tbuckley/cabot-search huggingface dataset:
Symptom burden, health-related quality of life, and treatment preference over time as reported by patients with metastatic colorectal cancer (mCRC).
Authors: Amy Little Jones, Nrupen Anjan Bhavsar, Amy Pickar Abernethy, Yousuf Zafar
Journal: Journal of Clinical Oncology (2015)

82 Background: Clinicians have difficulty predicting longitudinal changes in patient symptom burden and quality of life, and then how those changes might affect treatment preference. The primary aim of this pilot study was to investigate how self-reported symptom burden, quality of life, and treatment preference change over time in mCRC patients with limited life expectancy. Methods: Eligible mCRC patients had incurable disease, received chemotherapy at Duke or Duke Raleigh, were &gt; = 18 years old, and spoke English. Patients were surveyed at each clinic visit and followed for up to 3.8 years on study. Measures included FACT-C (Functional Assessment of Cancer Therapy-Colorectal), PCM (Patient Care Monitor; a validated, 87-item review of systems survey; items measured on a 0-10 scale), and QQQ (Quality-Quantity Questionnaire; a validated, 8-item measure of cancer patient preference for quantity vs. quality of life; items measured on a 1-5 Likert scale). Demographic, disease, and treatment data were abstracted from the medical record. Results: The 56 patients were primarily male (68%) and Caucasian (79%) with a mean age of 55 at diagnosis of metastatic disease. Patients answered surveys a mean of 6.8 times each, with a median 364 days between first and last surveys. Over time, patients reported most symptoms improved or stayed the same (72%, n = 63 symptoms). Mean symptom scores that improved the most from first to last survey were fatigue (3.92 to 3.03) and nausea (2.1 to 1.4), while pain (1.9 to 2.5) and cough (0.4 to 0.7) worsened the most. Decision making about treatment preference also did not change over time, with mean QQQ scores from first survey (22, n = 28) to last survey (22, n = 16) remaining stable. Mean QQQ length and quality scores likewise were unchanged (12.9 to 12.8; 12.4 to 12.2 respectively). Conclusions: In this pilot study of mCRC patients with limited life expectancy, reported symptom burden scores remained stable or modestly improved over time, while preferences for quality vs. quantity of life remained stable. These findings suggest that patients with advanced cancer might perceive symptom burden differently over the course of their treatment.
Value of quantitative DNA fingerprinting in classification of second breast tumors and association with outcome.
Authors: B. L. Schlechter, P. S. Larson, Q. Yang, R. Klett, K. Armstong, A. de las Morenas, C. L. Rosenberg
Journal: Journal of Clinical Oncology (2010)

10552 Background: Management of second breast tumors is challenging. Recent data suggest that second breast tumors may be associated with worse outcomes compared to initial tumors, implying that some second tumors may be recurrences or metastases (mets). We hypothesize that quantitative DNA fingerprinting may improve classification of second breast tumors as independent primaries vs mets, affecting prognosis and treatment. Methods: We modified our published DNA fingerprinting assay into a high throughput platform to generate scores quantifying genetic differences between breast tumors. Higher scores reflect difference. With IRB approval, we collected samples and data from 34 patients (pts): 20 had ipsilateral lymph node (LN) mets and 19 had > 1 breast tumor. We modeled independent primaries using pairs of tumors from different pts. We modeled mets using pairs of tumors and LN mets from the same pt. We generated a receiver operator curve (ROC) of the scores to classify any tumor pair as independent primaries, mets, or indeterminate. We then classified tumor pairs from pts with > 1 breast tumor and followed them until disease progression. Results: We performed quantitative DNA fingerprinting on 181 tumor and LN mets samples. Scores of pairs of tumors from different pts (n = 420) averaged 0.606. Scores of pairs of tumors and their LN mets (n = 20) averaged -0.091. These scores differed (p < 10-25, student's T-test). Based on the ROC (area under the curve 0.975), scores > 0.227 were independent primaries and scores < 0.187 were mets with 95% sensitivity. For pts with > 1 breast tumor, clinical diagnosis of the second tumor (as independent primary or met) was often indeterminate (11/19 cases, 58%) and did not predict outcome. Genetic scoring decreased indeterminate cases (2/19 cases, 11%). Kaplan Meier analysis at 60 months suggested that pts with second tumors genetically classified as an independent primaries progressed later (47 vs 25 months), although this did not reach significance (p = 0.21, log rank test). Conclusions: Quantitative DNA fingerprinting improves classification of second breast tumors into independent primaries vs mets. With further refinement, this classification may also predict progression. No significant financial relationships to disclose.
The Small Molecule CHK1/CHK2 Inhibitor PF-0477736 (Pfizer) Demonstrates Single Agent Activity and Synergizes with Chemotherapy in Diffuse Large B-Cell Lymphoma
Authors: Enrico Derenzini, Ilaria Iacobucci, Elisa Brighenti, Federica Cattina, Richard Eric Davis, Stefano Pileri, Giovanni Martinelli, Michele Baccarani, Pier Luigi Zinzani
Journal: Blood (2011)
Accuracy of stereotactic vacuum-assisted biopsies in a community population.
Authors: S. D. Edwards, J. A. Vossen, M. Pronovost, P. Reeser
Journal: Journal of Clinical Oncology (2011)

