tbuckley/cabot-search huggingface dataset:
The impact of PBRM1 and BAP1 expression on outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT).
Authors: Andre Poisl Fay, Guillermo de Velasco, Kathryn P. Gray, Thai Huu Ho, Jiaxi Song, Payal Kapur, Laurence Albiges, David F. McDermott, Daniel Yick Chin Heng, James Brugarolas, Toni K. Choueiri, Sabina Signoretti
Journal: Journal of Clinical Oncology (2016)

616 Background: Polybromo-1 (PBRM1) and BRCA1 associated protein-1 (BAP1) are genes commonly mutated in clear cell RCC (ccRCC) and have been associated with clinical outcome. This work aims to evaluate the impact of PBRM1 and BAP1 expression by IHC in mRCC patients treated with VEGF-TT. Methods: PBRM1 and BAP1 expression was evaluated by IHC in a TMA including 146 mRCC patients. PBRM1 and BAP1 IHC scores were dichotomized as a binary variable: negative (-) or positive (+) (weak positivity was excluded). The associations of PBRM1 or BAP1 expression with baseline clinico-pathological characteristics were evaluated, as well as with overall survival (OS) and time to treatment failure (TTF) usingCox proportional hazards models. Results: Out of 146 patients, 116 and 109 samples had available results for PBRM1 and BAP1 staining, respectively. Overall, 90% (n = 131) patients had ccRCC. 70/116 samples (60%) were PBRM1- and 26/109 patients (24%) were BAP1-. Only 12% (n = 13) of patients had simultaneous negative PBRM1 and BAP1. While there was no association between PBRM1 expression status and clinical factors, BAP1- samples were associated with poor IMDC prognostic risk score (p = 0.004) and higher Fuhrman grade (p = 0.012). PBRM1+ patients showed a trend towards an increased risk of death and a shorter TTF compared to PBRM1- patients (OS: HR = 1.38, 95%CI: 0.92-2.07, p = 0.1; TTF: HR = 1.39, 95%CI: 0.94-2.06, p = 0.1). BAP1 expression was not independently associated with OS or TTF. Conclusions: Loss of PBRM1, but not BAP1 expression showed a trend towards longer TTF and OS in mRCC patients treated with VEGF-TT.
The ratio of major and minor axis by EUS as a possible predictive marker for the diagnosis of submucosal invasive gastric cancer.
Authors: Jae Jin Hwang, Young Soo Park, Dong Ho Lee, Hyun chae Jung
Journal: Journal of Clinical Oncology (2016)

9 Background: The aim of this study was to evaluate the efficacy of the ratio of major and minor axis by endoscopic ultrasonography (EUS) as a possible predictive marker for the diagnosis of submucosal invasive gastric cancer. Methods: Between March 2014 and December 2014, the medical records of 51 patients with unclear distinction between mucosal and submucosal gastric cancer were retrospectively reviewed. Patient and tumor characteristics, accuracy rate and factors associated with correct diagnosis of submucosal invasive tumor in Ratio for gastric cancer were analyzed. Results: The mean age was 62.0 ± 12.6 (range, 35-79 years) and the male to female ratio was 1:0.45. The mean tumor size was 25.8 ± 14.7 mm. The overall accuracy was 60.7% (31/51) using the EUS and 82.3% (42/51) using the EUS ratio index (p = 0.045). The sensitivity, specificity, positive predictive value and negative predictive value to submucosal gastric cancer were 68.1, 55.1, 53.5, 65.9% using the EUS and 81.8,82.7,78.2,85.7% using the EUS ratio index, respectively. In the multivariate analysis, differentiated (Odds ratio [OR]: 1.42, 95% confidence interval [CI]: 0.95-1.89), no ulceration (OR: 1.96, 95% CI: 1.49-2.43), and deep submucosal invasion ( &gt; 500 μm, OR: 2.77, 95% CI: 2.16-3.34) were independent factors, associated with correct diagnosis of submucosal invasive tumor in Ratio for gastric cancer (p &lt; 0.05) Conclusions: The ratio of major and minor axis by endoscopic ultrasonography (EUS ratio index) might be a possible predictive marker for the diagnosis of submucosal invasive gastric cancer.
Referral trends for reproductive-age patients with breast cancer to a reproductive endocrinology clinic for fertility preservation counseling between 2004 and 2012.
Authors: Jonathan David Kort, Kira Seiger, Solomon Henry, Lynn Westphal
Journal: Journal of Clinical Oncology (2013)

