tbuckley/cabot-search huggingface dataset:
PDL1 status in muscle-invasive urothelial carcinoma in the context of neoadjuvant cisplatin-based chemotherapy.
Authors: Jen-Jane Liu, Alexander S Baras, Nilay M Gandhi, Gunes Guner, Enrico Munari, Sheila Faraj, Janis M. Taube, Mark Schoenberg, Noah M. Hahn, Charles G. Drake, George J. Netto, Trinity Bivalacqua
Journal: Journal of Clinical Oncology (2015)

300 Background: Although complete and partial response rates to cisplatin-based neoadjuvant chemotherapy (cNAC) are 40-50% in patients with muscle-invasive urothelial carcinoma (MIUC), post-cystectomy cancer specific survival (CSS) for patients who fail to respond to cNAC is poor (5-y CSS = 27%). Therefore, up to half of MIUC could be amenable to alternative systemic therapies. Anti-programmed death ligand (PDL1) has shown promising results in tumors with proven PDL1 expression, including advanced stage MIUC. We evaluated PDL1 expression in MIUC in a cohort categorized by pathologic response to cNAC to test the hypothesis that anti-PDL1 therapy is a rational therapeutic option for patients non-responsive to cNAC. Methods: We studied 150 patients who received cNAC followed by open radical cystectomy (RC) from 2000-2013. Pathologic response (&lt;pT1 N0 at RC) and CSS were compared to patients who had RC without cNAC. Tissue microarrays of MIUC specimens representing patients with and without response to cNAC were stained with PD-L1 (Cell-Signaling, E1L3N, 1:100) and FOXP3 (eBioscience, 236A/E7, 1:250). The degree of tumoral PDL1 and tumoral lymphocyte FOXP3 staining was manually scored. Tumors with 5% and &gt;15/hpf staining were considered positive for PDL1 and FOXP3, respectively. Percentage of non-responders to cNAC staining positive for PDL1 was the primary outcome of our study. Results: The rate of PDL1 positivity in MIUC cNAC non-responders was 47% which was similar to the 43% rate in responders. There was a strong positive correlation of tumoral PDL1 staining with tumoral lymphocytes FOXP3 staining, Goodman-Kruskal gamma=0.71 (p&lt;0.0001), which was independent of cNAC responder status (Table). Conclusions: Patients with MIUC that are non-responders to cNAC have poor long term CSS. Our results demonstrate that cNAC non-responders exhibit frequent PDL1 tumoral staining, suggesting that neoadjuvant or adjuvant anti-PDL1 therapy represents an attractive therapy worthy of prospective clinical trial testing in MIUC patients whose tumors do not respond to or in patients who cannot tolerate cisplatin based chemotherapy. [Table: see text]
Predictors of pathologic complete response after neoadjuvant treatment for rectal cancer: A multicenter study.
Authors: Dawn Elizabeth Armstrong, Soundouss Raissouni, Julie A. Price Hiller, Jamison Mercer, Erin Diana Powell, Anthony MacLean, Maria Jiang, Corinne M Doll, Rachel Anne Goodwin, Eugene Batuyong, Kevin Zhou, Jose Gerard Monzon, Patricia Tang, Daniel Yick Chin Heng, Winson Y. Cheung, Michael M. Vickers
Journal: Journal of Clinical Oncology (2014)

397 Background: Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) for rectal cancer is associated with better long-term outcomes, and is used as an early indicator of response to novel agents. To assess the rate and predictors of pCR, we performed a retrospective population based study in four Canadian provinces. Methods: Cancer Registries identified consecutive patients with clinical stage I-III rectal cancer from the Tom Baker Cancer Center, Cross Cancer Institute, BC Cancer Agency, Ottawa Hospital Cancer Centre and the Dr. H. Bliss Murphy Cancer Centre who received fluoropyrimidine-based CRT and had curative intent surgery (Sx) from 2005 to 2012. Patient, tumor, and therapy characteristics were correlated with response. Results: Of the 891 patients included, 885 patients had pCR data available. 161 (18.2%) had a pCR to CRT, while 724 (81.8%) did not. Patients with a pCR had a lower pre-treatment (tx) CEA, and higher hemoglobin on univariate analysis (see table). On multivariable analysis, statin use at baseline (OR 1.7, 95% CI 1.04-2.89, p=0.044), lower pre-tx CEA (OR 1.03, 95% CI 1.003-1.05 p=0.028) and distance closer to anal verge (OR 1.07, 95% CI 1.004-1.15, p=0.039) were significant predictors of pCR. The 3yr DFS was 86% in those with pCR vs 62.5% in those without a pCR (P&lt;0.0001). Conclusions: Lower pre-tx CEA, distance closer to anal verge and statin use are predictors of pCR. Clinical trials investigating statins combined with neoadjuvant CRT may be warranted. [Table: see text]
Clinical outcomes of patients enrolled in clinical trial compared with patients outside clinical trial in advanced gastric cancer.
