tbuckley/cabot-search huggingface dataset:
Drug pathway–associated gene polymorphisms in patients with advanced non-small cell lung cancer receiving first-line platinum-gemcitabine combination chemotherapy: A prospective multicenter observational study.
Authors: M. Joerger, S. A. Burgers, P. Baas, E. F. Smit, T. J. Haitjema, M. P. L. Bard, V. D. Doodeman, P. H. M. Smits, A. Vincent, A. Huitema, J. H. Beijnen, J. H. M. Schellens
Journal: Journal of Clinical Oncology (2011)

7536 Background: We assessed the impact of gene polymorphisms on clinical outcome in advanced non-small cell lung cancer (NSCLC) patients receiving platinum-gemcitabine chemotherapy (PG). Methods: 137 patients with stage IIIB/IV NSCLC receiving first-line PG chemotherapy (cisplatin in 74%, carboplatin in 26% of patients) were included. Mutations in 15 genes were analyzed from peripheral blood, and genotypes were compared with progression-free survival (PFS), objective response rate (ORR), overall survival (OS) and toxicity. Results: Median PFS was 5.8 months, median OS 10.2 months; 44 patients (32%) had a partial treatment response. In the adjusted model, carriers of the ERCC1 T-allele had a lower PFS compared to carriers of the CC-genotype (HR 1.62, 95%, p=0.05). Carriers of the ERCC1 CC-genotype had a higher ORR compared to carriers of the T-allele (52% vs. 29%, p=0.02). The GSTP1 GG-genotype was associated with severe platinum-associated polyneuropathy (p=0.01). ERCC1 (HR 1.54, 95% CI 1.00-2.39, p=0.05), XPD10 (HR 0.64, 95% CI 0.42-0.98, p=0.04) and XRCC1 (HR 0.51, 95% CI 0.29-0.91, p=0.02) were independently associated with OS. Conclusions: This study supports the potential predictive value of the ERCC1, XRCC1 and XPD10 germline polymorphisms in patients with advanced NSCLC receiving platinum-based chemotherapy. Non platinum-containing chemotherapy in carriers of the ERCC1 T-allele, the XRCC1 A-allele and the XPD10 G-allele may be considered and could be subject of further studies. Multivariate model for progression-free survival. Progression-free survival Parameter or genotype Patients % HR 95% CI Log-rank P ERCC1 codon 118 CC-genotype 25 18 Ref. CT or TT 112 82 1.62 1.01-2.61 0.05 XPD10 codon 312 GG-genotype 53 39 Ref. GA or AA 84 61 0.92 0.63-1.34 0.66 Stage IIIB 42 31 Ref. IV 95 69 0.81 0.55-1.18 0.27 ECOG PS 0 52 38 Ref. 1 or 2 82 62 1.52 1.05-2.19 0.03 Smoking habit Never-smoker 23 17 Ref Ever-smoker 114 83 2.28 1.40-3.71 <0.01
Comparison of older adult symptom occurrence rates in a geriatric-oncology clinic with meta-analysis for adults receiving chemotherapy.
Authors: Marie Anne Flannery, Allison Magnuson, Joseph John Guido, Luke Joseph Peppone, William Dale, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2015)

102 Background: The majority of cancers occur in older adults, yet there is limited information on their symptom experience because they are under-represented in studies. To address this gap we examined registry data from two partnered geriatric oncology clinics, our aims are to: 1) identify older patients’ symptom occurrence rates and 2) compare symptom occurrence rates to published norms for adults with cancer. Methods: At presentation, patients completed the MD Anderson Symptom Inventory with symptoms coded as present or absent. Prevalence rates were compared to rates from a meta-analysis (Reilly et al., 2013) of adult cancer patients receiving chemotherapy which included pooled data from 21 studies (age M = 58 years, Range 118 = 97 years.) Differences were tested with Chi-Square. Results: As compared to published data, older patients (N = 291, M = 80.6 years, SD = 6.47, 52% &gt; 80 yrs.) reported higher rates for the following symptoms: drowsiness (65% vs. 43%), trouble remembering (60% vs. 44%), distress (50% vs. 41%), sadness (49% vs.34%) (p’s &lt; .01), and dry mouth (55% vs. 48%, p = .03). Lower rates were reported for nausea/vomiting (23% vs 40%/ 13 vs 27%, p’s &lt; .001). There was no significant difference for the rates of fatigue (60%), difficulty sleeping (52%), pain (50%), decreased appetite (49%), dyspnea (48%), and numbness/tingling (38%). Conclusions: Older adults referred to specialized geriatric oncology clinic present with multiple symptoms. These patients had a mean age of eighty, may reflect the frail and vulnerable and were not often receiving active treatment. Results reinforce that it is especially important to assess and intervene on cognitive and psychological status in older patients. Nausea/Vomiting were less common in older adults perhaps due to lower chemotherapy rates. Limitations exist as we were not able to control for other factors affecting symptoms in the analysis. Nonetheless, results are consistent with older adults reporting many symptoms at a similar or higher rate than prior studies including all adults receiving chemotherapy. Increased study of the symptom experience in older oncology patients is critical to advance palliative care and symptom science.
Risk factors for survival in early T stage gastric cancer.
Authors: Naruhiko Ikoma, Elena Elimova, Mariela A. Blum, Jaffer A. Ajani, Y. Sabrina Chiang, Keith F. Fournier, Paul F. Mansfield, Brian D. Badgwell
Journal: Journal of Clinical Oncology (2016)

