tbuckley/cabot-search huggingface dataset:
Long-term oncological and functional outcomes of prostate sparing cystectomy: Single tertiary care institution experience.
Authors: Jose Ignacio Perez-Reggeti, Rafael Sanchez-Salas, Estefania Linares Espinos, Alexandre Ingels, Arjun Sivaraman, Mohamed Saad, Francois Rozet, Eric Barret, Marc Galiano, Nathalia Cathala, Annick Mombet, Dominique Prapotnich, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2016)

413 Background: To analyze the oncological and functional outcome of Prostate Sparing Cystectomy (PSC) in the treatment of Bladder Cancer (BC) in a single tertiary care referral institution. Methods: At our institution, we treated 147 patients (1992 – 2014) with PSC for muscle invasive BC and recurrent high grade non-muscle invasive BC. Out of these, 64 patients received a standardized PSC technique featuring a Millin adenomectomy between 2001 – 2014 and composed the population of the study. Inclusion criteria were: Normal prostate examination and prostate specific antigen (PSA) +/- negative transrectal ultrasound guided biopsies; Frozen section negative for cancer in prostatic urethra prostate base, distal ureters and trigone. Oncological outcome was evaluated with Overall survival (OS); Cancer-specific survival (CSS); Recurrence-free survival (RFS). Functional outcomes: Continence - being pad-free or leak-free requiring ≤ 1 pad per day/night. Sexual function was assessed by self- reported erectile function sufficient for intercourse with or without medical treatment. Results: Median age was 62 years (IQR 55-67,5) with a median follow-up of 70 months (IQR 46-103). Thirty one (48,4%) patients ≤ pT1, 19 (29,7%) pT2, 14 (21,9%) ≥ pT3 at pathological diagnosis. Lymphadenectomy was performed in 95,3% of the cases. Positive lymph nodes were found in 4.9% patients and 3.1% patients showed positive surgical margins. Ten patients (15,7%) had Clavien grade 3–5 complications.The 5 and 10-y survival rates were OS: 84,7% and 68,3%; CSS: 84,7% and 77,5%; RFS: 76% and 65,5% respectively. No case of recurrence at the remnant prostatic urothelium was observed. Pad-free and leak-free continence, were achieved in 85.9% and 93.8% for daytime continence respectively, with 50% and 85,9% for night continence, respectively. Erectile function was maintained in 56,3%. Prostate cancer was diagnosed in 3 (4,7%) patients, 2 at the pathology report of the adenomectomy followed with active surveillance, and 1 was diagnosed during the follow up being treated with brachytherapy. Conclusions: PSC appears to be an oncologically safe procedure with adequate functional outcomes in treating selected patients with BC.
Association of death receptor 4 variant (Glu228Ala) with ovarian cancer risk in BRCA1-mutation carriers.
Authors: M. G. Dick, B. Versmold, C. Engel, C. Sutter, R. K. Schmutzler
Journal: Journal of Clinical Oncology (2010)

1537 Background: Dysregulation of apoptosis plays an important role in carcinogenesis. Therefore, apoptosis-associated genes like the death receptor 4 (DR4, TRAIL-R1) are interesting candidates for the modification of disease penetrance in BRCA1 and BRCA2 mutation carriers. Recently it was shown that the DR-4 Haplotyp 626C-683C (626 C > G, Thr209Arg (rs4871857) and 683 A > C, Glu228Ala (rs17088993)) is associated with an increased risk of breast cancer (Frank et al. 2005). Methods: In order to evaluate whether DR4 626 C > G or DR4 683 A > C modifies the risk of breast or ovarian cancer in BRCA1 and BRCA2 mutation carriers, we undertook a multi-centre study including data of 839 (T209R) / 840 (E228A) BRCA mutation carriers. The DNA-samples, which were collected in 12 German research centers during the years 1996-2005, were genotyped by Taqman allelic discrimination assay. Results: We found evidence for a significant association with DR4 683 A > C of ovarian cancer risk in BRCA1/2-mutation (p = 0.010) and BRCA1-mutation (p = 0.002) carriers, whereas neither association was found for DR4 626 C > G nor with the 626C- 683C-haplotype. Conclusions: In summary, our results indicate that the DR4 683A > C variant modifies the risk of ovarian cancer in BRCA1 mutation carriers. This could be due to the fact that both SNPs reside next to the DR4 ligand-binding ectodomain and may affect TRAIL binding and therefore apoptotic signalling. No significant financial relationships to disclose.
Cetuximab in first-line treatment of metastatic colorectal cancer in a real-life setting: Preliminary results of the EREBUS cohort.
Authors: Denis Smith, Magali Rouyer, Emmanuel Mitry, Alain Monnereau, Antonio Sa Cunha, Emmanuelle Bignon, Alise Le Monies, Jeremy Jove, P. Noize, Nicholas Moore, Annie Fourrier-Réglat
Journal: Journal of Clinical Oncology (2012)

