
Pattern of relapse in 412 cases of locally advanced breast cancer (LABC) from a single centre in India
Authors: V. Raina, K. Medhi, S. V. Deo, N. K. Shukla, G. K. Rath
Journal: Journal of Clinical Oncology (2008)

12012 Background: Breast cancer is now the commonest cancer in many parts of India and the incidence varies from 12 to 31/100,000 and is rising. Locally advanced breast cancer (LABC) continues to present a challenge due to its poor prognosis. The aim of this study is to study the pattern of relapse and survival of these patients. Methods: This analysis was done of LABC patients who had received combined modality treatment composing of FEC protocol, with MRM and locoregional radiotherapy followed by adjuvant hormonal treatment over a period of 10-years from January 1995 to December 2004. The end points were relapse and overall survival. Follow up was done till June 2007. Results: A total of 609 patients were studied which comprised 26% of our new patients. Four hundred and twelve patients completed standard combined modality treatment. A total of 173 patients (42%) developed relapse. Median age in these patients was 47 years (range 25–83) and premenopausal patients constituted 48%. Local (chest wall) relapse was seen in 7.5%, regional relapse (ipsilateral axilla, supraclavicular fossa) in 3.0%, systemic relapse in 27.4%, locoregional and systemic relapse together in 4.1%. Contralateral (metachronus) breast cancer developed in 1.5%. Lung (10.4%) was the commonest site of systemic metastasis followed by bones (8.0%), liver (7.3%), brain (5.3%) and others (0.5%). Median time to systemic relapse was 20 months. Median overall survival in patients who developed systemic relapse was 36 months and 55 months in those who developed locoregional relapse. However, median survival in all patients (412) has not been reached. Conclusion: Systemic relapse is a major problem and highlights the poor prognosis in these patients with LABC. No significant financial relationships to disclose.
Highmark and Allegheny Health Network: Partners in Quality Oncology Practice Initiative (QOPI) measures automation reporting.
Authors: Kyle Bird
Journal: Journal of Clinical Oncology (2014)

41 Background: ASCO’s QOPI Participation and Certification processes pose a daunting operational task for oncology practices nation-wide. The standardization and quality improvement initiatives required for Certification involve multiple constituents and often a longitudinal approach to quality and operations management. The human resources required for biannual abstraction can be burdensome given strained resources in an increasingly complex reimbursement environment. Allocating staff for retrospective medical record review requires a steep QOPI learning curve and time away from the clinic. The Allegheny Health Network and Highmark, the Nation’s tenth largest insurer, have partnered to create a monthly QOPI measures automation report which alleviates the burden of a purely human resource-based abstraction methodology. Additionally, 100% of Highmark insured, Allegheny Health Network QOPI qualifying patients are included in a monthly report to allow for near real-time clinical decision support. Methods: A multidisciplinary team was assembled with clinical and administrative representatives from Highmark and Allegheny Health Network. The team worked together in phase I of the project for over eight months to review and select specific QOPI measures that could be tracked through a custom-built, claims processing algorithm. Results: Initial data analysis included over seventy-five automated QOPI measures that would be able to be tracked and trended on a monthly basis – populated from Highmark claims data. The monthly report allows for a larger sample size with data tracking across all QOPI domains and disease sites. The multidisciplinary team has moved on to phase II of the project which will include sensitivity analyses and data refinement. Conclusions: QOPI measures automation is possible through an evolving relationship demonstrated through this unprecedented payer/provider initiative. While some of the QOPI reporting measures could be automated, human resources will still be required for annual abstraction in the on-going QOPI Certification phase. Once refined, automated measures will need to be verified to note changes in claims data and clinical documentation.
Molecular mechanisms underlying the synergistic interaction of the novel anticancer drug celandine with gemcitabine in preclinical models of pancreatic cancer.
Authors: N. Funel, E. Giovannetti, M. Del Chiaro, L. Pollina, F. Mosca, G. Peters, D. Campani, U. Boggi
Journal: Journal of Clinical Oncology (2011)

233 Background: Celandine (Ukrain) increased median survival in combination with gemcitabine compared to gemcitabine alone (10.4 vs. 5.2 months; p&lt;0.001) in unresectable PDAC (Gansauge et al.; Langenbecks Arch Surg 2002). There is compelling evidence that gene transcripts of determinants of gemcitabine activity could be used to tailor PDAC chemotherapy (Giovannetti et al., Cancer Res 2006). Methods: In vitro studies were performed in two ATCC cell lines (PL45 and Mia PaCa-2) and two primary cell cultures obtained from PDAC patients who underwent surgical resections (PPTCC78 and PPTCC109). Cells were treated with celandine at IC 50 concentration levelsfor 48 h. The total RNA extraction was performed with TRIzol protocol. All the amplifications were carried out with normalization of gene expression against the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) housekeeping control gene, and the quantitation of gene expression was performed using the direct ratio, the standard curve method and the ΔΔCT calculation, in which the amount of target, normalized to the endogenous control and relative to the calibrator (untreated control cells) was calculated as 2 (-ΔΔCt) . Results: Celandine positively modulates the expression of hENT1 mRNA in all PDAC cell cultures treated with IC50 (p&lt;0.001). The 2 (-ΔΔ Ct) analysis revealed a mean increase of 2.8-fold (p=0.001) with respect to untreated control cells. In PL45 and Mia PaCa-2 cells celandine positively affects mRNA expression of dCK gene as well. Conclusions: To date a few options based on gemcitabine are available for treatment of PDAC. Most gemcitabine-based chemotherapy regimens resulted in a very limited disease control, and studies attempting to widen the therapeutic armamentarium against this disease are warranted. Based on the previous clinical data the celandine-gemcitabine combination appears a promising regimen and the results of the present study provide the experimental basis for the further clinical testing of the celandine-gemcitabine schedule in PDAC patients. No significant financial relationships to disclose.