106 Background: Stereotactic core biopsy in mammographically detected lesions permits histologic confirmation previous to surgery planning. We evaluated the use of stereotactic vacuum-assisted biopsy (VAB) for diagnosing suspicious, mammographically detected breast lesions in a community population. Furthermore, we determined the level of agreement between the pathology findings of VAB and the final surgical excisional biopsy. Methods: We retrospectively evaluated the results of 128 consecutive stereotactic VAB with 9-gauge needles performed over a period of 1 year in our community population. The imaging histologic concordance was ascertained for each lesion. We also evaluated concordance between VAB results and surgical excision results. Results: For the 128 patients included Breast Imaging Reporting and Data System (BI-RADS) staging showed BI-RADS 3: 4%; BI-RADS 4: 91%; and BI-RADS 5: 5%. VAB demonstrated 65 (51%) benign lesions, 31(24%) indeterminate lesions and 32 (25%) malignant lesions. The 31 indeterminate lesions included atypical ductal hyperplasia (n=13), lobular neoplasia (n=4), papillary lesions (n=12), radial sclerosing lesions (n=5), and flat epithelial atypia (n=13). Surgical excision was performed on 52 patients, and pathology demonstrated; 4 benign, 19 indeterminate, and 29 malignant lesions. There was one (3%) underestimation of an indeterminate lesion and there were 8 (25%) underestimations of malignant lesions after surgical excision. We did not observe any post-biopsy complications. Conclusions: Stereotactic VAB with a 9-gauge needle is a reliable method for diagnosing mammographically detected breast lesions in a community population.
<i>CDH1</i> structural alterations as novel prognostic biomarker in gastric cancer patients.
Authors: G. Corso, V. Pascale, D. Marrelli, H. Pinheiro, J. Carvalho, L. Garosi, R. Seruca, C. Oliveira, F. Roviello
Journal: Journal of Clinical Oncology (2011)

42 Background: Loss of CDH1 function occurs in sporadic gastric cancer (GC) progression by different molecular mechanisms. Hypermethylation and somatic mutations are considered the most frequent events. About 50% of sporadic diffuse GC shows CDH1 promoter of hypermethylation and 30% harbor somatic mutations; loss of heterozygosity (LOH) is documented in only 5% of diffuse GC cases. The present study aims to asses CDH1 alterations in 246 GC and study associated clinicopathologic features and family history of GC. Methods: Bisulphite treated tumoral DNA was used for E-cad promoter methylation. A region of 221 bps was amplified using flanking primers and direct sequencing. To search for somatic mutations the hotspot region of E-cad was amplified and directly sequenced. For LOH analysis tumor and matched normal mucosae were amplified in three microsatellite markers (D16S3025, D16S496, D16S3067) flanking the CDH1 locus. Results: Promoter hypermethylation was the most frequent event occurring in 20.7% (51 of 246) of the cases. We found 26 (10.6%) cases affected by structural alterations (three with somatic mutations and 23 with LOH). Promoter CDH1 methylation is associated with the diffuse type of GC (p = 0.017) and the presence of distant lymph node metastasis (p = 0.043). We identified association between male gender and structural CDH1 alterations (p = &lt;0.001), R1/2 radicality of resection (p = 0.015). We verified a correlation between advanced stages and CDH1 promoter methylation (p = 0.033). Kaplan-Meier survival analysis estimates that CDH1 structural alterations participate as poor prognostic factor in GC patients (p = 0.017). Conclusions: Considering the reversible nature of hypermethylation phenomena, demethylating drugs have emerged as possible chemopreventive strategies in solid tumors. Moreover, we verify that epigenetic changes of E-cadherin leading to its decrease protein expression induce an invasive behaviour to neoplastic cells; as structural alterations of CDH1 gene is assess as predictive of worse prognosis we found a new molecular biomarker of prognosis in GC that can be used to predict the clinical prognosis of the patients. No significant financial relationships to disclose.
Semi-automated validation of centralized independent review of radiological data in the OPUS trial.
Authors: Hubert Piessevaux, Binsheng Zhao, Sabine Tejpar, Lawrence H. Schwartz
Journal: Journal of Clinical Oncology (2014)