621 Background: Cetuximab (CTX) has demonstrated to improve survival outcomes in metastatic colorectal cancer (mCRC), but little data for real-life use is available. Methods: EREBUS is a French multicentre (n=92) hospital-based cohort. Patients initiating CTX in 2009 and 2010 were identified retrospectively from registries of nominative drug dispensations. Those with wild-type KRAS gene receiving 1 st -line treatment for mCRC were followed-up for 12 months. Data were collected from patient medical records and response based on physician assessments (CT-Scan). Presented here are preliminary results of the EREBUS cohort about administration regimen and according response rates for patients included in 2009. Results: Of the 190 patients included in the cohort, data has been collected for 160 (84.2%): median age at baseline 65.5 years, 70.6% male. Regarding cancer characteristics, 79.4% of patients had a colon cancer and 53.8% a primary tumor resection. Metastatic sites were liver in 73.1% of patients, peritoneum in 29.4%, lymph nodes in 26.3%, and lung in 25.6%. For patients for which the ECOG status was available (54.4%): 79.3% have an ECOG score between 0 and 1, 20.7% ≥2. Half the patients (48.8%) had only one metastatic site. CTX was given every three weeks to 2 patients (1.3%), every two weeks to 113 of patients (70.6%), and weekly to 45 (28.1%). For those receiving CTX every two weeks: 64.9% had irinotecan-based regimens (vs. 45.5% of those receiving CTX weekly, p=0.03), 31.5% had oxaliplatin-based regimens (vs. 47.7%, p=0.06), median duration of CTX use was 3.8 months (vs. 5.3 months, p=0.69) and that of 1 st -line therapy 6.3 months (vs. 7.5 months, p=0.97), 69.0% discontinued 1 st -line treatment (vs. 82.2%, p=0.09) – mainly for progression (71.8 vs. 75.7%, p=0.66) or toxicity (20.5 vs. 10.8%, p=0.20). Overall response evaluated for 100 patients receiving CTX every two weeks out of 113 was 46.0% (vs. 52.6%, p=0.49, evaluated for 38 receiving CTX weekly). Conclusions: CTX administration every two weeks was the most frequent regimen. In this preliminary analysis, patients receiving weekly or every two weeks regimens had similar duration of treatment and response rate.
Molecular evidence demonstrating that local treatment failure is the source of distant metastases in some patients treated for breast cancer
Authors: F. Vicini, N. S. Goldstein, M. Wallace, L. Kestin, S. Schell
Journal: Journal of Clinical Oncology (2008)

1098 Background: Clonality relationships between initial invasive breast carcinomas (IBCs), ipsilateral breast failures (IBFs), and distant metastases (DMs) were examined. Methods: Eighteen patients treated with breast conserving therapy who developed an IBF followed by DMs were studied using a 20 informative-marker, PCR-based allelic imbalance clonality assay. Results: Four relationships were identified: (1) In 7 cases, the IBF and DMs were clonally related to the initial IBC as one, progressively genetic unstable process; (2) in 3, the IBF and DMs were each clonally related to the IBC but clonally distinct to each other; (3) in 3, the IBC and the IBF were clonally related and DMs were clonally related to the IBFs with a weak relationship with the initial IBC; and (4) in 5, the IBF was clonally distinct from the initial IBC (new second primary) and the DM was clonally related to the IBF and clonally distinct from the initial IBC. Conclusions: IBFs can be the primary source of DMs. Not all IBFs that produce DMs are clonally related to the initial IBC, some are new second carcinomas. Some initial IBCs have multiple subclones which appear to have different and unrelated IBF and DM potential. No significant financial relationships to disclose.
Waiting room related symptoms: Patients’ experiences in an outpatient clinic of a cancer center
Authors: C. Catania, D. Micheli, I. Minchella, T. M. De Pas, L. Adamoli, M. Medici, E. Munzone, F. Nolè
Journal: Journal of Clinical Oncology (2008)

