tbuckley/cabot-search huggingface dataset:
Incidence of brain metastases in HER2+ gastric or esogastric junction adenocarcinoma.
Authors: Christophe Blay, Danchristian Chiforeanu, Eveline Boucher, Florian Cabillic, Romain Desgrippes, Bérengère Leconte, Sylvain Manfredi, Bernard Meunier, Julien Edeline
Journal: Journal of Clinical Oncology (2013)

126 Background: HER2 overexpression is associated with a high risk for brain metastases in breast cancer. We aimed to study if the same correlation exists in gastric or oesogastric junction (OGJ) adenocarcinoma, where brain metastases are uncommon. Methods: We retrospectively reviewed data of patients treated at our institution for metastatic gastric or OGJ adenocarcinoma. We compared incidences with a Fisher’s exact test. Survival was analyzed by the Kaplan-Meier method. Results: Between 2007 and 2011, 74 patients were treated at our institution, 63 patients were analyzed for HER2 status. Median age was 62 (range: 22-81). There were 52 men (82.5%) and 11 women (17.5%). 36 patients (57.1%) had gastric cancer, 27 (42.9%) OGJ adenocarcinoma. After a median follow-up of 9.4 months, 52 patients progressed and 38 patients died. Median progression-free survival was 5.3 months and median overall survival was 15.9 months. 38 patients (60.3%) had hepatic metastases, 32 (50.8%) lymph node metastases, 20 (31.7%) peritoneal carcinomatosis, 12 (19.0%) lung metastases and 3 (4.8%) brain metastases. HER2 was overexpressed in 11 (17.5%) patients (confirmed by IHC in 58 patients, by FISH in 5 patients). Two HER2+ patients did not received trastuzumab. Three HER2+ patients (27.3%) had brain metastases, as compared with 0 (0%) HER2- patients (p=0.004). Control of brain metastases was obtained in all 3 patients with multimodal treatment (surgery for 1 patient, radiotherapy for 3 patients and trastuzumab-containing chemotherapy in 3 patients). Progression-Free Survival (PFS) was significantly higher in HER2+ patients treated with trastuzumab than in HER2- patients: median 9.4 months vs 5.0 months (p=0.049). There was no apparent difference in PFS or overall survival between patients with or without brain metastases, but the numbers are too small to conclude. Conclusions: In this retrospective single-center series, we showed an increased incidence of brain metastases in patients with HER2+ gastric or OGJ adenocarcinoma. Patients with brain metastases benefited from multimodal treatment. Prognosis of HER2+ patients treated with trastuzumab seems better than HER2- patients. These results need confirmation in a multicenter study.
Factors influencing a patient’s decision to provide a biopsy: Survey of 362 patients in a phase I oncology clinic.
Authors: E. C. Iwuanyanwu, R. Kurzrock, S. A. Piha-Paul, J. J. Wheler, G. S. Falchook, R. Mistry, B. Tavana, X. Lei, D. S. Hong
Journal: Journal of Clinical Oncology (2011)

e13032 Background: Phase 1 trials are initial steps in the development of novel anti-neoplastic drugs. Traditionally, the purpose has been to assess safety but increasingly the shift to targeted therapy has led to co-development of surrogate markers. Obtaining tumor tissue from patients (pts) is critical but there is limited research on pts’ factors/characteristics leading to participate in trial biopsies. To identify these factors, we conducted a survey of 362 pts referred to the phase 1 clinic at MD Anderson Cancer Center (MDACC) Methods: An anonymous self-administered survey was conducted in 362 pts. Survey included questions about socioeconomic characteristics, diagnosis, perceptions about their prognosis, understanding of the trial, quality of life (QOL), previous biopsy experience, biopsy experience in a current trial, and willingness for future biopsies including required, multiple, and optional biopsy. Associations between demographic and clinic characteristics of pts surveyed and willingness to provide biopsy were explored. Data were analyzed using summary statistics, chi-square, and ordinal logistic regression (SAS 9.1). All tests were two-sided (p value of 0.05 or < -statistically significant). Results: Of 362 pts surveyed demographics included: < 60yrs (55%), caucasian (81%), Income>$60,000 (46%), good/excellent QOL (38%), >college education (74%), pts with previous biopsies (84%), pts who had no complications from their previous biopsies (74%). Multivariate analysis showed pts who had undergone a previous or recent biopsy were more willing to enroll in a trial requiring biopsies (p=0.03). Characteristics of those willing to enroll in a study requiring more than one biopsy were white (p=0.02), male (p=0.004), higher income (p=0.015), and better QOL (p=0.009). Those willing to undergo optional biopsies were also male (p=0.002) and had a recent biopsy (p=0.0013). Conclusions: Pts with previous or recent biopsies were more willing to enroll in trials with required, multiple, or optional biopsies. Sex, race, income and QOL also correlated with willingness for multiple biopsies.
Expression of Aldo-keto-reductase 1B1 (AKR1B1) in tubulocytic carcinoma of kidney.
Authors: Yasuhiro Hashimoto, Toshikazu Tanaka, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2016)

