tbuckley/cabot-search huggingface dataset:
Biological markers to predict response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC): Ready for prime time?
Authors: M. S. Pino, A. Fabi, M. Tedeschi, M. Mottolese, P. Papaldo, P. Vici, G. Ferretti, C. Nisticò, M. Russillo, F. Cuppone, A. Di Benedetto, C. Botti, D. Giannarelli, F. Cognetti
Journal: Journal of Clinical Oncology (2011)

e11073 Background: NCT has been shown to improve disease-free and overall survival in BC patients. Predictive markers of therapeutic response need to be carefully studied in order to distinguish specific patient populations with a greater probability of response. The purpose of the present study was to evaluate whether biological markers can predict clinical (cCR) and pathologic complete response (pCR) to NCT in patients with LABC. Methods: Patients with LABC who received anthracycline- and taxane-based NCT ± trastuzumab, on the basis of the epidermal growth factor receptor 2 (HER-2) status, were included in this retrospective study. Pretreatment biopsy and matched surgery materials were used to perform immunohistochemical (IHC) studies for estrogen receptor (ER), progesterone receptor (PgR), HER-2, and Ki67 proliferation index protein expression. The association between biological markers, cCR and pCR was analyzed. Results: A total of 60 patients were studied: 42 (70%) patients had ER-, 33 (55%) had PgR-, and 32 (53%) had HER-2 positive (IHC 3+ or SISH amplified) tumors. The overall clinical response rate was 85%, with 21 (35%) patients achieving a complete and 30 (50%) a partial response, respectively. The pCR rate was 43% (n=26). In the univariate analysis, only HER-2 overexpression was predictive of cCR and pCR to chemotherapy (P=0.04 and P=0.0002, respectively). Indeed, a pCR was observed in 21 (66%) patients with HER-2 positive tumors as compared to only 5 (18%) patients with HER-2 negative tumors. A trend between higher Ki67 and pCR was also reported (P=0.08). Conclusions: We have shown that HER-2 overexpression and an high proliferation index may indeed be predictive of response to NCT.
Use of R.E.N.A.L. nephrometry scoring system to predict the functional efficacy of nephron-sparing surgery in the solitary kidney.
Authors: David D. Buethe, Sammy Moussly, Hui-Yi Lin, Xiuhua Zhao, Philippe E. Spiess, Wade Jeffers Sexton
Journal: Journal of Clinical Oncology (2012)

399 Background: Recently, the R.E.N.A.L. nephrometry scoring system was introduced to objectively describe renal masses with respect to size, the degree to which they are exo/endophytic, the nearness to the collecting system, whether they are anterior or posterior and the location relative to polar lines. It is our aim to evaluate the R.E.N.A.L. nephrometry scoring system’s ability to predict functional renal loss attributed to nephron-sparing surgery (NSS). Methods: We evaluated 42 patients presenting with either an anatomic (32) or functionally solitary (10) kidneys undergoing partial nephrectomy (PN). Each renal unit was assigned a R.E.N.A.L. nephrometry score utilizing pre-operative cross-sectional imaging. The CKD−EPI equation was applied to serum creatinine levels to generate corresponding estimated glomerular filtration rates (eGFR). The difference between the eGFR at baseline and at post-operative time points served as a measurement of renal function loss attributed to PN. Results: Forty-two patients underwent PN with mean pre-operative eGFR of 61.5 mL/min/1.73m2. The median total nephrometry score was 8, ranging from 4–10. Twenty-eight (66.7%) of the renal lesions were ≤ 4 cm, 13 (31%) were between 4 and 7 cm, and 1 (2.4%) was &gt;7 cm in diameter. The majority (54.8%) of the patients had tumors with more than 50% of tumor burden lying outside the expected renal border whereas 3 patients (7.1%) had tumors considered to be completely endophytic. Twenty-seven (64.3%) were within 4 mm of the collecting system. Tumor locations defined as: completely polar, interpolar, and completely central were assigned to 11, 15, and 16 lesions respectively. By post-operative month 6, the overall average eGFR of 53.9 mL/min/1.73m2 was significantly less (p = 0.0293) than the pre-operative value. However, we were unable to correlate change in post-operative eGFR with pre-operative total or individual R.E.N.A.L. scoring parameters. Conclusions: Neither the individual components of the R.E.N.A.L. nephrometry scoring system nor the total nephrometry score correlated with realized functional loss as assessed by eGFR in patients with a solitary kidney undergoing NSS.