162 Background: Early T stage gastric cancer in the West is rare, with limited data to guide treatment decisions. The purpose of this study was to identify clinicopathologic factors associated with survival in early T stage gastric adenocarcinoma. Methods: The medical records of 8,260 patients with gastric or gastroesophageal adenocarcinoma presenting to MD Anderson Cancer Center (1/1995 to 12/2013) were reviewed to identify those who underwent gastrectomy with a pathological diagnosis of T1 or T2 adenocarcinoma. Associations between clinicopathologic factors and overall survival were examined with Cox Regression model. Results: We identified 121 patients with T1 or T2 tumors (49 [40.5%] T1a, 49 [40.5%] T1b, and 23 [19.0%] T2) who underwent R0 resection without neoadjuvant treatment. Mean age was 62 years, and 53% were male. Races included 53% Caucasian, 9% African-American, 17% Hispanic, and 22% Asian. Tumor locations included 10% in the esophagogastric junction and 49% confined in the antrum. Of the 121 study patients, 55% underwent extended lymph node dissection (D1+/D2) and 60% had more than 15 lymph nodes examined pathologically. Pathological analysis showed 77% of patients with poorly differentiated tumors and 27% were positive for lymph node metastasis. Postoperatively, 12% underwent adjuvant chemotherapy. The median follow-up was 5.7 years, and overall 5-year survival was 89% (98%, 93%, and 66% in T1a, T1b, and T2, respectively). Univariate analysis revealed higher risk of death in patients with T2 tumors and African-American race. N stage did not reach statistical significance for survival (HR 3.6, 95% confidence interval 1.51-8.79; p = 0.07). On multivariate analysis, T2 stage was the only variable associated with survival (HR 2.8, 95% confidence interval 1.11-7.12; p = 0.03). Conclusions: In patients with T1 or T2 stage gastric cancer, T stage was associated with diminished survival, whereas nodal status was not. Additional studies focused on patients with early-stage gastric cancer in Western populations are needed to determine which patients would benefit from preoperative or adjuvant therapy.
Clinician assessment of potentially avoidable hospitalization in patients with cancer.
Authors: Gabriel Brooks, Hajime Uno, Joseph O. Jacobson, Deborah Schrag
Journal: Journal of Clinical Oncology (2014)

4 Background: In patients with advanced cancer, acute hospitalization accounts for nearly half of all medical spending. Prior research has suggested that many hospitalizations in cancer patients are potentially avoidable, however the perspectives of clinicians directly involved in patient care are not known. Methods: We studied hospital admissions to an inpatient medical oncology service among patients with solid tumor malignancies. For each hospitalization, we interviewed three clinicians from the medical team: the outpatient medical oncologist, the inpatient attending oncologist, and the inpatient resident physician or physician assistant. Respondents were asked to identify whether or not each hospitalization was potentially avoidable (‘probably’ or ‘definitely’ avoidable vs. ‘definitely not’ or ‘probably not’ avoidable). The primary outcome was the proportion of hospitalizations identified as potentially avoidable by two or more of the three clinicians. Results: Complete clinician interview data were collected for 103 of 132 eligible hospitalizations (78%). The median age at hospitalization was 64 years, and 79% of hospitalized patients had metastatic cancer. The most common cancer sites were the lung, breast, and colorectum. 18% of hospitalizations were rated as potentially avoidable by the outpatient oncologist, 28% by the inpatient oncologist, and 30% by the inpatient resident or physician assistant. 24 hospitalizations (23%) were identified as potentially avoidable by two or more clinicians, but only 2% were identified as potentially avoidable by all three clinicians. Hospitalizations were more likely to be perceived as potentially avoidable when psychosocial factors contributed to the reason for hospital admission (OR 2.9, 95% CI 1.2-7.3). Median length of stay was shorter for potentially avoidable hospitalizations (2 vs. 4 days), but rates of death and readmission within 90 days did not significantly differ following potentially avoidable vs. other hospitalizations. Conclusions: A substantial proportion of hospitalizations in patients with cancer are perceived as potentially avoidable by clinicians who are directly involved in patient care.
Changes in management and survival outcomes for patients receiving gene-expression-based tissue-of-origin test results for difficult-to-diagnose primary cancers.
Authors: John C. Hornberger, Gauri R. Varadhachary, Hialy R Gutierrez, William David Henner, Shawn Becker, Mahul Amin, J. Scott Nystrom
Journal: Journal of Clinical Oncology (2012)