Authors: Jaejoon Han, Jin Won Kim, Se Hyun Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee
Journal: Journal of Clinical Oncology (2016)

21 Background: Participation in clinical trials gives patients with cancer a chance to receive potential benefits, such as experimental treatment, meticulous follow-up and toxicity managements. We aimed to assess the evidence that such an effect exists in patients with gastric cancer. Methods: Clinical characteristics and overall survival of patients with metastatic or recurrent gastric cancer who received fluoropyrimidine and platinum combination palliative chemotherapy within or outside clinical trials at tertiary referral hospital from January 2010 to December 2012 were retrospectively analyzed. Results: Of the 244 patients, 84 patients (34%) were enrolled in clinical trials. During the study period, 20 patients in four phase 3 trials, 54 patients in eight phase 2 trials and ten patients in two phase 1 trials were participated in clinical trials. Twenty patients (8%) at first-line and 64 patients (38%) at second-line or later were enrolled in clinical trials. Younger age (P = 0.014), metastatic disease (P = 0.015) and HER2 IHC status (P = 0.005) were correlated with participation in clinical trials. The median overall survival of patients who participated in clinical trials at first-line was better than those who did not participated in clinical trials, although it was not statistically significant (16 months and 11 months, respectively, P = 0.407). Number of participation in clinical trials was not associated with survival outcome (1 versus ≥ 2 trials: 15 months and 18 months, respectively, P = 0.545). Second-line chemotherapy was administered in 167 patients. The median overall survival of patients who participated in clinical trials at second-line or later was also better than those who did not participated in clinical trials, however, it was not statistically significant (9 months and 6 months, respectively, P = 0.101). Conclusions: Younger patients, metastatic disease, positive HER2 IHC status, and clinical setting of second-line or later were associated with more participation in clinical trials. The median overall survival was numerically longer in patients who were enrolled in the clinical trials although it was not statistically significant.
A case series of Lynch syndrome-associated breast cancer.