129 Background: As of October 2012, both embryo and oocyte cryopreservation are considered non-experimental fertility preservation (FP) options for cancer patients facing potentially gonadotoxic therapy. This study aims to assess the historical referral frequency of reproductive aged breast cancer patients from a major cancer center to an associated reproductive endocrinology and infertility (REI) clinic for counseling regarding FP and also assess how frequently these patients underwent FP after referral. Methods: Using the Stanford Cancer Center Research Database in conjunction with our EMR, a query was made for patients of reproductive age (13-45) who were seen at the Stanford Cancer Center for a new breast cancer diagnosis between 2004 and 2012. These patients’ records were then searched for referral encounters in the REI department. Those who were seen by REI were assessed for having undergone FP via embryo or oocyte cryopreservation prior to starting chemotherapy. Results: 420 women, ages 20 to 45, were seen at our cancer center for a new diagnosis of breast cancer between 2004 and 2012. Sixty (14.3%) of these patients, ages 20 to 42 at diagnosis, were referred to the REI department for FP counseling. Patients who were referred for FP counseling were 5.1 years younger at diagnosis than those who were not (p&lt;.005). Of those referred, 33.3% underwent FP with embryo (77%) or oocyte cryopreservation (23%) under an experimental protocol. Among breast cancer patients ≤35 years old, 35% were referred to our REI department for FP counseling and 53.5% of those referred underwent FP. Conclusions: Despite advances in FP technology, the majority of reproductive aged breast cancer patients are still not referred for FP counseling by a reproductive endocrinologist. This trend was also seen among patients younger than 35—a subgroup who is more likely to undergo and benefit most from FP. This study does not reflect patients who decline this opportunity or seek FP elsewhere, however additional study and outreach is needed to improve referral rates, which are now a measure of the Quality Oncology Practice Initiative (QOPI).
Treatment of locally advanced pancreatic cancer with concurrent chemoradiotherapy with gemcitabine: Results from 24 patients treated from 2003-2009.
Authors: K. Yamada, T. Oda, S. Hashimoto, Y. Ohara, A. Kobayashi, K. Fukunaga, S. Murata, R. Sasaki, N. Ohkohchi
Journal: Journal of Clinical Oncology (2010)

e14684 Background: Local control of locally advanced pancreatic cancer with radiotherapy plus gemcitabine has demonstrated overall survival benefit without apparent long term adverse impact on QOL when compared with gemcitabine alone. We evaluated safety and efficacy of concurrent chemoradiotherapy with gemcitabine in patients with LAPC. Methods: Patients with unresectable nonmetastatic invasive ductal pancreatic cancer with ECOG performance status of 0-1 were eligible. Surgical staging was not required. Gemcitabine was administered at 250 mg/m2 twice daily every day with 5 days per week radiotherapy (1.8 Gy fractions) over the 5 weeks followed by 6 cycles and more of gemcitabine alone (1,000 mg/m2 weekly x 3 every 4 wks). Results: From April, 2003 to January 2009, 24 patients were enrolled, 24 (100%) were patients completed concurrent chemoradiotherapy. Male:Female- 14:10 with a median age of 67 (range: 48-82). Tumor response was 0%. The confirmed tumor marker response rate(less than 50% before the treatment) is 92% (22/24). Median time to progression 6.4 mos (95% CI [2.0, 16.6]), and median survival time 11.4 mos (95% CI [6.0, 23.3]) were observed. Twelve (50%) and 7 (29%) patients experienced at least one grade 3+ or grade 4+ adverse event, respectively. The most common grade 3-4 toxicities were neutropenia (33%), anemia (17%), anorexia (25%), nausea (25%), vomiting (25%). Conclusions: concurrent chemoradiotherapy combined with gemcitabine is a well tolerated and effective treatment for patients with locally advanced pancreatic cancer. No significant financial relationships to disclose.
Effect of cathepsin k inhibition on suppression of bone resorption in women with breast cancer and established bone metastases in a 4-week, double-blind, randomized controlled trial
Authors: A. B. Jensen, N. Olmeo, C. Wynne, G. Ramirez, A. Lebrecht, A. Mehta, W. He, Y. Song, Y. Berd, A. Lombardi
Journal: Journal of Clinical Oncology (2008)