20614 Background: Duration of staying in the waiting room might increase discomfort in patients with sever disease like cancer. For care givers, increased waiting period is perceived as stealing time from someone who would be happy to use it otherwise. Furthermore, increased waiting time might also mean forcing patients into a potentially undesired contact with others. The goal of this study was to identify, for patients with cancer, features of mood and fears in a waiting room and to capture their concrete proposals for an “anthropocentric” transformation of the waiting itself. Methods: A 15-item questionnaire comprehensive of a trade-off question, developed through patient interviews and satisfaction questionnaires, was administered to 355 patients who came to the outpatient oncological hospital for visits and treatment. Results: Patients felt that period of waiting is at low (55%), high or very high (28%) emotional cost for them and found waiting to be boring (48%) or distressing (16%). The greater emotional impact while waiting was seeing other sick people and their clinical decline (26%).More than half the patients find discussing their condition with other patients comforting; 62% are not upset to talk about their condition with others while waiting and 89% expressed desire for alternative activities to be organized during the waiting period such as structured meetings with specialists (31%), psychologists (24%), organized music (23%) and drawing courses (10%); fifty-five percent of patients believed the hospital should offer alternative activities to make them feel as normal human beings, rather than as “only” sick people. Conclusions: This study offers sufficient information on problems related to waiting at a cancer treatment ward, confirming the complexity and heterogeneity of its perception by patients. It also leads to recognize some unexpected positive aspects, like that a “collective” rather than “individual” waiting is not considered negatively. An “anthropocentric transformation” of the waiting is strongly evocated by most patients with cancer. No significant financial relationships to disclose.
Role of KRAS mutations in the carcinogenesis of mucinous tumors of appendiceal origin with pseudomyxoma peritonei (PMP).
Authors: Filippo G. De Braud, Filippo Pietrantonio, Federica Perrone, Marcello Deraco, Dario Baratti, Shigeki Kusamura, Massimo Milione, Elena Tamborini, Katia F Dotti, Maria Di Bartolomeo, Claudia Bertan, Giuseppe Fanetti
Journal: Journal of Clinical Oncology (2013)

202 Background: Codon 12 KRAS and BRAF mutations may have a role in the mucinous differentiation pathway in colorectal cancer (Bazan V et al, Ann Oncol 2002; Tran et al, Cancer 2011). Elucidating the molecular mechanisms driving this disease is a priority for PMP, with the goal of identifying new markers and therapeutic targets needed to improve disease management. Due to the fact that neoplastic cells may be deceptively bland and sparse histologically within an abundant mucinous background, the adoption of high-sensitivity gene sequencing techniques may be extremely helpful. Methods: Mucinous tumors from 10 PMP cases of appendiceal origin treated in a multidisciplinary team at the National Cancer Institute of Milan were histologically classified according to Bradley classification. Following microdissection and DNA extraction, mutational analysis of KRAS exon 2-4 and BRAF exon 15 were performed by means of PCR, while KRAS exon 2 status was further confirmed through a specific mutant enriched PCR, shown to be a more sensitive approach in colorectal cancer (Molinari et al, Clin Cancer Res 2011). Results: Histological classification was low-grade in 6 and high-grade in 4 tumors. Codon 12 KRAS mutations were detected in 5/10 cases (50%). In the remaining 5 cases: sequencing of exon 4 lead to identification of a first-described A146V mutation in 1 case; with mutant enriched technique, we identified 3 additional codon 12 mutated cases. Due to use of high sensibility techniques and gene sequencing outside hotspot regions, we were able to identify KRAS mutations in 9/10 (90%) specimens. No BRAF exon 15 mutation was detected. Conclusions: The prognostic role of KRAS mutation in PMP patients is under investigation on a larger data-set of National Cancer Institute of Milan and will be presented at the Meeting. However, these preliminary data suggest a major role of KRAS in the carcinogenesis of mucinous tumors of appendiceal origin with PMP.
Smoking and binge drinking among cancer survivors: The forth Korean national health and nutrition examination surveys (KNHANES IV, 2007-2009).
Authors: Mi Ah Han, Myeung Guen Oh, Jong Park, So Yeon Ryu, Seong Woo Choi
Journal: Journal of Clinical Oncology (2012)