507 Background: Tubulocystic carcinoma of the kidney (TubCC) is a new entity of tumor not listed in the 2004 WHO classification. The tumor comprised tubules forming duct-like structures exhibiting hobnail change, and resembled collecting duct carcinoma (CDC) by immunostaining; thus, this tumor was named low grade CDC. Since then, similar tumors have been reportedly called tubulocystic carcinoma (TubCC)We explored the possibility whether Aldo-keto-reductase-1B1 (AKR1B1), osmoregulatory protein and abundant in collecting duct, can be used as a marker for the pathologic diagnosis of TubCC. Methods: We prepared anti-AKR1B1 monoclonal antibodies, examined expression of AKR1B1 protein in the human normal kidney. Immunohistochemical expressions of AKR1B1 was examined on normal kidney, 4 cases of TubCC, 10 cases of papillary renal cell carcinoma (pRCC), and 10 cases of invasive urothelial carcinoma (iUC). Results: AKR1B1 expression distributed preferentially in the renal medulla and not in the cortex, reflected by its high concentration in medulla (2.12 ±1.35 μg/mg) compared with cortex (0.13 ± 0.03 μg/mg). Immunohistochemically, AKR1B1 was strongly positive in 3 of 4 TubCC cases. AKR1B1 was negative in cases of either iUC or pRCC. Conclusions: Although the present study was small and preliminary, AKR1B1 may be a more specific and potentially useful marker for TubCC. [Table: see text]
Concomitant chemoradiation using weekly cisplatin for advanced squamous cell carcinoma of head and neck: Experience from a tertiary cancer center in India.
Authors: A. Sharma, B. K. Mohanti, A. Thakar, S. P. Chaudhary, S. Bhasker, S. Bahadur, A. Sharma
Journal: Journal of Clinical Oncology (2011)

5548 Background: CTRT is preferred non-surgical treatment for advanced SCCHN. Weekly or 3 weekly cisplatin (DDP) as a single agent is commonly used. Methods: Between 2001-2009, 713 pts of SCCHN (mostly stage III or IV) pts with PS<2 were treated with CTRT using - DDP 40 mg/m2 weekly for 6-7 weeks concomitantly with standard schedule of RT (70Gy/35# over 7 weeks) at AIIMS, New Delhi. Analysis of 691 pts whose records have been traced is reported here. We also tried to identify prognostic factors for survival. Results: Number of pts 713 (evaluated 691), Males- 640, Median age 51 (range 12-77; 160 were> 60 yrs). Primary site of disease: nasopharynx 105, oropharynx 358, hypopharynx 96, larynx 127, and others 24. 247 had stage III, 262 had stage IVA, and 45 had stage IVB disease. Baseline serum albumin was < 3.5gm/dl in 55 patients and >3.5 gm/dl in 568 pts. 497 pts completed > 5 weeks of DDP, and 566 received > 60 Gys of RT. Responses: CR in 435 (62%), PR in 112 (15.8%). Toxicity- 274 (39%) pts had grade III/IV (mucositis-215, myelosuppression- 24, vomiting-35). 8 died of toxicity. 152 required hospitalization (for various reasons) and 187 had treatment interrupted for variable period. Survival- Five years OS of whole group is 62% (median NR). Mean OS as per primary site is; nasopharyngeal 72 months, oropharyngeal 74 months, hypophayngeal 36 months (median), and laryngeal 83 months. OS for non-hypopharyngeal primary was superior to hypopharyngeal primary (p=0.008). Patients with low albumin had poor OS (median 19 months) vs NR in patients with > normal albumin (p=0<00001). Patients with stage <III had superior OS compared to stage IV (77 vs 73 months; p=0.02). In univariate analysis low albumin, hypopharyngeal primary, and stage IV disease were identified as poor prognostic factors. In multivariate analysis low albumin emerged as poor prognostic factor (HR=3.06; p=<0.0001). Conclusions: Weekly DDP is effective with manageable toxicity in advanced SCCHN (except hypopharynx). In multivariate analysis low albumin emerged as poor prognostic factor. This is one of the largest series from India reporting experience with weekly DDP in SCCHN.
Satisfaction evaluation of medical attention at breast cancer service at National Cancer Institute Mexico.
Authors: Rebeca Ramirez-Morales, Julieta Santamaria-Galicia, Lucy Aldama, Alejandra Bautista-Leon, Cristina Aguilar, Alberto Alvarado Miranda, German Calderillo Ruiz, Haydee Claudia Arce Salinas
Journal: Journal of Clinical Oncology (2013)

