tbuckley/cabot-search huggingface dataset:
Time to secondary resistance (TTSR) after rechallenge with trabectedin (T) in myxoid round cell liposarcoma (MRCLPS) patients.
Authors: Roberta Sanfilippo, Vittoria Colia, Elena Fumagalli, Rossella Bertulli, Carlo Morosi, Antonella Messina, Silvana Pilotti, Angelo Paolo Dei Tos, Alessandro Gronchi, Paolo G Casali
Journal: Journal of Clinical Oncology (2015)

10566 Background: To explore the time to secondary resistance after rechallenge with T in MRCLPS patients who were responding to T at the time of discontinuation. Methods: Since September 2002, 62 patients with recurrent myxoid liposarcoma received T at our institution. According to RECIST, 2/62 patients had a complete response (CR), 34/62 a partial response (PR) (CR+PR = 58%), 18/62 (29%) a stable disease (SD) and 8/62 (13%) a progression disease (PD). Median PFS was 14 months. Among the 54/62 patients who obtained a stable disease or a partial response after the first assessment, 28/54 interrupted treatment in absence of progression, while 26/54 patients received T until progression disease. Time to secondary resistance was defined as time from the first cycle of T to progression, whenever it occurs (including under T reintroduction). Results: In the 28 pts in whom Trabectedin was interrupted (11 for surgery of the residual disease, 1 for radiotherapy , 3 for toxicity and 13 for shared decision with clinician) , this was done after a median of 14 cycles (range = 6-21) and the median PFS was 24 months. 17 of them resumed treatment at the time of progression (F = 8, M = 9, median age = 51, range = 32-76). After rechallange, no PD was seen at first assessment, and time to secondary resistance was 48 months. In the 26 pts who went on with T until progression, PFS (i.e., time to secondary resistance) was 11 months. Conclusions: Rechallenge with T may be successful in selected patients with myxoid liposarcoma primarily responding to the drug and stopping it after a while. In this series, the choice to continue or stop the drug after response was of course at the discretion of the clinician, and selection biases are likely. Prospective studies on optimization of treatment strategy with T in MRCLPS are worthwhile.
Treatment of right-sided hepatocellular carcinoma with uni-lobar y-90 radioembolisation and induction of hypertrophy in the the contralateral left lobe.
Authors: Pierce K. H. Chow, Jin Yao Teo, John Carson Allen, David Chee Eng Ng, Richard H. G. Lo, Kiang Hiong Tay, Anthony Goh, Andrew Yu Keat Khor, Brian Goh, Foong Koon Cheah
Journal: Journal of Clinical Oncology (2013)

e15102 Background: Yttrium-90 microsphere (Y90) is currently used to treat locally advanced hepatocellular carcinoma (HCC) including those where resection is precluded because of inadequate future remnant liver. Hypertrophy of the contralateral lobe after Y90 treatment has been reported. This study aims to quantify this hypertrophy and identify factors predictive of this response. Methods: Radiological review of patients undergoing Y-90 with treatment delivered via right hepatic artery for advanced HCC between January 2008 – January 2012 was performed. Diagnosis of HCC was by AASLD criteria and patients must have at least one follow-up scan in our institution. Excluded were: tumour in the contralateral lobe, concomitant other treatment for HCC, patients enrolled in clinical trials. Pre- and post-treatment images were reviewed and volumes were measured using 3D software. Statistical analysis was conducted using SPSS version 16.0. Results: During this period 50 patients treated with Y90 for HCC had follow-up imaging at our institution. Of 37 patients with right-sided Y90 treatment, 11 had concomitant left-sided disease treated with TACE and RFA, 7 had follow-up scans of inadequate quality to perform accurate volumetric assessment, 2 had pre-treatment scans performed at another institution which were not accessible for study purposes. Seventeen (17) patients thus fulfilled criteria. Mean and median left-lobe hypertrophy were 34.2% (SD±35.9%) and 31.7% (range -19.0 – 106.5%) respectively at a median of 5 months post-treatment. Univariate analysis identified no specific pre-treatment factor predictive of the degree of left lobe hypertrophy. There were no cases of acute liver failure after administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. Conclusions: In patients with HCC receiving SIRT to the right lobe via the right hepatic artery, a significant degree of left lobe hypertrophy results. This opens the possibility of the utilisation of SIRT as neoadjuvant therapy for borderline resectable HCC, thus increasing the pool of potentially operable and curable patients.
Young-onset kidney tumors: Clinico-pathological features and subset examination of their genome-wide somatic mutations.
Authors: Gabriel G Malouf, Xiaoping Su, Roger Mouawad, Eva Comperat, Morgan Roupret, Olivier Cussenot, Jean-Philippe Spano, David Khayat
Journal: Journal of Clinical Oncology (2015)