28 Background: This study aimed to describe the prevalence of smoking and binge drinking among cancer survivors in Korea, and to compare these rates with those of two control groups: individuals without a history of cancer but with other chronic diseases, and individuals without a history of cancer and without other chronic diseases. Methods: The study is a cross-sectional analysis of 37,878 adults ≥20 years old who participated in the Forth Korean National Health and Nutrition Examination Surveys (KNHANES IV, 2007-2009). The prevalence of smoking and binge drinking were assessed and compared to two control groups. Logistic regression analyses were performed to determine the likelihood and predictors of current smoking and binge drinking. Results: The prevalence of smoking and binge drinking were 9.6% and 6.6% among cancer survivors, respectively. Cancer survivors showed lower smoking rate compared with both control groups after adjusting gender, age, marital status, education, income and health insurance. Survivors’ smoking and binge drinking did not vary substantially by the clinical factors assessed. Conclusions: In our study, the smoking rate was significantly low in cancer survivor compared with both control groups. This result suggested that cancer survivors were more likely than individuals without a cancer history to obtain good health related behavior.
The impact of persistent dysphagia (PD) after induction chemotherapy in patients with locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastroesophageal junction (E/GEJ) receiving a trimodality treatment regimen.
Authors: Michael J. McNamara, Lisa A. Rybicki, Cristina P. Rodriguez, Gregory M.M. Videtic, Kevin L. Stephans, John Greskovich, Davendra Sohal, Sudish C. Murthy, Siva Raja, Denise I. Ives, Joanna Bodmann, David J. Adelstein
Journal: Journal of Clinical Oncology (2015)

160 Background: For patients with LRA ACA of the E/GEJ who receive pre-operative therapy, advanced pathologic stage at surgery is strongly associated with recurrence and death. Identification of such patients prior to resection, however, is problematic. Given the morbidity of esophageal resection, alternative treatment strategies may be desirable in this patient population. Methods: Between 2/08 and 1/12, 60 evaluable patients with LRA ACA of the E/GEJ enrolled in single arm phase II trial of induction chemotherapy, surgery, and post-operative chemoradiotherapy. A clinical stage of T3, N1 or M1a (AJCC 6 th ) was required for eligibility. Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and fluorouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy @ 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) given as 96 hour infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy. Updated results as of March 2014 are presented. Results: Of the 60 evaluable patients enrolled, 54 completed induction therapy and underwent surgery. Of these 54 patients, 44 patients experienced complete resolution of dysphagia, while 10 patients had persistent symptoms. PD was associated with worse distant metastatic control [HR 3.48 (1.43 – 8.43), p=0.006], recurrence free survival [HR 3.04 (1.34 – 6.92), p=0.008], and overall survival [HR 3.31 (1.43 – 7.66), p=0.005]. PD was associated with more advanced pathologic T-descriptor (pT) (p=0.048) and N-descriptor (pN) (p=0.002), a greater median number of involved lymph nodes (3 v 1, p=0.003), and greater residual tumor viability (p=0.05). No patients with PD had pT0-T2 or pN0 disease. Of the 9 patients with pN3 disease, 5 (56%) had PD. Conclusions: PD after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes. These patients may require alternative treatment strategies. Clinical trial information: NCT00601705.
Metastatic renal cell carcinoma (mRCC): Relationship between initial non-renal RECIST-target metastases hypoxia, change after 1 month of sunitinib, and therapeutic response: An <sup>18</sup>F-MISO PET-CT study.
Authors: F. Hugonnet, L. Fournier, S. Oudard
Journal: Journal of Clinical Oncology (2010)