542 Background: There is increasing evidence that evaluation of tumor shrinkage on a continuous scale early on during treatment in metastatic colorectal cancer (mCRC) contains predictive information on long term treatment benefit. These findings were more specifically observed in trials evaluating addition of cetuximab to chemotherapy in first line mCRC (Piessevaux, JCO, 2013). Precise tumor measurements are necessary to implement these findings in clinical trials and practice. Independent central review has been advocated to improve the validity of the radiological measurements in clinical trials. In the phase II mCRC OPUS trial, we compared tumor shrinkage assessments given by an independent review committee (IRC) to results of a semi-automated software algorithm (SOFT). Methods: IRC measurements were performed and reported previously. SOFT requires a seed placement in a metastatic deposit. Once the seed placement is made, the computer automatically generates the boundary of the lesion and calculates the maximal diameter. The original digital radiological data from 217/337 ITT patients was available for review. Early tumor shrinkage, defined as the relative change at week 8 of the sum of the longest diameters was calculated with both measures and compared (ETS-IRC vs. ETS-SOFT). Results: The intra-class coefficient of correlation between ETS-IRC and ETS-SOFT was 0.689 (95%CI 0.604-0.759). When the population was split according to treatment group we observed the following ICC: 0.874 (95%CI: 0.815-0.914) in the chemotherapy with cetuximab arm and 0.486 (0.307-0.632) in the chemotherapy alone arm. Conclusions: Secondary independent review of radiological data from the OPUS trial showed discrepancies between IRC and SOFT. These discrepancies are potentially due to target lesion number and selection. Treatment group seems to differentiate cases more prone to discrepant review. This finding may be related to enhanced reliability when treatment effect is more pronounced. Further comparisons of traditional IRC reviews to semi-automated algorithm-based reviews with regard to outcome evaluation are warranted.
Phase II study of neoadjuvant epirubicin(E), cisplatin(C) and 5-fluorouracil(F) followed by chemoradiation with selective surgical resection/salvage for carcinomas of the esophagus and esophagogastric junction.
Authors: Joseph C Poen, Joseph W Poen, David S. Gullion
Journal: Journal of Clinical Oncology (2016)

84 Background: A subset of patients with local and regionally confined carcinoma of the esophagus (ES) or esophagogastric junction (EGJ) will not benefit from esophagectomy or esophagogastrectomy. Examples include medical inoperability and confined disease that is technically unresectable (T4 and/or N2-3). With that in mind we undertook to optimize the non-operative component of ES and EGJ cancer treatment, with surgery reserved for selected cases (medically fit, limited stage, suspicion of residual or recurrent disease). Methods: Eligible patients had AJCC stage T2-4,N0-3,M0 squamous or adenocarcinoma of the esophagus or esophagogastric junction. Medically inoperable patients were included if fit for ECF and chemoradiation (CRT) and regional disease could be encompassed within extended radiation fields. E (50mg/m2), C (60mg/m2) were given days 1,22 with F (200mg/m2) days 1-42 by protracted infusion. Subsequent CRT was C (100mg/m2) days 49,70 and F (200mg/m2) days 49-91 with 54 Gy in 30 fractions over 6 weeks. Complete responders by PET and biopsy received 2 additional cycles of ECF. Results: Between 2003 and 2015, 40 patients with non-metastatic squamous (n = 13) and adenocarcinoma (n = 27) signed informed consent. Most had clinical stage T3-4 (78%), positive regional lymph nodes (58%) and/or were felt to be inoperable due to medical comorbidities or advanced disease (50%). Dose reductions were allowed for grade II-III toxicity during ECF (13%) and CRT (33%). There was one treatment-related death (3%). At a median follow-up of 5 years, 10 patients (25%) have undergone esophagogastrectomy for persistent or recurrent disease. Median overall survival (OS) is 46 months. Survival at 1,3,5 and 7 years is 82%, 53%, 44% and 35% respectively. Conclusions: In local/regionally confined ES and EGJ cancer, long term survival with acceptable toxicity can be achieved with neoadjuvant ECF and CRT followed by selective surgical resection/salvage. This strategy appears to be appropriate for medically inoperable and technically unresectable cases, and can be considered for operable cases as well.
Carcinoma of unknown primary site (CUP): Outcomes in patients with a colorectal molecular profile treated with site-specific chemotherapy.
Authors: F. A. Greco, W. J. Lennington, D. R. Spigel, G. R. Varadhachary, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2011)