e15576 Background: Early age of onset of 46 year or younger might be associated with hereditary renal cell carcinoma (RCC). However, the clinico-pathological features, clinical outcome and genome-wide analysis of somatic mutations in this RCC subset remains unknown. Methods: We analyzed retrospectively all clinico-pathological features of early-onset RCC treated at Pitié-Salpêtrière Hospital between 2008-2014. In a subset of 12 RCC {medullary (n = 2), oncocytoma (n = 2), clear-cell RCC (ccRCC) (n = 8), mucinous and spindle cell RCC (n = 1}), whole-exome sequencing was performed on genomic DNA derived from matched tumor-normal pairs, using Agilent human V5 capture and the HiSeq sequencing platform. Paired-end RNAseq was also carried out in the same dataset for fusion transcript detection. Results: Overall, 79 kidney tumors have been identified including 15 benign tumors and 64 malignant RCC. Six (7.6%) patients had hereditary RCC including three with Von-Hippel Lindau disease. The most frequent malignant RCC subtypes were ccRCC (n = 25), papillary RCC (n = 15) and MITF/TFE translocation RCC (TRCC) (n = 13). Ten patients (15.6%) presented initially with metastatic disease, including 5 with TRCC. Median overall survival of initially metastatic patients with malignant RCC was 28.1 months versus NR for others (p < 0.0001). Median non-synonymous somatic single nucleotide variants were 22 (range, 13-48) and 11 (range, 3-36) in ccRCC and non-ccRCC, respectively (p = ns). In three ccRCC samples arising in the context of VHL disease, no recurrent somatic mutations were identified. In four sporadic ccRCC, 3 and 2 cases showed VHL and PBRM1 mutations, respectively. In young-onset ccRCC, Ingenuity Pathway Analysis revealed enrichment of mutations in genes related to PTEN signaling. No fusion transcripts were identified. Conclusions: Our study charts the distribution of young-onset kidney tumors and reveals that TRCC display the poorest outcome. In addition, we discover that young-onset ccRCC display similar mutational signature but lower mutational load as compared to ccRCC in patients older than 46 years.
Serum mass-spectrometry test in first-line advanced NSCLC patients treated with standard chemotherapy regimens.
Authors: Francesco Grossi, Carlo Genova, Erika Rijavec, Maria Giovanna Dal Bello, Giulia Barletta, Giovanni Burrafato, Federica Biello, Claudio Sini, Julia Grigorieva, Krista Meyer, Heinrich Roder
Journal: Journal of Clinical Oncology (2014)