Characterization of unplanned 30-day medical oncology readmissions after discharge at an academic medical center with a comprehensive cancer center.
Authors: Inga Tolin Lennes, Justin Eusebio, Nie Bohlen, Margaret Ruddy, David P. Ryan
Journal: Journal of Clinical Oncology (2016)

269 Background: Hospital readmission rate is increasingly suggested as a quality care metric. Currently there are no standard criteria for an avoidable readmission in oncology. Although patients with cancer have been identified as being at increased risk of readmission, there has been little to examine the reasons for the oncology patient readmission. The aim was to examine the profiles of patients with an unplanned readmission within 30 days after discharge by an oncology provider and to measure the unplanned 30-day readmission rate. Methods: A retrospective review of oncology provider discharge encounters resulting in a 30-day unplanned readmission during the 2012 calendar year at a tertiary hospital with a comprehensive cancer center was conducted. Planned readmissions for chemotherapy, radiation therapy, hematopoietic stem cell transplantation, dialysis, and surgical procedures, as well as readmissions for rehabilitation, hospice, and psychiatry were excluded. Medical oncologists analyzed medical records for the primary reason of readmission and if the readmission was possibly preventable. Results: Of the 2,944 admissions, a final cohort of 441 unplanned readmissions from 321 unique patients for an unplanned 30-day readmission rate of 14.9% was observed. The average age at admission was 59 (SD 15.9). The cohort was mostly male (56.9%) and White/Caucasian (84.4%). Gastrointestinal (24.0%), lymphoma (18.6%), and leukemia (17.5%) were the most common cancer types. Of those with solid tumors types (n = 225), approximately 70% had metastatic disease. The median time to readmission was 10 days and 10.7% died within 30 days of readmission. Oncology reviewers most commonly assessed that readmission was primarily due to treatment-related effects (46.7%) and the progression of disease (42.2%). Approximately 20% of 30-day readmissions were determined to be possibly preventable, representing 3% of all admissions for the year. Conclusions: Oncology patients readmitted within 30-days frequently present with complicated, advanced disease. A review by medical oncologists suggests there is margin for intervention to reduce 30-day unplanned admissions.
Interim results of a phase II study of the mTOR inhibitor everolimus in patients with pretreated metastatic gastric and esophageal adenocarcinoma.
Authors: Zev A. Wainberg, Ravi Patel, Brian DiCarlo, David J Park, Frederic C. Kass, Andre K. D. Liem, He-jing Wang, Diego Martinez, J. Randolph Hecht
Journal: Journal of Clinical Oncology (2012)

80 Background: There is increased evidence that cancers of the upper GI tract are comprised of distinct epidemiological and molecular entities that may respond differently to anti-cancer therapy in Asian patients compared to North American patients. Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR) showed clinical promise in a phase II study in Japanese patients with pre-treated metastatic gastric cancer with a disease control rate of 56% (Doi et al, JCO, 2010). This study evaluates the efficacy and safety of everolimus in patients with pre-treated metastatic gastric and esophagus cancers in a US population. Methods: Patients with advanced upper GI adenocarcinomas who experienced disease progression despite 1-2 prior regimens were treated with everolimus 10 mg PO daily. The primary endpoint was disease control rate (DCR; CR+PR+SD). Secondary end points included progression free survival (PFS), toxicity, overall survival (OS) and translational correlatives of the mTOR pathway. Results: Of the 40 patients enrolled to date, 19 have gastric, 7 have esophagus and 14 have tumors from the GEJ. 32 patients are evaluable to date: median age of 59 (range 36-79), all patients had an ECOG of 0 or 1; 11 (34%) received 1 prior regimen and 21 (64%) received 2 prior regimens. We observed 0 responses with 44% of evaluable patients having stable disease. Median overall survival was 5.6 months (95% CI: 3.2-7.6) and PFS was 1.8 months (95% CI: 1.6-2.2). 89% of all adverse events were grade 1-2, and 11% were grade 3-4. Grade 3-4 related adverse events include: fatigue (24%), thrombocytopenia (22%), anemia (9%). Updated results of translational correlatives with the mTOR pathway will be presented. Conclusions: We did not achieve the same degree of overall survival or disease control as in the Japanese study which may reflect differences in the locations of the primary tumor or underlying geographic variation. However, OS is significantly better than best supportive care reported in a recent randomized European trial (Thuss-Patience PC et al, Eur J Cancer 2011). Results of the randomized Phase III trial of everolimus vs best supportive care in this patient population are pending.