3563 Background: Molecular tumor profile assays (MTP) may predict the primary site of origin in CUP, but the impact of site-specific therapy on outcomes is undefined. Accurate identification of CUP patients (pts) with a colorectal site of origin would be expected to improve treatment results by directing the use of colorectal cancer regimens rather than empiric CUP regimens. Methods: We identified CUP patients with colorectal genetic signatures from 213 paraffin-embedded biopsies tested with mRNA-based RT-PCR molecular assays (42 from MDA tested with Veridex assay and 171 from SCRI tested with bioTheranostics CancerTYPE ID assay). Pts with a molecular colorectal cancer profile (most treated with colorectal cancer regimens) were examined for clinical features, results of standard pathologic evaluation including immunohistochemistry (IHC), response to therapy, and survival. Results: The MTP were successfully performed in 185 of 213 specimens (87%) and 32 (17%) had colorectal genetic signatures (Veridex assay 11, bioTheranostics assay 21). All 32 patients had carcinoma (29 with adenocarcinoma); colonoscopy was normal in the 30 pts studied; 29 of 32 patients (90%) had typical clinical features (liver, peritoneal, omental, pelvic, mesenteric and/or retroperitoneal metastasis) and 18 of 32 (56%) had consistent IHC profiles (CK20+ and CDX2+). 29 pts (90%) received first-line (23 pts) and/or second-line (13 pts) colorectal cancer regimens. Objective response rates to first- and second-line therapies were 69% and 54%, respectively. The median, 2-, and 4-year survivals were 22 months, 43%, and 38%, respectively. Conclusions: Pts with CUP and a colorectal molecular profile diagnosis are responsive to colorectal chemotherapy regimens. When treated with site-specific therapy, these CUP pts have a median survival (22 months) similar to pts with known advanced colorectal carcinoma and superior to the survival of CUP pts receiving empiric chemotherapy (9 months). MTP can identify CUP pts with colorectal carcinoma and therapy with colorectal chemotherapy appears to improve their outcome.
Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung: Clinicopathologic features, treatment, and survival.
Authors: Jarushka Naidoo, Kaitlin Woo, Camelia S. Sima, Natasha Rekhtman, Stacy B. Thomas, Inderpal S. Sarkaria, Charles M. Rudin, Lee M. Krug, Maria Catherine Pietanza
Journal: Journal of Clinical Oncology (2014)

e19046 Background: LCNEC is a rare thoracic malignancy, for which optimal therapy is not well-defined. We report the largest series of stage IV LCNECs, evaluating clinicopathologic features, treatment and survival outcomes. Methods: Patients (pts) with stage IV LCNEC evaluated at MSKCC from 2006-2013 were identified. Clinicopathologic and treatment data were collected. Primary endpoint was overall survival (OS) defined as time from stage IV diagnosis to death from any cause. Secondary endpoints included: disease-control rate (DCR: partial response + stable disease) and time to progression (TTP: time from stage IV diagnosis to radiologic progression). OS and TTP were analyzed by the Kaplan-Meier method. Results: 52 pts were identified (median age: 63; 62% male; 88% current/former smokers (smk). Common sites of metastasis: lymph nodes (n=29); brain (n=22); liver (n=13). 32% of pts had standard mutational analyses: 25% had KRAS mutations (n=4/17; G12D, n=2; G12C, n=1; Q61H, n=1) and no EGFR mutations or ALK rearrangements were noted. Female gender and Karnofsky performance status (KPS) were good prognostic factors for OS (p<0.05). Median OS for the entire cohort was 11.6mos. Treatment data were available for 39 pts: median lines of therapy=2 (range: 1-8). First-line regimens included: plt(platinum)/etoposide [EP] (n=25); EP/paclitaxel(n=1); cyclophosphamide/doxorubicin/E (n=1); temozolomide(alone, n=1; +bevacizumab, n =1); taxanes (alone, n=1; +plt, n=3; +plt/bevacizumab, n=1); pemetrexed (alone, n=1, +plt/bevacizumab, n=1); plt/gemcitabine (n=1); investigational therapy (n=1). There were no differences in age, gender, KPS or smk history between pts who received first-line EP vs other regimens. Similar DCRs (81% vs 77%), but worse median TTP (6.7mos vs 10.8mos, p=0.029) and OS (10.2mos vs. 56.2mos, p=.003) were seen with first-line EP vs. other regimens. Conclusions: Pts with stage IV LCNEC have poor OS, though female gender and KPS are good prognostic factors. Pts who received first-line EP relapsed quicker and had poorer OS than those treated with other regimens, indicating the need for prospective studies. Molecular analysis should be pursued, as results may help guide therapy.
Retrospective evaluation of variables affecting survival among infants with acute lymphoblastic leukemia: A single institution experience
Authors: A. R. Rosenberg, D. S. Hawkins, B. Thomson
Journal: Journal of Clinical Oncology (2008)