1023 Background: In breast cancer patients with metastatic bone disease (MBD), osteolysis releases factors that sustain tumor cell survival and proliferation. Cathepsin (Cat) K inhibition suppresses osteolysis in preclinical models of MBD. The current study assessed the safety and efficacy of odanacatib, a selective Cat K inhibitor, in reducing markers of bone remodeling in women with breast cancer and MBD. Methods: This double-blind study randomized women with breast cancer and MBD to oral odanacatib 5 mg daily for 4 weeks or IV zoledronic acid (ZA) 4 mg given once at study initiation. Bone remodeling was assessed by measuring urinary N-telopeptide of type I collagen corrected for creatinine (uNTx; primary objective, pmol BCE/μmol creatinine); urinary deoxypyridinoline corrected for creatinine (uDPD, pmol/μmol creatinine), and bone formation (serum bone-specific alkaline phosphatase [sBSAP, ng/mL]). Inhibition of Cat K activity was determined by serum crosslinked C-terminal peptide of type I collagen (s1CTP, μg/L). Adverse events (AE) were monitored throughout the 4-week study and up to 14 days after last dose. Results: 43 patients (mean age 60 yrs) received odanacatib (n=29) or ZA (n=14); 40 patients completed 4 weeks. 12 (41%) and 17 (59%) patients on odanacatib and 6 (43%) and 7 (50%) patients on ZA received chemotherapy or hormone therapy, respectively. Results for markers of bone remodeling and Cat K activity are tabulated (Table). The most common AEs were nausea, vomiting, headache, and bone pain, which were generally not attributed to study drug. Conclusions: In women with breast cancer and MBD, the Cat K inhibitor odanacatib suppressed markers of bone resorption after 4 weeks of treatment. Mean uNTx and uDPD were decreased in both treatment groups. The increase in s1CTP suggests specific inhibition of Cat K. In this study, odanacatib was generally safe and well tolerated. Changes from Baseline at Week 4 in Biochemical Markers of Bone Resorption Marker Odanacatib 5 mg (once daily) Zoledronic Acid 4 mg (single dose) Baseline Wk 4 % Change 95% CI Baseline Wk 4 % Change 95% CI uNTx 140 48 -77 -82, -71 175 61 -73 -80, -62 uDPD 18 13 -30 -43, -15 25 15 -52 -64, -36 sBSAP 27 25 -9 -17, -2 36 32 -2 -13, +9 s-1CTP 10 20 +93 +70, +119 10 10 0 -16, +19 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck & Co., Inc Merck & Co., Inc
Evaluating women with ovarian cancer for <i>BRCA 1/2</i>: Missed opportunities
Authors: L. Meyer, S. N. Westin, R. A. Lacour, D. L. Urbauer, K. M. Schmeler, M. S. Daniels, C. C. Sun, D. M. Gershenson, K. H. Lu
Journal: Journal of Clinical Oncology (2008)

5532 Background: Genetic testing for a BRCA 1/2 mutation is most efficient and effective when first performed on a cancer patient. Despite its availability, we hypothesized that physicians caring for cancer patients have not adopted hereditary cancer risk assessment into routine oncology practice. As a test case, we examined the rate of genetic counseling referrals for women with ovarian cancer who were at substantial risk for having a germline BRCA mutation. Methods: Family history information was collected from the initial history and physical (H&P) and personal history database of all new patients with ovarian cancer at a tertiary care center in 2000 and 2006. Using the Society of Gynecologic Oncology (SGO) guidelines for genetic counseling referral, we identified patients at substantial (20–25%) risk of a BRCA 1/2 mutation. All subsequent visits were reviewed for referral to genetic counseling. Descriptive, Fisher’s Exact and Kappa statistics were utilized for statistical analysis. Results: 459 women in 2000 and 407 women in 2006 with epithelial ovarian cancer were seen as new patients. Family history was dictated in the initial H&P for 92.8% of patients in 2000 and 97.3% in 2006. Agreement between the personal history database and dictated family history was high (κ=0.92, 95% CI=0.88–0.97). In 2000, 17 of 98 (17.4%) patients at substantial (20–25%) risk of a BRCA mutation were referred. In 2006, 34 of 74 (46%) of patients at substantial (20–25%) risk were referred (p=0.0001). New patients undergoing primary therapy were more often referred for genetic counseling than new patients seen with recurrent disease or patients seen as a second opinion (p=0.0035). Conclusions: Although most patients had an accurate family history dictated, the interpretation of risk for BRCA1/2 mutations and subsequent referral to genetic counseling was poor in 2000. While the improvement in 2006 corresponded to the addition of genetic counseling services in our clinic, still over 50% of high risk patients were not referred. Given the benefit to the family and the possible direct benefit to the patient through new targeted therapeutics, greater attention to the process of hereditary cancer risk assessment and identification of women with BRCA 1/2 mutations is essential. No significant financial relationships to disclose.
Very Poor Long-Term Survival, Also in Contemporary Studies, of Patients with AML Who Relapse after Achieving a First Complete Remission: The ECOG-ACRIN Cancer Research Group Experience
Authors: Chezi Ganzel, Larry D. Cripe, Zhouxin Sun, Hugo F. Fernandez, Peter A Cassileth, Dan Douer, Jacob M. Rowe, Elisabeth Paietta, Michael O'Connell, Peter H Wiernik, John M. Bennett, Mark R Litzow, Selina Luger, Hillard M. Lazarus, Martin S. Tallman
Journal: Blood (2015)
Cytoreductive radical prostatectomy (CRP) in patients with prostate cancer (PCA) and low-volume osseous metastases.
Authors: Axel Heidenreich, Andrea K. Thissen, Charlotte Piper, David J. K. P. Pfister, Daniel Porres
Journal: Journal of Clinical Oncology (2014)