Accuracy of NaF PET/CT scan to detect bone metastases in CRPC.
Authors: Modar Alom, Ilija Aleksic, Brian Ruhle, Peter Iannotta, Colin Okeefe, Vladimir Mouraviev, David Albala, Christopher Michael Pieczonka
Journal: Journal of Clinical Oncology (2014)

186 Background: The current standard for imaging Castration Resistant Prostate Cancer (CRPC) is aimed at detecting metastatic lesions to the bones. However, discovery, validation, and implementation of new imaging modalities have fallen considerably behind that of new therapies for this population. Recent studies have shown the NaF PET/CT Scans are significantly more sensitive and accurate in detecting bone lesions than conventionally used Bone Scintigraphy with Technetium-99 (Tc-99). This study conducted retrospective analysis to compare the competence of these two methods for identifying bone metastases. Methods: We conducted a charts review of 613 patients being currently treated with androgen deprivation therapy (ADT) and identified 55 patients who obtained a Na18F PET/CT Scan. Results: The median age was 75.5 years with a range of 52-89, for our cohort. Of these 55 patients, 5 (11.9%) were determined to have metastasis with Tc-99 Bone Scintigraphy alone while 27 (49.1%) were determined to have metastases with NaF Scan (p&lt;0.005). 8 (19%) patients had equivocal findings on Tc-99 Bone Scintigraphy. Therefore, for all of them we performed NaF scan to define a bone metastatic disease that demonstrated in 5 (62.5%) cases of these as having no bone involvement and 3(37.5%) as positive for bone lesions (Table). However, data of NaF scan also indicated 5(9%) patients as having equivocal findings for metastatic disease. Conclusions: According to our data, NaF is more sensitive for detecting bone lesions (11.9 vs. 49.1%). It was also able to delineating equivocal TC-99 Bone Scintigraphy findings, where it deemed 62.5% as negative and 37.5% as positive for bone lesions. NaF PET scan is a feasible option for CRPC for detecting bone metastases, early in disease progression. With coverage of this procedure by Medicare patients have more sensitive and specific tool for early diagnosis and monitoring of treatment of CRPC. [Table: see text]
Bassoon Controls Presynaptic Autophagy through Atg5
Authors: Nathan D. Okerlund, Katharina Schneider, Sergio Leal-Ortiz, Carolina Montenegro-Venegas, Sally A. Kim, Loren C. Garner, Clarissa L. Waites, Eckart D. Gundelfinger, Richard J. Reimer, Craig C. Garner
Journal: Neuron (2017)
Everolimus plus octreotide LAR versus placebo plus octreotide LAR in patients with advanced neuroendocrine tumors: Analysis by primary tumor site from RADIANT-2.