156 Background: Breast cancer is the leading cause of attention at the INCan. In 2012, 44,761 medical consults were given therefore 19,584 (44%) of those by breast cancer oncologists. The increasing percentage of patients could be associated with a quality attention deficit, crowded waiting room and a shorter time for consultations affecting patient communication and education. The goal of this study was to evaluate the quality attention given by breast cancer service with the purpose to design different strategies in order to improve quality and cordiality with our patients. Methods: Self-response surveys had been applied to patients with breast cancer at INCan. The variables investigated were demographic characteristics including age, education level, marital status and date of diagnosis. Also variables related with the quality of our medical and paramedical attention, global care support and the waiting time before consultations were asked. Results: 259 patients were interviewed, the median age was 50 years old (17-88), only 18% of them achieved university degree and 28.7% had less than elementary education. One third of our population lived in Mexico City; the rest of them came from different states from the center and south of the country. The waiting time in average was 2 hours (10 min -7 hours). Regarding to attention quality, 28% considered that waiting time should be shorter, 22% answered that doctor-patient relationship needs to improve. In this aspect, the main aspects to improve are: give information in detail including the patient and their relatives; a better explanation about their disease and treatment and also information about diet and physical activity, among others is needed. Finally, 9.3% suggested improvement in nursery service. Conclusions: The results showed that our effort is satisfactory. However our main goal is to improve our medical assistance. It has been proven that patient education and higher satisfaction level improves their adherence and the knowledge related to handle adverse effects of their treatment. Our proposals include psycological-educative strategies easy to understand. Enhance medical services to improve physician-patient relationship. We will keep looking forward about the efficiency of these strategies.
Generating a neoantigen map of advanced urothelial carcinoma by whole exome sequencing.
Authors: Bishoy Faltas, Bhavneet Bhinder, Himisha Beltran, Scott T. Tagawa, Ana M. Molina, David M. Nanus, Olivier Elemento, Mark A. Rubin
Journal: Journal of Clinical Oncology (2016)

354 Background: immune-checkpoint blockade is a promising treatment of advanced urothelial carcinoma (UC) that unleashes pre-existing immune responses against recognized tumor antigens. Somatic mutations lead to the formation of neoantigens, which are highly antigenic mutant proteins. Methods: Our objective was to generate a neoantigen map through analysis of whole exome sequencing data of our cohort of patients (pts) with platinum-resistant UC. Whole exome sequencing (WES) data from 73 prospectively collected UC samples from 34 patients were analyzed using our neoantigen prediction pipeline. We defined neoantigens as mutant nonamers with high affinity binding to predicted class I MHC molecules for each patient. HLA haplotypes were inferred from WES of matched germline DNA. Results: A significant correlation between global somatic mutation rates, and neo-epitope burden was observed (R 2 = 0.93), a similar correlation was observed between single nucleotide variants (SNV) and neo-epitope burdens (R 2 = 0.94). We identified a strong positive correlation between the numbers of pack-years of smoking and neoepitope burden in patients with advanced UC (p = 0.0004). No correlation between global somatic mutational and predicted neoepitope burdens with overall survival was identified. Metastatic samples had a trend of harboring more SNVs (median 49 vs. 22, P = 0.13), and neoepitopes (median 17 vs 12, P = 0.22) compared to primary samples. Interestingly, only 32% of total SNVs and 8 % of neoepitopes (with binding affinities of ≤ 50nM) that were initially identified, reappeared in metastatic samples from the same patients obtained at a later time point. A significant selection against strong binding neo-epitopes was observed in subsequent samples from metastatic tumors (p-value &lt; 0.005). Conclusions: A strong correlation between mutational burden and predicted neoantigenic load was observed in UC. Neoantigenic signatures were shaped by environmental exposures such as smoking. The significant heterogeneity in primary and metastatic neoantigens was possibly due to immunoediting as the tumor evolved. These findings may have important implications for selecting patients for immunotherapeutic approaches.
Detection of circulating breast cancer cells in relation to therapy
Authors: O. Bitisik, P. Saip, S. Saglam, N. Dalay
Journal: Journal of Clinical Oncology (2005)