Authors: Kevin M. Zbuk, Mira Goldberg, Kathleen Bell, Kara Semotiuk, Steven Gallinger, Melyssa Aronson
Journal: Journal of Clinical Oncology (2014)

432 Background: Studies suggest breast cancer (BC) might be a feature of Lynch syndrome (LS). Further characterization of this risk is required before recommending increased surveillance for BC in LS families. This study describes the prevalence and characteristics of BC amongst LS families in a large familial cancer registry. Methods: The pedigrees of 325 families carrying an MMR gene mutation (149 MSH2 46%, 113 MLH1 35%, 38 MSH6 12%, 19 PMS2 5%, and 6 EPCAM 2%) within the Familial Gastrointestinal Cancer Registry (FGICR) were screened for a diagnosis of BC. The analysis was limited to known or obligate carriers of a MMR gene mutation. The diagnosis and age of diagnosis of BC was confirmed utilizing clinic records and pathology reports where available. Descriptive and Chi-squared statistics were utilized. Results: 39 female mutation carriers from 33 unrelated families with a diagnosis of BC were identified. The average age of BC diagnosis was 53y. The vast majority of families (25/33, 76%) carried MSH2 mutations. Of the 8 remaining families there were 6 (18%) MLH1 carriers, 1 (2.5%) MSH6 carrier, and 1 PMS2 carrier. The mutation distribution amongst the LS patients with BC was statistically different from those without BC (p = 0.008), reflecting the predominance of MSH2 mutations amongst patients with BC. Twenty-nine of 33 LS families with BC met Amsterdam Criteria (88%), compared with 142 of 292 LS families without BC in a known carrier (48%) (p = 0.03). LS associated BCs tended to be high grade (10 of 19 were grade 3), and 50% were ER/PR/Her2 negative. Additional manifestations in patients with BC included 9 women with colorectal cancer, 4 with multiple (2-4) colorectal cancers, 20 with endometrial cancer, 7 with cutaneous manifestations of LS, and 5 with genitourinary cancers. The mean number of additional LS related manifestations for these patients with BC was 1.5 (range 0-8) per patient. Conclusions: Within the registry utilized in this study, LS associated BC is strongly associated with MSH2 mutation status. Most patients with LS associated BC harbored multiple manifestations of LS, and their families almost always met Amsterdam criteria. LS associated BC was frequently high grade and often hormone receptor negative, suggesting an aggressive histology.
A retrospective study comparing demographics, cytogentic findings, and prognosis in acute myeloid leukemia with and without leukemia cutis
Authors: J. Shah, T. Latif, P. Elson, E. Hsi, M. Kalaycio
Journal: Journal of Clinical Oncology (2005)

6695 Background: Historically patients with skin infiltration by leukemic cells (Leukemia Cutis, LC) carried a poor prognosis. However, it is not clear if this is solely because of LC or other high-risk features commonly observed in these patients. Our objective was to determine if LC is independently associated with poor prognosis when controlled for other high-risk features. Methods: We identified AML patients with histologically confirmed LC and matched controls (matched for age, sex, year of diagnosis, and treatment) from 1990–2003 using Cleveland Clinic Department of Anatomic Pathology database and tumor registry. Medical charts were reviewed. Demographic, hematologic, and cytogenetic findings, and prognosis were compared. Results: Sixteen AML patients with histologically confirmed LC and 28 matched control patients were identified. Baseline characteristics and other high- risk features did not differ between the two groups (Table 1). No patient from either group had good-risk cytogenetics[t(8;21), inv (16), t(15;17)]. There was no statistically significant difference between the groups among complete remission rates after initial therapy (p=0.75). Median survival for LC patients was 5.0 months compared to 6.9 months for matched control patients (p=0.48, log rank test). Conclusions: Contrary to previous studies, no statistically significant difference in prognosis was found between the two groups. Older age and adverse cytogenetics at presentation and prior hematologic disorder may explain the poor overall median survival in this cohort. When controlled for other risk factors LC by itself does not correlate with worst prognosis in AML. No significant financial relationships to disclose.
Chemotherapeutic safety management system (CSMS) for the safe use of cancer chemotherapy (CTx).