Authors: E. M. Wolin, N. Fazio, S. Saletan, R. E. Winkler, A. Panneerselvam, L. Kvols
Journal: Journal of Clinical Oncology (2011)

4075 Background: Advanced neuroendocrine tumors (NET) arise from diverse sites of origin, including GI tract, lung, and pancreas. Nearly 50% of new NET cases are advanced, and 5-year survival rates vary, depending on the primary site of disease. In the RADIANT-2 trial, everolimus, an oral mTOR inhibitor, plus octreotide LAR (E+O) provided a clinically meaningful 5.1-month increase in median progression-free survival (PFS) compared with placebo + octreotide LAR (P+O) in patients with advanced NET (ESMO 2010 Abstract LBA8). Here we present an exploratory analysis of PFS by primary tumor site in the RADIANT-2 patient population. Methods: Patients (n=429) with well or moderately differentiated advanced NET and a history of secretory symptoms associated with carcinoid syndrome received oral everolimus 10 mg/d + octreotide LAR 30 mg intramuscularly q28d (n=216) or P+O (n=213). The primary endpoint was PFS per central review (RECIST v1.0). The primary tumor site was identified in each treatment arm. Analysis was performed to determine the association between primary tumor site and PFS. Results: Small intestine, lung, and colorectal were the primary tumor sites in 224 (111 E+O; 113 P+O), 44 (33 E+O; 11 P+O), and 39 (19 E+O; 20 P+O) patients. Median PFS was longer in the E+O arm than in the P+O arm in all three groups (Table). E+O improved median PFS compared with P+O by 4.6 months in small intestine, 8.0 months in lung, and 23.3 in colorectal subgroups. Conclusions: Everolimus plus octreotide LAR demonstrates a clinically meaningful prolongation of median PFS in patients with well or moderately differentiated advanced NET, including patients with primary tumor sites associated with a poorer prognosis, such as lung and colorectal cancer. Median PFS E+O months (95% CI) Median PFS P+O months (95% CI) HR (95% CI) P Overall 16.4 (13.67-21.19) 11.3 (8.44-4.59) 0.77 (0.59-1.00) 0.026 Small intestine n=224 18.63 (13.60-25.89) 14.03 (9.40-19.84) 0.77 (0.53-1.13) 0.092 Lung n=44 13.63 (5.55-14.29) 5.59 (2.79-27.76) 0.72 (0.31-1.68) 0.228 Colorectal n=39 29.90 (5.59-NA) 6.57 (3.02-13.04) 0.34 (0.13-0.89) 0.011
Subgroup analyses of Japanese patients from the PREVAIL trial of enzalutamide (ENZA) in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC).
Authors: Go Kimura, Junji Yonese, Takashi Fukagai, Tomomi Kamba, Kazuo Nishimura, Masahiro Nozawa, Harry H. Mansbach, De Phung, Tomasz M. Beer, Bertrand F. Tombal, Takeshi Ueda
Journal: Journal of Clinical Oncology (2015)

265 Background: In PREVAIL, an international phase 3 randomized trial, treatment with ENZA decreased the risk of radiographic progression or death by 81% and the risk of death by 29% compared with placebo. We evaluated efficacy, safety and pharmacokinetic exposure with ENZA in the Japanese subgroup of patients participating in PREVAIL. Methods: Asymptomatic or mildly symptomatic chemotherapy-naïve patients with mCRPC progressing on androgen deprivation therapies were randomized 1:1 to ENZA 160 mg or placebo until discontinuation upon radiographic progression or initiation of chemotherapy. Continued androgen-deprivation therapy was required. Coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS). Prostate-specific antigen (PSA) response was