e19090 Background: The mass-spectrometry based serum test VeriStrat (VS) was shown to be prognostic in various therapies and predictive of differential overall survival (OS) benefit for erlotinib vs. chemotherapy (CT) in second line NSCLC setting. Performance of the test in CT is of clinical interest. We investigated the role of VS in first-line advanced NSCLC patients (pts) treated with Cisplatin (Cis) or Carboplatin (Carbo) plus Pemetrexed (P). Methods: VS classification was available for 55 eligible stage IV, pts with non-squamous histology; pts were classified as VS Good (VSG) or VS Poor (VSP), VS testing of pretreatment serum samples was done blinded to clinical data. OS and progression-free survival (PFS) were analyzed by Kaplan-Meier method and compared using log-rank p-values; Cox models were used in multivariate analysis. Association with categorical variables was analyzed by Fisher’s exact test. Results: 36 (65%) pts were classified as VSG and 19 (35%) as VSP. In the overall population, median PFS was 5.7 months (mo) for VSG vs.1.4 mo for VSP (hazard ratio (HR) 0.37 [0.19-0.72], p=0.002 ); adjusted HR (AHR) 0.38 [0.17-0.86], p=0.021). Median OS was 10.8 mo for VSG vs. 3.4 mo for VSP (HR 0.23 [0.11-0.51], p < 0.001; AHR 0.12 [0.04-0.37], p<0.001). A similar relationship was found in both treatments: In CarboP median PFS in VSG and VSP was 3.8 mo and 2.0 mo respectively (HR 0.38 [0.15-0.94], p=0.030); median OS was 10.8 mo in VSG and 3.4 mo in VSP (HR 0.26 [0.09-0.72], p=0.006). In CisP median PFS was 6.1 mo in VSG and 1.2 mo in VSP (HR 0.40 [0.14-1.12], p=0.070), median OS was 12.3 mo in VSG, 3.8 mo in VSP (HR 0.17 [0.04-0.69], p=0.005).When compared within VS groups, no statistically significant differences between CarboP and CisP was found either for PFS (VSG: p=0.508, VSP: p=0.718) or OS (VSG: p=0.466 , VSP: p=0.522). VS was significantly associated with disease control rate (p=0.003) and trended towards significance for objective response (p=0.085). Conclusions: In Platinum-based doublet CT, VSP pts had much shorter PFS and OS than VSG. The behavior was similar in CisP and CarboP arms. Further research is needed to find alternative treatments to improve outcomes for VSP pts. ClinicalTrials.gov Identifier NCT02055144.
Targeting Pre-Leukemic Stem Cells in T-Acute Lymphoblastic Leukemia
Authors: Bastien Gerby, Diogo F.T Veiga, Jana Krosl, Julianne Ouellette, André Haman, Geneviève Lavoie, Iman Fares, Mathieu Tremblay, Véronique Litalien, Elizabeth Ottoni, Milena Kosic, Dominique Geoffrion, Joël Ryan, Paul Maddox, Jalila Chagraoui, Anne Marinier, Josée Hébert, Guy Sauvageau, Benjamin H Kwok, Philippe P Roux, Trang Hoang
Journal: Blood (2016)
Understanding the symptom experience of breast cancer outpatients: The validity and utility of the M.D. Anderson Symptom Inventory (MDASI).
Authors: Tito R. Mendoza, Fengmin Zhao, Charles S. Cleeland, Lynne I. Wagner, Linda J. Patrick-Miller, Michael Fisch
Journal: Journal of Clinical Oncology (2012)

9106 Background: Breast cancer and its treatments can produce multiple symptoms that cause distress and impair function. The MDASI, a patient-reported outcome measure of symptoms (sxs) and functional interference has been validated in general oncology and has the potential to inform symptom experience and guide treatment specific to breast cancer patients (pts). Methods: The Eastern Cooperative Oncology Group (ECOG) conducted the Symptom Outcomes and Practice Patterns (SOAPP) study at academic and community medical oncology clinics and included pts with breast cancer of all stages and phases of care. At baseline and 4 weeks, pts completed the MDASI. Symptom experiences and psychometric properties of the MDASI in breast cancer pts (n = 1544) were analyzed. Results: The median age was 58 years, and the race/ethnicity included 11% black and 8% hispanic. 5% had ECOG performance status (PS) ≥2. The 5 most prevalent moderate/severe sxs reported at baseline were fatigue (31%), disturbed sleep (27%), drowsiness (21%), hair loss (22%) and dry mouth (19%); moderate/severe skin rash (6%) and vomiting (4%) were the least prevalent. At follow-up, about 1/3 of patients had moderate/severe fatigue and 19% had moderate/severe pain and distress. Internal consistency and test-retest reliability were good, with Cronbach alphas of ≥0.85 and intraclass correlations of ≥0.76 for all subscales. Among those whose PS was stable or improving, the change scores in sx severity improved most for sleep disturbance, numbness/tingling, and difficulty remembering things. Significantly higher scores and moderately large effects for the severity scale were reported by pts with poorer PS (ES=.61) and those with local/regional/metastatic disease (ES=.67). Results were similar for the interference scale. Pts whose quality of life (QOL) declined showed greater increase in severity (1.1 vs .07, p&lt;.001) from baseline to follow-up than pts whose QOL was unchanged, demonstrating sensitivity to change. Conclusions: Breast cancer pts have significant sx burden despite well-preserved PS. The MDASI is a valid, reliable, and sensitive sx assessment method for research and patient care in breast cancer outpatients.
Influence of common comorbid conditions on a 17-gene assay for prediction of adverse pathology in clinically low-risk prostate cancer.
Authors: Jennifer Cullen, Isabell Sesterhenn, H. Jeffrey Lawrence, Huai-Ching Kuo, Shiv Srivastava, Inger L. Rosner, Nan Zhang, Timothy C. Brand, Alan W Shindel
Journal: Journal of Clinical Oncology (2017)