397 Background: An important step for a novel test is assessing its clinical utility and real-world effect on diagnosis and patient management. This report describes completed results of a cohort of physicians who have ordered a gene expression profile assay for identification of tumor tissue of origin (Pathwork Tissue of Origin Test) for patients with difficult-to-diagnose primary cancers and their subsequent treatment and survival. Methods: The IRB-approved registry collected data from participating physicians who have ordered the Tissue of Origin test. A detailed interview was conducted using both a web-based questionnaire and a confirmatory telephone interview with the physicians. Chart survey included collection of data on patient demographics, diagnostic procedures including imaging and immunohistochemistry as well as therapy. The physicians were queried regarding their working diagnoses and treatment recommendations prior to and after Tissue of Origin Test result availability. Date of death was also obtained with a minimum of one year follow-up from date of biopsy. Results: One hundred seven patients (61 women) have been studied and 65 participating physicians have completed the interview. Results indicate that most patients underwent extensive evaluation (≥ 10 IHC) prior to gene expression analysis. After receiving test results, physicians changed the primary site diagnosis for 53 patients (50%, CI [43,58%]; p&lt;.001) and changed the treatment management for 72 patients (65%, CI [58%,73%]; p&lt;.0001). At last follow-up, 69 patients had died with a median survival of 426 days. More than 30% of patients were alive at 1000 days. Conclusions: This registry study confirms that in patients with difficult-to-diagnose primary cancers, extensive baseline diagnostics are common and less than half of the patients have an established working diagnosis. Results indicate that the Tissue of Origin Test led to a change in working diagnosis and changed treatment recommendations in over half the patients. Survival outcomes compare favorably to historical controls in treatment trials where median survival is generally less than one year.
Correlation of circulating tumor cells in SCCNH patients to cancer reoccurrence using a negative enrichment technology.
Authors: K. Jatana, P. Balasubramanian, J. C. Lang, T. N. Teknos, D. E. Schuller, J. J. Chalmers
Journal: Journal of Clinical Oncology (2011)

5511 Background: The currently accepted definition of CTCs are cells that have: a nuclei, cytokeratin+ EpCAM+, and CD45-. Emerging evidence suggests that other rare circulating cells are present in the blood of metastatic cancer patients including CD45+ cytokeratin cells. A negative depletion process to isolate and quantify circulating tumor cells from the blood of head and neck cancer patients, using immunomagnetic separation was developed and currently be validated on a number of solid tumors, including SCCHN. Correlation of number of CTCs, tumor site, tumor stage, nodal status, smoking/alcohol abuse, histopathological characteristics, and clinical outcome was made. In addition, a subgroup of patients had blood collected immediately before and immediately after surgical resection to investigate any differences in the number of CTCs present. Methods: Prospective clinical follow-up study of 50 patients diagnosed with SCCHN undergoing surgical intervention had peripheral blood examined for the presence of CTCs. Five to 9 mL of peripheral blood was processed using previously described negative depletion enrichment with immunomagnetic tagging and removal of CD45 positive cells (Jatana et al. 2010). Subsequently, the cells were stained for cytokeratin. In addition, in some samples, other markers were targeted including vimentin, EGFR, and CD44. Results: With a mean follow-up of 24 months, data suggests that patients with detectable CTCs in the peripheral blood had a significantly reduced probability of disease-free survival (p=0.01). No correlation between the presence of CTCs with regard to tumor site, tumor stage, nodal status, smoking/alcohol use, and histopathological characteristics was observed. In a subgroup of 25 patients who had 2 consecutive samples taken immediately before and after resection, 64% of patients had an increase in number of CTCs after resection. We also identified a number of potential CTC, or cancer associated circulating cells of interest, including cells which are cytokeratin negative, vimentin positive and EGFR positive. Conclusions: Our initial data suggest a potential, important correlation between CTC and patient outcome and justifies further study.
Sunitinb-induced hyperlipidemia in patients with metastatic renal cell carcinoma.
Authors: V. Baldazzi, R. Tassi, A. Lapini, M. Carini, R. Mazzanti
Journal: Journal of Clinical Oncology (2011)