689 Background: The identification of circulating tumor cells in the peripheral blood of breast cancer patient could potentially become an important prognostic factor for survival, because early occult dissemination of tumor cells is one of the major causes of relapse after local threatment. Various molecular markers have been proposed to detection circulating breast cancer cells, we compared the specifity and the sensitivity of human mammoglobin (hMAM) and maspin expression as a marker. Methods: Blood samples from 85 patients (mean age, 50.26±10.07) with invasive breast carcinoma, before and after chemotherapy and 20 healty volunteers were screened for mRNA encoding hMAM and Maspin by nested RT-PCR. Results: Prior to therapy, 10 patients (11.8%) were positive for hMAM. (proportion:%13,16 and %95 CI: 6.49–22.87), 20 patients (23.5%) were positive for Maspin mRNA. (Proportion.:%25.64, %95 CI:16.42–36.79) Following threatment, only one patient remained positive for hMAM (Proportion:%1.32, %95 CI:0.3–7.11)and 3 patients remained positive for Maspin mRNAs. (Proportion: %3.85, %95 CI: 0.8–10.83) This probably reflects the effects of systemic therapy on circulating tumor cells. On the other hand, Mammoglobin transcript were positive in 8 patients and maspin transcript were positive in 7 patients following threatment. This may be associated with disease progression. No difference in the rate of positivity was observed between groups defined accordind to age or stage. All of healty control were negative for hMAM and Maspin mRNAs. The median follow-up interval after blood sampling was 14 months (range 2–27 months; mean 13.53±6.56 months) for the patients. Conclusions: The specifity of Mammoglobin and Maspin for circulating tumor cells were high (100%); however the sensitivity of hMAM was considerably lower (11.8%) when compared to Maspin (23.5%). We suggest that this molecular assay can identify circulating tumor cells and may asist in monitoring the eficacy of treatment. However, serial analysis of large number of samples is needed. No significant financial relationships to disclose.
The optimum number of retrieved lymph nodes for locally advanced rectal cancer following short-course preoperative radiotherapy: A study by fat clearance.
Authors: J. Gu, L. Wang
Journal: Journal of Clinical Oncology (2011)

449 Background: The optimum number of retrieved lymph nodes following preoperative radiotherapy and surgery for locally advanced rectal cancer is still controversial. This study is designed to confirm the least number of retrieved lymph nodes for locally advanced rectal cancer following 30Gy/10f short-course preoperative radiotherapy. Methods: From Aug 2002 to Mar 2010, two hundred and twelve patients with locally advanced rectal cancer received 30Gy/10f preoperative radiotherapy (BED: 36Gy), standardized total mesorectal excision and fat-clearance based pathological evaluation in Beijing Cancer Hospital. The size of retrieved lymph nodes (LNs) was recorded. The sequence of LNs was arranged by a descending sort by retrieved nodes' size and the serial number of the largest metastatic lymph node (mLN) was recorded. The serial number of the first largest mLN is regarded as the least number of LNs to distinguish ypN+ status. The cumulative accuracy of ypN stage by variable numbers of LNs was calculated and analyzed. Results: There were total 4,669 retrieved LNs and 354 mLNs. The median retrieved LNs number was 21 (range 4-61). The ypN positive rate was 40.6%. The peak-value of quantitive distribution of LNs and mLNs was observed in 1-2mm and 3-4mm level. The incidence of retrieving mLNs shows an intensifying tendency for increasing size of LNs. The analysis for sequence of LNs sorting suggested that 85.4% of cases could confirm their ypN stage by the first largest LN. The cumulative accuracy ascended to 95.1% or 98.1% when the first 5 or 9 largest LNs were retrieved. Conclusions: For rectal cancer following 30Gy/10f preoperative radiotherapy, retrieving 12 or more lymph nodes seems not to be mandatory for confirming ypN stage. The accuracy in confirming negative ypN stage when retrieving 5 or 9 largest nodes is sufficient for majority of patients. In those cases that could not retrieve 5 or more nodes by routine fixation, fat clearance is indispensable. No significant financial relationships to disclose.
Clinical outcomes and prognostic factors of adjuvant treatment in resectable biliary tract cancer.
Authors: Ji Hyung Hong
Journal: Journal of Clinical Oncology (2014)