defined as a confirmed ≥50% reduction from baseline to nadir. Results: A total of 1,717 patients (ENZA: 872, placebo: 845) were randomized in PREVAIL, of which 61 patients were Japanese (ENZA: 28, placebo: 33). The trial was halted after a planned interim analysis at which hazard ratios calculated for OS (0.71; 95%CI: 0.60-0.84) and rPFS (0.19; 95%CI: 0.15-0.23) showed significant benefit of ENZA vs placebo. Hazard ratios for OS and rPFS in Japanese patients were 0.60 (95%CI: 0.20-1.78) and 0.29 (95%CI: 0.030-2.95), respectively. Time to chemotherapy was delayed from a median 10 months on placebo vs not yet reached on ENZA, with a hazard ratio of 0.46 (95%CI: 0.22-0.96). PSA responses were more common in Japanese patients receiving ENZA (61%) vs placebo (21%) (treatment effect = 39.5%; 95%CI: 16.7%-62.3%). Plasma concentration of ENZA was slightly higher in the Japanese subgroup: geometric mean C min = 13.8 µg/mL vs 12.3 µg/mL in the non-Japanese cohort at 13 weeks. In the Japanese subgroup adverse events (AEs) ≥ Grade 3 were reported by 9/28 patients (32%) on ENZA vs 13/33 patients (39%) on placebo. Treatment-related AEs ≥ Grade 3 were rare: in the ENZA arm (1/28; 3.6%) and in the placebo arm (2/33; 6.1%). Conclusions: Theefficacy and safety results in the Japanese subgroup were generally consistent with the overall results from the PREVAIL trial. Clinical trial information: NCT01212991.
Final results of a phase II study of higher dose docetaxel in androgen independent prostate cancer
Authors: S. D. Glisson, D. A. Laber, J. B. Hargis, R. E. Kosfeld, G. Goldsmith, A. Cervera, R. V. La Rocca
Journal: Journal of Clinical Oncology (2005)

4759 Background: The purpose of this study was to assess the efficacy of single agent docetaxel and gain further knowledge of the toxicity profile of a higher dose than previously evaluated in patients with metastatic and progressive androgen-independent prostate cancer (AIPC). Methods: Docetaxel 100 mg/m2 was administered on day 1 of a three-week cycle. Patients received ciprofloxacin 500 mg orally twice a day from day 4 to 14. The primary endpoint was achievement of a PSA response defined as a decrease in serum PSA more than 50% maintained for 4 weeks. Measurable disease was evaluated by the RECIST criteria. Results: 25 patients with overt and rapid symptomatic deterioration from AIPC were entered into this study. Median age was 68 years and median PSA was 688.4 ng/mL. 9 of 25 patients achieved a reduction in PSA of > 50% and 4 > 80% for an overall PSA response of 52%. 60% of men manifested pain relief. Of the 16 patients with measurable disease, 25% achieved partial response, 44% stable disease, and 31% progressed. Median time to progression was 4.5 months and median survival was 9.3 months. The most common grade 3 or greater toxicities were: 76% neutropenia, 24% anemia, 16% dehydration, 8% fatigue, thrombosis and edema, and 4% allergic reactions, confusion and death. Conclusions: This study demonstrates significant activity of docetaxel in patients with AIPC. The majority of this frail cohort of men achieved pain relief after a relatively high dose of docetaxel. In the study population evaluated, docetaxel toxicity appears unacceptable at this dose and schedule. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Bevacizumab activity in gastric cancer cells with high expression of VEGF.