e15106 Background: Sunitinib malate is a tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). Hyperlipidemia is not described among patients on sunitinib; however, it may induce an hypothyroid state, possibly causing an increase of serum lipids. Here we describe the occurrence of hyperlipidemia in patients receiving sunitinib for mRCC. Methods: Between July 2008 and November 2010, we prospectively evaluated serum triglycerides and cholesterol in 25 patients receiving sunitinib for mRCC (50 mg daily, according to classic 6-week schedule). Median patients age was 62.9 year-old. On average they received sunitinib for 7.2 cycles. Serum lipids and thyroid function were measured before the beginning of treatment and at the end of each sunitinib ON period. Results: At baseline median serum level of triglycerides was 141.78 mg/dl (± 22 mg/dl, 95% CI) and median cholesterol was 196.8 mg/dl (± 21.8 mg/dl, 95% CI). During sunitinib administration 16 patients (64%) presented an elevation of serum lipids. These abnormalities usually developed within 2 cycles (range 1-3 cycles). In these patients, a maximum increase of median triglycerides and cholesterol of 160% and 36.1% respectively was observed. We did not observed a relationship between hyperlipidemia and hypothyroid state.Overall, at second cycle an increase from baseline of median serum triglycerides of 67.7% (237.57 mg/dl; ± 52.4 mg/dl 95% CI) was observed, while at fourth it resulted of 46.9% (208.27 mg/dl; ± 58,18 mg/dl 95% CI) and of 95.6% at sixth (277.22 mg/dl; ± 65,35 mg/dl, 95% CI). Median serum cholesterol increased of 8.7% from baseline at second cycle (214.1 mg/dl; ± 24.1 mg/dl 95% CI), of 4.5% at fourth (205,8 mg/dl; ± 22,5 mg/dl 95% CI) and 9.8% at sixth (216,1 mg/dl; ± 18 mg/dl 95% CI). Conclusions: Hyperlipidemia develops among patients on sunitinib. This is a side effect described with mTOR inhibitors, other drugs prescribed sequentially to sunitinib in mRCC patients. Therefore, an elevation of triglycerides and cholesterol may persist for a long time in those patients. We recommend a careful monitoring of serum triglycerides and cholesterol among patients on sunitinib.
Efficacy and safety of bendamustine (BDM) in patients (pts) with mantle cell lymphoma (MCL).
Authors: P. J. Hosein, S. Warsch, A. A. Alizadeh, I. S. Lossos
Journal: Journal of Clinical Oncology (2011)

e18562 Background: BDM is approved in the United States for relapsed indolent lymphoma. However, the prospective study establishing the BDM monotherapy indication did not include any MCL pts (Friedberg, JCO 2008). Another study of rituximab plus BDM for relapsed indolent lymphomas included only 12 MCL pts (Robinson, JCO 2008). Herein we report our experience with BDM specifically in MCL pts. Methods: We retrospectively reviewed the records of all MCL pts who were treated with BDM at 3 centers. Demographic, clinical, toxicity, response and survival data were collected. The primary endpoint was overall response rate (ORR) and secondary endpoints were overall survival (OS), event-free survival (EFS) and safety. Results: Between 11/2008 and 12/2010, 21 MCL pts received BDM, 4 as frontline treatment and 16 for relapsed disease. The median age was 57 years (range 42-86) and 95% had stage IV disease. The most common regimen was rituximab 375mg/m2 on day 1 and BDM 100mg/m2 on days 1 and 2, every 28 days. A median of 5 cycles were given per patient (range 1-6). There were 10 complete responses (CR) and 6 partial responses (PR) with an ORR of 76% (95%CI 58-94%). After a median follow-up of 5.7 months (range 0.3 – 24 months), the median EFS and OS were not reached. The Kaplan-Meier estimated 2-year EFS and OS was 63% (95%CI 48-77%) and 72% (95%CI 60-85%) respectively. Grade 3 or 4 neutropenia, anemia, thrombocytopenia and neutropenic fever occurred in 29%, 5%, 24% and 10% respectively. Severe non-hematological toxicities included one case of herpes zoster during therapy and one case of progressive multifocal leukoencephalopathy (PML) occurring 10 months after completion of therapy. Conclusions: BDM in combination with rituximab had a high response rate, with 48% CR’s, in this study of predominantly relapsed/refractory MCL pts. The hematological toxicities were expected and manageable. There was one case of PML, which has not previously been described with BDM, but this patient was also treated with rituximab which is associated with PML. BDM appears to be a good salvage agent for MCL.
Ten-year results of the Lyon R96-2 randomized trial in distal rectal cancer: Radiation dose escalation to increase organ preservation.
Authors: Jean-Pierre Gérard, Cecile Ortholan, Olivier Chapet, Pascale Romestaing
Journal: Journal of Clinical Oncology (2012)