4626 Background: We prospectively assessed the prognostic value 18F-MISO PET-CT in patients (pts) with mRCC before primary sunitinib treatment and after 28 days of treatment (4 weeks on, 2 off). Methods: Non-renal targets were defined at inclusion by CT-scan and progression evaluated according to RECIST criteria at 1 and 6 months. Target metastasis hypoxia was defined visually or by the target to blood (B) ratio (T/B) calculated as the ratio of tumour maximal standard uptake value (SUV) to the circulating blood maximal SUV computed on a standard region of interest defined over thoracic aorta. Threshold value was mean circulating blood SUV value + 1 standard deviation. Change in tumour hypoxia was defined for each patient by the difference of the median value of T/B. PET- CT data were recorded by two observers blinded to clinical and radiological data Results: From 2006 to 2009, 46 patients were prospectively included (41 males, 62.4 ± 10 years, number of RECIST target metastasis sites/pt n=4 ± 2.6, median follow-up: 19 months), 178 RECIST-target metastases were evaluated and hypoxia was present in 72 (24 pts). One month later, tumour hypoxia was reduced in 70 initially hypoxic targets (22 patients) while an increase in tumour hypoxia was observed in only 2, and T/B ratio significantly decreased among hypoxic RECIST-target metastases (2.1±0.96 to 1.62±0.93, p<0.001), but not in non-hypoxic ones (0.99±0.68 to 0.90 ± 0.50; p=0.20). Changes in tumour hypoxia within one month of sunitinib were not predictive for major events occurrence. In patients harboring no hypoxia on targets, compared to others, we observed a non significant tendency risk reduction of both 6-month progression (RR= 0.51, 95% CI: 0.13 to 1.99) and death (RR=0.48, 95% CI: 0.15 to 1.48). Adjustment on age and median diameter lesions did not change results. Conclusions: Sutininib reduces hypoxia in initially hypoxic non- renal RECIST-target metastases but not in non-hypoxic RECIST-target metastases. There is some evidence that this is linked to a lower risk of progression and death. No significant financial relationships to disclose.
Isolation and analysis of circulating tumor cell samples from both spiked analytical sources and patients with renal cell cancer and prostate cancer.
Authors: Robert J. Amato, Kevin P Rosenblatt, Mehdi Dehghani, Glauco R Souza, Reynolds Brobey, Cristian Ionescu-Zanetti, Jeff Jensen, Hubert Tseng
Journal: Journal of Clinical Oncology (2016)

584 Background: Tumor genotyping using fluid samples such as blood can potentially allow tracking of dynamic changes in mutational profiles over time and allow better access than biopsies. We present a method to detect somatic mutations from a blood draw, where circulating tumor cell (CTC) enrichment above 10% of total cell numbers allows the use of standard gene panels typically used to analyze tissue-based biopsies. Methods: Analytical samples were obtained from 9 prostate cancer (PC) patients and 6 renal cell cancer (RCC) patients, followed by CTC enrichment using the IsoFlux System. Cells were lysed and DNA amplified by whole genome amplification (WGA) using the NGS Kit (Fluxion Biosciences) and quantified via qPCR. Samples were enumerated to determine CTC load, with CTCs defined as CK+, CD45- nucleated cells (DAPI+). Next-generation sequencing was performed using 3 targeted cancer panels on the Ion torrent PGM platform: the Ion ampliseq cancer hotspot panel (50 genes; 6 PC samples), the Oncomine (143 genes; 3 PC samples), and a 29-gene panel of actionable mutations in RCC (6 samples). Data was analyzed using a customized variant calling/filtering pipeline based on standard alignment and variant calling tools. Variant filtering and functional interpretation was performed using VarSeq. All data was analyzed in a blinded manner. Results: Our method was able to isolate CTCs from all patient samples. Whole genome amplified DNA concentration was at a range of 25-164 ng/µL (median, 69) in PC and 29-180 ng/µL (median, 69) in RCC. CTCs were recovered in 2.9-33.7% (median, 10.5%) of PC samples and 1.9-33% (median, 14.5%) of RCC samples After WGA, we found 1 variant/sample using hotpot, 12/sample using Oncomine, and 3/sample using the RCC panel. Conclusions: Our assay consistently detected somatic variants from blood draw using standard gene panels in both PC and RCC. Obtaining repeat tumor biopsies from patients during treatment and/or at time of progression is both challenging and impractical from a clinical perspective. Our assay provides molecular characterization using standard blood draws and will be prospectively validated in clinical trials.