10044 Background: Acute Lymphoblastic Leukemia (ALL) occurring in infants (<1 year old at diagnosis) is rare and biologically distinct from ALL in older children. Single and collaborative group studies have reported long-term, event free survival (EFS) from 28% to 47%. In some series, hematopoetic stem cell transplantation (HSCT) improved survival up to 76% in first complete remission. Most HSCT data reflect survival from time of transplant, yet many infants relapse prior to HSCT. We have evaluated EFS and prognostic indicators from the time of diagnosis at a single large pediatric center where HSCT is usually part of the treatment of infant ALL. Methods: We evaluated 23 patients diagnosed with infant ALL at Seattle Children’s Hospital and Regional Medical Center between 5/31/1997 and 5/31/2007. We recorded the following variables: EFS, age at diagnosis, central nervous system (CNS) disease at diagnosis, mixed-lineage leukemia (MLL) translocation status, immunophenotype, and HSCT (in first remission with radiation based conditioning). Results: The 3-year EFS for the entire cohort was 54% (95% CI: 34–74%). Additional variables are in the table below: Conclusions: Our EFS is comparable to prior reports for infants with ALL. Selective use of HSCT may have contributed to relatively favorable EFS in our experience. Additionally, age <6 months and CD10- leukemia were not associated with a poor outcome in our small series. Infant ALL remains a high risk leukemia and further investigation is warranted to evaluate variables affecting outcome and prognosis. Variable n/total evaluable 3 year EFS p CD10 + 9/18 56% vs. 37% .401 MLL germline 13/21 62% vs 35% .78 HSCT in CR1 14/23 63% vs. 42% .2 Age <6 months at diagnosis 14/23 55% vs. 55% .7 CNS disease present at diagnosis 10/21 36% vs. 67% .098 No significant financial relationships to disclose.
Analysis and follow-up of the patients diagnosed with metastatic gastric adenocarcinoma in the Parc Taulí Hospital, Sabadell, between 2010 and 2013.
Authors: Marta Ferrer, Carles Pericay, Ismael Macias, Emma Dotor, Aleydis Pisa, Eugeni Saigí
Journal: Journal of Clinical Oncology (2016)

169 Background: The primary endpoint of this study was to know the incidence and treatment of gastric carcinoma in our area. Other secondary endpoints were percentage of treated patients, overall survival (OS), survival in subgroups, and more frequent treatments. Methods: Since 2010 to 2013 all the patients diagnosed with metastatic gastric adenocarcinoma and treated at the hospital Parc Taulí from Sabadell were registered. The clinical information was compiled and analyzed. Survivals curves were determined with Kaplan-Meier functions Results: 168 patients were studied, with 79 metastatic (47%). 56% men and median age 67 years. Localizations were gastric body 52%, gastro-esophageal junction 20%, and antrum 25%. OS of the series was 5,05 months (95% CI, 2,99-7,10). 60% of the patients were treated with first line chemotherapy (CT). From them, 42% had a second line and 25% a third line. DFS were respectively 6,62 months (4,06-9,17), 4,29 months (2,28-6,30), and 2,88 months (1,12-4,64) for every line of treatment. OS of the patients that received chemotherapy was 9.7 months (6,40-13,00). CT more used in first line were triplets of fluropyrimidines, platinum and taxanes, in 45% (21 patients). Also just fluoropyrimidines and platinum without taxanes, in 38%. As a second line the predominant CT is also platinum and fluoropyrimidines (37%), and irinotecan (30%). In third line, 50% are combinations based on irinotecan. Conclusions: The OS of the patients who received CT is significantly prolonged respect the ones who didn’t. The data obtained matches the data already published in the literature, even the more frequent chemotherapy.