91 Background: Well-validated molecular biomarkers can improve risk stratification in newly diagnosed PCa. It is important to demonstrate that biomarkers are not influenced by common clinical conditions. A 17-gene biopsy-based RT-PCR assay (Oncotype Genomic Prostate Score, GPS) has been validated as an independent predictor of adverse pathology and biochemical recurrence after surgery. We sought to explore the association between comorbid conditions and GPS. Methods: We examined the association between GPS and obesity (OB), diabetes mellitus (DM), hypertension (HTN), hypercholesterolemia (HC), coronary artery disease (CAD) and Low Testosterone (Low T) in a cohort of surgically treated men with clinically low-risk PCa. All men were seen and treated at Madigan Army Medical Center or Walter Reed National Military Medical Center. Diagnoses were abstracted from the electronic medical record. OB was defined as body mass index (BMI) &gt; 30 kg/m 2 . Low T was defined as total T &lt; 300 ng/mL. Student’s T test and ANOVA were used to assess differences in GPS between the groups of men with or without relevant diagnoses. Results: GPS results were available in 402 patients; 389 (97%) had BMI data. Pre-treatment serum testosterone (T) levels were available for 120 patients. There were no significant differences in mean GPS between men with or without OB, HTN, HCL, DM, and low T (p &gt; 0.05). This relationship persisted when men with no vascular risk factors were compared to men with any vascular risk factor (DM/HTN/HCL) and/or with diagnosed coronary artery disease. There was a modest but statistically significant inverse correlation between GPS and continuous serum T (r = -0.18; p = 0.049). Conclusions: Comorbidities that are common in older men with prostate cancer do not appear to influence GPS results. Although Low T was not associated with GPS, there was a weakly negative association between GPS and continuous T. This may reflect the more aggressive PCa phenotype that has been reported in patients with progressively lower serum T.
Current approaches in the treatment of malignant ascites in Germany and Austria.
Authors: Diana Lueftner, Susanne Küpferling, Gülten Oskay-Özcelik, Christian Jehn
Journal: Journal of Clinical Oncology (2013)

e20670 Background: Malignant Ascites (MA) is a common manifestation of advanced cancer associated with a poor prognosis and decreased quality of life. Currently there are no evidence based guidelines for the management of MA and only one agent is approved for its treatment. We conducted a survey with physicians throughout Germany and Austria, to get an overview of current approaches and opinions in the treatment of MA. Methods: 128 medical oncologists (MO), gastroenterologists (GE) and gynecologists (GYN) completed an electronic questionnaire consisting of 33 questions. Answers were evaluated with descriptive statistics. Results: 90% of the physicians were from Germany, 10% from Austria. 48% of those were MO, 30% were GYN and 14% were GE. Most physicians treated an average of 34 pts/year with MA. 26% of these pts suffered from ovarian, 20% from pancreatic, 17% from gastric and 14% from colorectal cancer. The majority of the physicians associated MA with poor prognosis (92%) and significant reduction in quality of life (87%). One third felt MA was a contraindication for full dosing of systemic chemotherapy. Paracentesis (P) was performed in 70% of pts with with symptom relieve and quality of life being the main reasons. Almost half of the pts required 3-5 P, 50% even more than 5 P during the course of their disease. Only 15% of pts needed multiple P per week, the majority (79%) needed the procedure either once a week or every 14 days. In 61% of pts 3-5 l ascites fluid was drained. Only in 8%, 5 l and more were removed. Volume substitution with IV albumin was performed in 40% of pts. Most pts (55%) had to stay 1-3h in a healthcare facility for the procedure. However 21% had to stay &gt; 1 day. While almost all physicians (89%) performed a P at some point in the treatment of MA, 75% felt that a systemic chemotherapy and 55% thought a concomitant diuretic therapy were a necessary adjunct. 7% of the pts received a targeted treatment with catumaxomab. Conclusions: Even though repeated P is the main pillar of treatment of MA, its effect is only temporary, must be performed multiple times, requiring hospital resources. Further treatment strategies have to be evaluated in prospective studies. Targeted therapies like catumaxomab should be integrated into these.
De novo metastatic prostate cancer: Patterns of PSA testing prediagnosis and disease characteristics.
Authors: Yasser Ged, John Patrick Greene, Hazel Murray, Eoghan Ruadh Malone, Paula Calvert, Miriam O'Connor, Anne M. Horgan, Raymond S. McDermott
Journal: Journal of Clinical Oncology (2017)