556 Background: This trial was designed to test the role of a radiation dose escalation to increase conservative treatment in distal rectal cancer. The early results showed a significant increase of sphincter saving surgery (Gerard JP et al. J Clin Oncol. 2004;22:2404-2409). We present here clinical results with a 10 years follow up. Methods: Between 199- and 2001, 88 patients were included. Inclusion criteria were: adenocarcinoma of the distal rectal, T2-3 N0 M0 less not exceeding half circumference. Treatment allocation was betweeen 1) external beam radiotherapy(EBRT) (39 Gy/13 fractions/17 days) followed 6 weeks later by surgery. 2) same EBRT with Contact X-Ray 50 Kv boost (CXRT) (90 Gy /3fr/4 weeks). A careful evaluation of the clinical response was performed with digital examination and rigid rectoscopy one week before surgery. Type of surgery was left to the surgeon decision. Results: Median follow-up was 132 months. At 10 years there was no difference between both groups for overall survival and local recurrence but significantly less colostomy in the CXRT group (table). In patient with cCR the cumulated rate of colostomy was 17 % vs 42 % with cPR and 77 % with no response (p=0.014) out of 11 pts in cCR with EBRT + CXRT, 9 were treated with organ preservation (RT alone : 6, transanal local excision 3). Anorectal function was good or excellent in all these 9 patients. Conclusions: After 10 years follow up increased preservation of the anal sphincter due to CXRT has no detrimental effect on local control and survival. These results stress the importance to achieve a clinical complete response (cCR) in order to modify the surgeon decision and to increase the chance of organ preservation with a well preserved function. [Table: see text]
Cereblon Is Downregulated By Promoter Nucleosome Occupancy in Acquired IMiD Resistance: The Potential of IMiD Resensitization By Epigenetic Therapy
Authors: Konstantinos Dimopoulos, Peter Gimsing, Gangning Liang, Kirsten Grønbæk, Alexandra Helbo Søgaard, Ranjani Lakshminarasinham
Journal: Blood (2016)
A national survey on patients’ enrollment rate in oncology clinical trials: The French experience.
Authors: Iris Pauporte, Valerie Thibaudeau, Fabien M. Calvo, Agnes Buzyn
Journal: Journal of Clinical Oncology (2013)

e17567 Background: The rate of patients enrolled in clinical trials (CT) is one of the main indicators of clinical research and care activity. The successive French Cancer Plans (2003-2007 and 2009-2013) aimed at quantifiable targets of patients to be enrolled in high-quality clinical trials. To help investigators achieving this objective, a substantial financial support for clinical research associates (CRA) recruitment was given to University Hospitals (UH), Comprehensive Cancer Centers (CCC) and public or private community hospitals (CH). In the meantime, significant public investment was allocated to competitively selected academic projects through the Clinical Research National Program. Methods: From 2006 to 2011, we carried out annual national surveys on clinical research activities in oncology in France. A questionnaire was sent to cancer care institutions. Number of CT open for enrolment, number of CT sponsored by the institution, number of patients enrolled and human resources (CRA) were collected. Academic and industry-sponsored trials were analyzed separately. Results: We showed that the number of patients enrolled in CT increased continuously over this period: from 21,500 in 2002 to 35,400 in 2011 (+47%). Based on these figures and assuming that there were 420,000 to 472,000 patients eligible for CT over this period, the enrolment rate for patients in CT is estimated to be 7.5 to 8.5% in 2011 versus 5.8 to 6.7% in 2003. Nearly 80% of all enrolled patients were recruited in academic CT; over 75% of patients in therapeutic trials. UH and CCC equally contributed for 80% of enrolment, CH for the residual 20%. At last, the number of CT increased by more than 35% over the same period, while the number of CRA was multiplied by 3 over the French territory. Conclusions: Our results show that public intervention for improving enrolment to cancer CT seems to be efficient. Other types of intervention are being considered, i.e., targeted on investigators, on patients, or on both. Future work should also consider the impact of CT enrolment on patients’ outcome.