Authors: K. Kawada, N. Hamajima, M. Amano, J. Ueda, K. Oji, M. Maeda, T. Kushihara, N. Mukoyama, H. Kushihara, Y. Ikeda, F. Nomura
Journal: Journal of Clinical Oncology (2011)

e19719 Background: How to administer cancer CTx safely is important. Occupational Safety and Health Management Systems (OSHMS) as proposed by the Ministry of Health, Labour and Welfare have spread to many companies in Japan. We therefore designed a CSMS based on OSHMS. Methods: We reached an agreement for the CSMS. Three main actions were taken: 1) we reduced risk through the positive use of risk assessment; 2) we continuously improved the system by using a plan-do-check-act cycle; and 3) we actively communicated with all staff members. We assessed risk according to a scale of 1 to 5 (with 5 indicating the highest risk) based on the degree and possibility of such risk. After scoring the risk, we estimated the degree of risk reduction, continuously assessed the results, and improved the system. Results: Between April 2009 and October 2010, a total of 4 risk assessments were performed. 1) Orders for the first course of CTx were checked by a medical oncologist, a pharmacist, and nurses (MOPN). The estimated risk (ER) was reduced from 3 to 2. 2) Orders for CTx in the outpatient clinic were checked by MOPN. The ER was reduced from 3 to 2. 3) The body weight of the patients was double-checked by two nurses. The ER was reduced from 3 to 2. 4) We set a time limit for checking orders for CTx by pharmacists. The ER was reduced from 3 to 2. An average of 69 first courses of CTx were given per month. Orders were modified in 13% of the patients as a result of checking, and the risk was reduced from 3 to 2. The average number of courses of CTx in the outpatient clinic was 364 per month. After checking, orders were modified in 6% of the patients. The risk was reduced from 3 to 2. There was one mistaken input of body weight after double-checking the weight of the patients. After that, we checked the patients’ history of body weight. There was no mistaken input of body weight after improving the checking system. The risk was reduced from 3 to 2. After setting a time limit for ordering CTx, the number of orders made after the designated time decreased. Pharmacists could check orders for CTx sufficiently. The risk was reduced from 3 to 2. Conclusions: The ER associated with cancer CTx was reduced by the CSMS. The CSMS promotes the safe use of cancer CTx and allows continuous improvements to be made.
<i>TP53</i> mutations in irinotecan-refractory <i>KRAS</i> wt-BRAF wt metastatic colorectal cancer patients treated with cetuximab-based chemotherapy.
Authors: F. Di Fiore, A. Lamy, F. Blanchard, A. Oden-Gangloff, R. Sesboüé, J. Sabourin, T. Frébourg, P. Michel, P. Laurent-Puig
Journal: Journal of Clinical Oncology (2011)

426 Background: Anti-EGFR antibodies are more efficient when EGFR pathway is activated without mutations on downstream effectors such as KRAS and BRAF (Lievre et al. Cancer Res. 2008 and Khambata-Ford et al. J Clin Oncol. 2007). Moreover, tumor growth from EGFR activation may required inactivation of the molecular brake p53 suggesting that anti-EGFR therapy should be more efficient if p53 is inactivated (Oden-Gangloff et al. Br J Cancer. 2008). The aim of the study was to evaluate, in an independent series, the impact of p53 mutations in irinotecan-refractory KRAS wt-BRAF wt MCRC patients treated with anti- EGFR. Methods: A total of 100 MCRC patients treated with cetuximab-based CT were included. KRAS and BRAF mutational status were determined using SNaPshot or allelic discrimination methods. TP53 mutations within exons 5 to 8 were detected using direct sequencing. Response to cetuximab, based on RECIST criteria, was evaluated according to molecular analysis using the Fischer exact test. Progression- free survivals (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared with log-rank test. Results: Objective response (OR = partial and complete response) was observed in 40% and control disease (CD = OR+stable disease) in 74% of patients. Median PFS and OS was 12 weeks and 12 months, respectively. TP53 mutations were detected in 66% of patients and were not significantly associated with OR and CD. In contrast, patients with KRAS wt-BRAF wt and TP53 mutation had significantly longer PFS as compared to KRAS wt–BRAF wt and TP53 non mutated patients (32 weeks vs. 21 weeks, respectively; p = 0.01). There was a trend but not significant increased OS in patients with TP53 mutations (16 months vs. 13 months) Conclusions: In this independent study, our results confirm that TP53 mutation was significantly associated with an increase PFS in irinotecan-refrcatory KRAS wt-BRAF wt MCRC patients treated with anti-EGFR. [Table: see text]
Proof of concept of immuno-PET molecular imaging of met using <sup>76</sup>Br- and <sup>89</sup>Zr-labeled MetMAb.