370 Background: The survival outcomes and prognostic factors of adjuvant treatment after resection for biliary tract cancer (BTC) has not been clearly established. We analyzed the clinical outcomes and prognostic factors of patients with resected BTCs between adjuvant treatment and non-adjuvant treatment group. Methods: A total 189 patients of BTC were treated with surgery followed by adjuvant chemotherapy or concurrent chemoradiotherapy between Jan. 2008 and Jan. 2013. We retrospectively analyzed the clinical characteristics and recurrence and survival outcomes with following variables: histologic grade, resected margin status, lymphatic/vascular/perineural invasion, T and N stage, treatment modality. Results: Median age at diagnosis was 64 years (range: 32-85). Of the total 189 patients, R0 resection was done in 152 patients (80.4%). Among the 73 patients with adjuvant treatment, forty-one patients (21.6%) were treated with adjuvant 5-FU based systemic chemotherapy and 31 patients with chemoradiotherapy (16.5%). Recurrence rate were 39.7%. Median disease free survival (DFS) time was 58.1 months (95% CI, 38.9-77.3) and median overall survival (OS) time was 87.8 months (95% CI, 79.5-96.0). Adjuvant treatment showed the tendency to improve DFS with 39.0 months (95% CI, 8.9-69.1) in the adjuvant group compared with 57.0 months (95% CI, 39.5-74.5) in the non-adjuvant group, however, without statistical significance (p=0.113). Between the recurrent and non-recurrent group, perineural invasion, lymphatic invasion and poorly differentiated histology showed statistical significant difference, respectively (65.3% vs 35% ; p &lt;.001, 28% vs 14.9% ; p = .028, and 8.1% vs 7.1% ; p = .011). Presence of perineural invasion showed association with RFS (HR= 1.543; 95% CI 1.133-2.102, p=.006). There was no other significant correlation in R1 resection, poor histologic grade, lymphatic and vascular invasion, chemotherapy regimen, and treatment modality with survival outcome. Conclusions: Perineural invasion could be a potential prognostic factor for recurrence. Further prospective study should be warranted to confirm this data.
Impact of early tumor shrinkage on long-term outcome in metastatic colorectal cancer (mCRC) treated with 5FU plus irinotecan plus leucovorin (FOLFIRI) or capecitabine plus irinotecan XELIRI plus bevacizumab.
Authors: J. Ichante, A. Adenis, D. Malka, E. Francois, E. Boucher, B. Chauffert, J. Pignon, M. Ychou, J. Pierga, C. Montoto-Grillot, T. Conroy, M. Ducreux
Journal: Journal of Clinical Oncology (2011)

e14041 Background: The measurement of ETS at 8 weeks was reported to predict long-term outcome in first line mCRC treated with irinotecan based chemotherapy (CT) + cetuximab. This study has for aim to evaluate the impact of ETS on long-term outcome in patients (pts) receiving irinotecan based CT + bev. Methods: The pts treated in the randomized phase II trial ACCORD 13 (FOLFIRI + bev vs. XELIRI + bev) previously reported (Ducreux, ASCO 2009, abs 4086) were included in this post-hoc analysis with a 36 months follow-up. Based on the 8-weekly radiological assessments reported by the investigators, relative changes of the tumor size from baseline were dichotomized using a 20% decrease cut-off value. Univariable analyses for progression-free survival (PFS), and overall survival (OS) were based on logrank test. Multivariable analysis used Cox model and included ETS, Köhne prognostic score; age, sex, and treatment arm. Results: 2 pts out of 145 were excluded from this analysis because of early death. One patient had GI perforation at week 6 and was considered as non responder. ETS was observed in 87 pts out of 143 (61%). All the RECIST responders (46) had early shrinkage. Median PFS was 10 months and 9 months in pts with and without ETS. PFS rates were 97% and 75% at 6 months, 23% and 20 % at 12 months in the pts with and without ETS, (HR = 0.84; [0.59 – 1.20], p=0.35). Median OS were 33 months and 22 months for pts with or without ETS. OS rates were 93% and 79 % at 12 months in the pts with or without ETS, the corresponding rates at 24 months were 52% and 36 % (HR = 0.59; [0.36-0.97], p=0.04). The multivariable analysis showed that ETS had the strongest independent prognostic value when added to the OS model (HR = 0.54 [0.32-0.92] p=0.02), age: p=0.07, other variables: p>0.28. Conclusions: Combination of fluoropyrimidines + bev gives rapid responses. ETS is able to determine patients with prolonged survival rarely observed in mCRC. Despite the absence of effect of ETS on PFS, these results are similar or even better to those observed with CT + cetuximab. Their relevance in terms of daily clinical practice remains debatable and need to be confirmed.