271 Background: A small proportion of men with prostate cancer (PCa) will present with metastatic disease at first presentation, termed de novo metastatic PCa. PSA screening is not a national policy, yet PSA testing is commonly performed and national guidelines are available to guide subsequent management. We sought to investigate this group of men to determine if prior PSA testing had been previously performed, and if elevated, to determine if appropriate referrals were being made. We also sought to further characterise and analyse associated risk factors. Methods: A retrospective review of pts who presented with de novometastatic PCa over a three year period was performed in three cancer centres in Ireland. Characteristics such as demographics, Gleason score, symptoms at presentation and disease volume (high v low) were obtained. PSA results done in the primary care for a period of 12-24 months and &gt; 24 months prior to diagnosis were recorded. Results: 100 pts with de novo metastatic PCa were identified between 2013 and 2015. Median age at diagnosis was 72 years (49-90), 77 pts (77%) presented with high volume disease, 11 pts (11%) had evidence of visceral metastasis with a median age of 62 years (51-72). Median PSA level at diagnosis was 106, and 91% of pts (n = 74) had a Gleason score of ≥ 8. Symptoms at presentation were evaluable in 88 pts with the majority of pts presenting with pain (n = 49, 55.6%) and lower urinary tract symptoms (n = 33, 37.5%). 22 pts (22%) had a PSA level done within 12-24 months prior to diagnosis which was higher than 4.0 ng/ml in 18 pts (82%). 57 pts (57%) had a PSA level done over 24 months prior to diagnosis which was higher than 4.0 ng/ml in 35 pts (61.4%), PSA measurement was only repeated in 18 pts (51%) out of 35 pts with high PSA levels prior to diagnosis. Having elevated PSA levels over 4.0 ng/ml within 12-24 months and over 24 months prior to diagnosis was not associated high volume metastatic disease (P = 0.88). Conclusions: A sizeable proportion of pts diagnosed with de novo metastatic PCa had PSA measurements performed more than one year prior to diagnosis which was elevated. Optimization and adherence to national guidelines regarding PSA testing is needed to decrease the number of pts diagnosed with de novo disease.
Ten-year prospective experience of gastrointestinal stromal tumors (GISTS) from the Cambridge GIST Study Group, United Kingdom.
Authors: Venkata Ramesh Bulusu, Helen Hatcher, Richard Hardwick, Nicholas Carroll, Stephanie Pursglove, Vicki Save, Peter Safranek, Helena Margaret Earl
Journal: Journal of Clinical Oncology (2013)

10541 Background: Cambridge GIST study group was formed in 2003. GIST specialist multidisciplinary team (MDT) and GIST clinic were established with central review of histology/pathology and management plans. We present our 10 year experience of a prospective database which formed the template for the United Kingdom national GIST registry. Methods: All patients (pts) who have been referred to the GIST MDT were included in the study. The following data was prospectively collected: patient demographics, presenting symptoms, site, size, histology including mutational data (where available) risk stratification of the GISTS, surgical interventions, systemic therapies, other tumours occurring in GIST pts. Results: 260 patients (pts) were reviewed in the GIST MDT. 29 pts had endoscopic/imaging diagnosis of a GIST and were not included in the final analysis. 41 pts had other tumours diagnosed when GIST was initially suspected. Histologically confirmed GISTS N=190. Male: Female 52%:48%. Median age 64 years (range 14-94), 4% &lt;40years. 84% had surgical intervention (primary or metastatectomy), 9% had resections on imatinib/sunitinib. Tumour characteristics: Site: Stomach-73%, small bowel-16%, EGIST-4%, colorectal-3%, duodenum-3% and oesophagus-1%. Size 0.1-40 cm. Histology subtype: Spindle cell =84%, mixed=12% and epitheloid=4%. Miettinen risk stratification groups: High risk=27%, intermediate risk=16% and very low risk/low risk=57%. Mutational status results in 36 pts: exon 11=64%, PDGFRA= 14%, wild type=11%, exon 9=5.5%, exon 13=5.5%. 14% of GIST pts had other tumour either prior to diagnosis or during treatment/follow up of GISTS. Conclusions: This is the first prospective regional GIST registry data from UK. Our results mirror other large prospective series. GISTS should be managed by an experienced multidisciplinary specialist team to provide a high quality patient centred service.