Authors: M. Merchant, J. Marik, J. Peng, S. P. Williams, A. Ogasawara, J. N. Tinianow, V. Bhadrasetty, L. Lang, S. M. Lee, I. Kim, M. Williams, L. Szajek, K. E. Raffensperger, F. Cecchi, E. Jagoda, P. L. Choyke, C. Paik, D. P. Bottaro
Journal: Journal of Clinical Oncology (2011)

10632 Background: Oncogenic signaling via the hepatocyte growth factor (HGF)/Met pathway promotes tumor cell proliferation, migration, invasion and survival. High levels of Met are poorly prognostic for multiple cancer subtypes, including non small-cell lung cancer (NSCLC) and pancreatic cancer. MetMAb is a monovalent monoclonal antibody that binds Met and blocks activation by HGF. Recent Phase II clinical studies show that the combination of MetMAb with erlotinib in 2nd-3rd line NSCLC significantly prolongs overall survival in patients whose archive tumor samples display high levels of Met. We investigated the feasibility of identifying diagnostically positive tumors in mouse xenografts by non-invasive immuno-PET imaging using either 76Br- or 89Zr -labeled MetMAb. Methods: MetMab was labeled directly with 76Br or conjugated with bifunctional chelator based on desferrioxamine B (Df-Bz-SCN) to form Df-MetMAb (1:1) for labeling with 89Zr. Met binding affinities of both forms of radiolabeled MetMab were determined using cultured cells. Biodistribution and imaging studies were done in mice bearing NCI-H441 (NSCLC), MKN-45 (gastric), U-87 MG (glioblastoma) or KP4 (pancreatic) xenografts at various time points. Plasma and tumor samples were taken to determine shed Met and tumor Met levels, respectively. Results: 76Br-MetMAb and 89Zr-Df-MetMAb retained nM binding affinity for human Met. Imaging and biodistribution studies showed rapid uptake and slow clearance of both tracers specifically in tumor xenografts. MKN-45 tumor uptake of 76Br-MetMAb correlated with tumor mass, Met abundance, and phosphoMet content. 76Br-MetMAb biodistribution was independent of plasma shed Met level, suggesting that plasma Met will not affect tumor imaging sensitivity. Tumor-to-muscle intensity ratio and signal stability values were also good for both tracers, and both robustly identified xenografts with high levels of Met, whereas 89Zr-Df-MetMAb was clearly superior for imaging the lower Met abundance U-87 MG xenografts. Conclusions: Radiolabeled MetMAb displays several promising features and warrants further development as an immuno-PET reagent to non-invasively image Met in vivo for diagnostic and prognostic endpoints.
Clinical outcomes of patients with tumor bed-to-skin distance (TBS) ≤ 7 mm treated with accelerated partial breast irradiation (APBI) using multilumen catheter.
Authors: Mirna Abboud, Paige Nitsch, Arnold Paulino, Angel Ignacio Blanco, Barbara Lee Bass, Kathleen M. Shadle, Bin S. Teh
Journal: Journal of Clinical Oncology (2012)

182 Background: The initial single-lumen Mammosite trial has shown that skin spacing had an important implication on cosmetic outcomes. In this study, we reviewed the patients who were treated with APBI using multilumen catheter and assessed the outcomes for patients with minimal TBS of ≤ 7mm. Methods: Between August 2008 and April 2011, 79 patients were treated with breast-conserving therapy and adjuvant APBI using the Contura Multi-Lumen balloon or strut-adjusted volume implant (SAVI) device. All patients received 3,400 cGy in 10 fractions delivered twice daily using high dose rate radiation with Iridium 192. The dose was prescribed to 1 cm from the applicator surface. Thirty-six patients had a TBS of ≤ 7mm. We analyzed the clinical outcomes according to RTOG 9517 and skin toxicities as per RTOG 9804 in this patient subgroup. Results: The median age was 65 years (range, 50-86 years). All patients had Tis-T1N0 carcinomas; 39% had DCIS and the rest had invasive carcinoma. The majority (92%) were treated with Contura Multi-Lumen balloon and 8% with SAVI. Median follow-up was 18 months (range 6-42 months). The average TBS was 4.8 mm (range 1-7). 21 patients (57%) had a TBS of ≤ 5mm. The median maximal skin dose was 116% (range 82-134%). The median V90, V95 and V100 were 98%, 96% and 92% respectively. The average V150 and V200 were 31.2 and 9.6 cc respectively. At a median of 3 weeks after treatment, 95% of the patients had good to excellent cosmetic outcome. 54% had grade 1, 21% patients had grade 2 skin toxicity and 25% did not have any skin reaction. At last follow-up, 82% of the patients did not have any residual late skin reaction. Grade 1 skin toxicity was reported in 13%, and grade 2 in 1 patient. Cosmesis was excellent in 72% and good in 28% of the patients. There was no loco-regional recurrence. Conclusions: In our patient population, APBI proved to be an effective treatment with a good to excellent cosmetic outcome and acceptable toxicity. Further investigation with larger patient populations and longer follow-up is warranted to confirm the safety and efficacy of APBI for patients with small TBS.