Authors: Hee Yeon Lee, Jung-Young Shin, Jeong-Oh Kim, Xiang-Hua Zhang, Ji-Eun Oh, Jin Hyoung Kang
Journal: Journal of Clinical Oncology (2012)

64 Background: Metastasis of cancer cells is associated with numerous activating molecules, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-α. Excess VEGF production induces hematogenous metastasis in gastric cancer (GC) cells. To understand the anti-metastatic effect of bevacizumab, an anti-VEGF monoclonal antibody developed for selective inhibition of tumor angiogenesis, we investigated VEGF-induced expression of key adhesion molecules in human umbilical vein endothelial cells (HUVECs) and the inhibitory effect of bevacizumab on the adhesion of GC cells expressing high levels of VEGF. Methods: We measured the soluble VEGF (sVEGF) produced by 7 GC cells by ELISA. We evaluated intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin expression in HUVECs pretreated with SNU-1-conditioned medium (SNU-1 CM) or recombinant VEGF (rhVEGF) at different time points by western blotting. Results: We identified that SNU-1 cells secreted the highest sVEGF concentration in 7 GC cells. After rhVEGF pretreatment, ICAM-1 and E-selectin expression were highest at 4–6 h and 2 h, respectively, but VCAM-1 expression was unchanged. Bevacizumab cotreatment markedly decreased VCAM-1 and E-selectin expression to basal levels, whereas ICAM-1 expression was unaffected. The SNU-1 adherent cell percentage decreased following bevacizumab cotreatment of SNU-1 CM- or rhVEGF-pretreated HUVECs. Investigation of SNU-1-cell invasiveness through activated HUVECs revealed less than 10 invasive adherent cells, whereas no cells were found after bevacizumab cotreatment. Conclusions: Our preclinical data suggests that bevacizumab, might contribute to anti-metastasis by inhibiting SNU-1 cell adhesion to HUVECs by reducing E-selectin and VCAM-1 expression.
Management of chemotherapy-induced remissions in patients with disseminated nonseminomatous germ cell tumors: A review of 98 consecutive patients
Authors: C. R. Nichols, C. J. Moore, B. L. Cho, B. Hayes-Lattin, S. Daneshmand
Journal: Journal of Clinical Oncology (2008)

5037 Background: Management of patients (pts) with nonseminomatous testicular cancer obtaining a chemotherapy-induced complete serologic and radiographic remission (CR) with primary standard BEP chemotherapy is controversial. Approaches vary from the long standing recommendation for observation of such pts to automatic post-chemotherapy retroperitoneal lymph node dissection (RPLND) for all pts (even those in radiographic CR) (Stephenson JCO 25:5597, 2007). Methods: We reviewed 98 consecutive pts (stage IS-III) initially managed with chemotherapy by a single medical oncologist (CN) from 6–98 to 12–07. Pts obtaining CR were observed without surgery. Results: Results are outlined in the table below. 95/98 pts (97%) are alive and currently disease-free with follow-ranging from 2 months to 108 months (median 34 months). There have been three deaths (one germ cell tumor, one second cancer, one gunshot wound). There have been 4 second cancers (2nd primary testis cancer, hairy cell leukemia, early stage renal cell carcinoma, and luminal small bowel adenocarcinoma). There have been no late recurrences of germ cell tumor in this population. With particular emphasis on the behavior of those pts obtaining CR with primary chemotherapy, 4/56 CR pts (7%) experienced a second event. Two pts (both stage III) had either pulmonary or multi-site recurrence of germ cell cancer and two pts (both stage II) had abdominal recurrence of teratoma (14, 34 months). Recurrence appeared in 3/27 (11%) of pts who were NED-teratoma and 2/11 (18%) of pts who were NED-necrosis after primary chemotherapy and surgery. Had uniform application of post-chemotherapy surgery been applied to pts obtaining CR, 56 RPLNDs would have been performed with no patient gaining permanent benefit. Conclusions: Pts obtaining CR after primary standard BEP chemotherapy can be safely observed without routine application of post chemotherapy surgery. Late relapse of cancer and recurrent teratoma are very rare events. Outcome by stage and remission status Stage CR PR mk- NED-Ter NED-Ca NED-nec Relapse by stage IS (n=10) 10 (100%) 0 0 0 0 1/10 (10%) 1 Ter II (n=41) 26 (63%) 1 (2%) 12 (29%) 0 2 (5%) 3/41 (7%) 3 Ter III (n=47) 20 (42%) 3 (6%) 15 (32%) 0 9 (19%) 6/47 (13%) 6 Ca Relapse by remission status 4/56 (7%) 2 Ter/2 Ca 1/4 (25%) 1 Ter 3/27 (11%) 1 Ter/2 Ca 0 2/11 (18%) 2 Ca No significant financial relationships to disclose.