Necrobiotic Xanthogranuloma (NXG) Associated with Monoclonal Gammopathies (MG): Clinical Features and Treatment Outcomes
Authors: Larissa Higgins, Ronald S. Go, Shaji Kumar, S. Vincent Rajkumar, Francis Buadi, Martha Q. Lacy, Angela Dispenzieri, David Dingli, John A. Lust, Prashant Kapoor, Robert A. Kyle, Morie A. Gertz, Wilson I. Gonsalves
Journal: Blood (2015)
Association of colorectal cancer susceptibility variants with tumor subtypes in three large prospective cohorts.
Authors: Xabier Garcia-Albeniz, Hongmei Nan, Charles S. Fuchs, Edward L. Giovannucci, Jing Ma, Shuji Ogino, Peter Kraft, Andrew T. Chan
Journal: Journal of Clinical Oncology (2012)

445 Background: Genome-wide association studies (GWAS) have identified 17 colorectal cancer (CRC) susceptibility variants. However, their association with specific tumor subtypes has not been fully defined. Methods: We genotyped (TaqMan OpenArray) 17 variants (rs6691170, rs6687758, rs10936599, rs11169552, rs7136702, rs6983267, rs16892766, rs10795668, rs3802842, rs4444235, rs4779584, rs9929218, rs4939827, rs10411210, rs961253 , rs7014346 and rs2151512 as proxy of rs4925386) in three independent prospective, CRC case-control studies nested within the Nurses’ Health Study, Health Professionals Follow-up Study, and Physicians Health Study cohorts (1227 cases, 2201 age- and race-matched controls). Genotyping success: 98.1%. All variants fitted HWE (P&gt;0.05). We assessed the association of these variants with risk of CRC using logistic regression (LR) adjusted for age, race and study under an additive model. We used multinomial LR models to examine the association of variants to CRC according to T, N and M-stage, grade of differentiation, tumor site, and age at diagnosis. Heterogeneity in the associations were evaluated by a case-case only LR model. Results: We observed associations with CRC for rs6983267 (OR 0.86, 95% CI, 0.77-0.95; p=0.0028 -T allele-), rs3802842 (OR 1.18; 95% CI, 1.05-1.31; p=0.0036 -C allele-), rs7014346 (OR 1.15, 95% CI, 1.04-1.28, p=0.0082 -A allele-), rs11169552 (OR 0.88, 95% CI 0.78-0.99 -T allele-) and rs4939827 (OR 0.90, 95%CI 0.82-1.00, p=0.0508 – C allele-). The association between rs4939827 (MAF 48.34%) and risk of CRC was significantly different according to T stage (p for heterogeneity &lt; 0.0001). rs4939827 was associated with a lower risk of CRC with tumor stage T1 or T2 (OR, 0.72; 95% CI, 0.63-0.84, p&lt;.0001) but not of cancers with tumor stage T3 or T4 (OR, 1.04; 95% CI, 0.92-1.19). This result is consistent within each cohort. Conclusions: Among 17 CRC susceptibility variants, we observed that the minor allele of rs4939827 was associated with a lower risk of colorectal cancers with lower T stage but not higher T stage. These results suggest that rs4939827, which codes for an intronic region of SMAD7, may be mechanistically related to tumor invasiveness.