272 Background: Androgen deprivation (ADT) represents the standard treatment in men with prostate cancer (PCA) and osseous metastases. Unlike therapeutic approaches in other solid tumors, RP is usually ignored due to the common view that the biology of the disease is attributed to preexisting metastases. Recently, it has been shown that potentially lethal cancers persist even after neoadjuvant ADT and chemotherapy. We explored the outcome of patients with PCA and low volume skeletal metastases who were subjected to ADT and cytoreductive radical prostatectomy (CRP). Methods: Eighteen patients with biopsy proven, completely resectable PCA, minimal osseous metastases (equal to or less than three hot spots on bone scan), absence of visceral or extensive lymph node metastases were included in the pilot study. All patients (pts) underwent neoadjuvant ADT with luteinizing hormone-releasing hormone (LHRH) analogues for 6 months. If the PSA serum level decreased to less than 0.4 ng/ml and osseous lesions disappeared on control scan, pts were considered suitable for extended RP followed by 2 years adjuvant ADT. Results: Mean age was 61 (42 to 69), the mean PSA was 96.3 (72 to 139) ng/ml and 0.29 (0 to 0.39) ng/ml at recruitment and at 6 months, respectively. Mean number of bone lesions was 1.9 (1 to 3) and all lesions disappeared after 6 months of ADT. Pathohistology revealed pT2c in 4 (22.2%), pT3a and pT3b in 3 (16.7%) and 11 (61.11%) pts, respectively. Seven (38.9%) pts and three (16.7%) pts had lymph node metastases or positive surgical margins (PSM). PSM were treated with adjuvant radiation therapy ad 66.6Gy. No Clavien grade 3 to 5 complications occurred. The mean follow-up is 29 (3 to 52) months, three (16.7%) pts relapsed. The remainder is without evidence of disease. Conclusions: CRP is feasible in well selected men with low volume osseous metastases who respond well to neoadjuvant ADT. These men have a life expectancy of around 7 years and CRP reduces the risk of locally recurrent PCA and local complications. CRP might be a new treatment option in the multimodality management of PCA and minimal metastatic disease.
Recombinant adenovirus-p53 (rAd-p53) in combination with radiotherapy for treating cervical cancer.
Authors: S. Zhang
Journal: Journal of Clinical Oncology (2011)

5096 Background: To evaluate efficacy and safety of rAd-p53 in combination with radiotherapy in treatment of unresectable cervical cancer. Methods: Patients with primary unresectable squamous cell carcinoma of the cervix of FIGO late-stage IIband IIIb were intratumorally injected with rAd-p53 of 1 ′ 1012 virus particles (vp) once a week for 6 weeks in combination with concurrently pelvic RT plus brachytherapy at point A at a total dose of 73.9 SD 3.8 Gy. Results: From March 2002 to May 2010, 31 patients, 14 patients in IIb and 17 patients in IIIb of locally advanced squamous cell carcinoma of the cervix, were enrolled into this phase II study. All patients experienced complete response (CR) immediately after treatment. No local and pelvic recurrence was found during follow-up period. Distant metastasis occurred in 2 cased (6.5%). The median survival time was 96 months (95% CI, 79 to 112 months). Five-years of survival rate was 85.7%, which is 30.0% higher than 55.3% of survival rate from a study including 140,000 cases with stage I-IV of cervical cancer treated using radiotherapy alone. No dose-limiting toxicity or serious adverse events appeared, except for transient fever after rAd-p53 administration. Conclusions: RAd-p53 in combination with radiotherapy was safe and effective in treatment of unresectable cervical cancer.
Creutzfeldt-Jakob Disease Mimicking Alzheimer Disease and Dementia With Lewy Bodies—Findings of FDG PET With 3-Dimensional Stereotactic Surface Projection
Authors: Nobuhiko Miyazawa
Journal: Clinical Nuclear Medicine (2017)

A 78-year-old man received a diagnosis of sporadic Creutzfeldt-Jakob disease based on symptoms and findings of MRI, FDG PET, and cerebrospinal fluid markers. PET with 3-dimensional stereotactic surface projection (3D-SSP) showed that the distribution of hypometabolism mimicked that of Alzheimer disease. A 68-year-old woman was treated under a diagnosis of convulsion. Findings of MRI, PET, familial history, and cerebrospinal fluid markers revealed familial Creutzfeldt-Jakob disease. FDG PET with 3D-SSP disclosed that the hypometabolic pattern mimicked that of dementia with Lewy bodies. FDG PET with 3D-SSP can demonstrate similar patterns in various neurodegenerative disorders.
How are colorectal cancer (CRC) patients treated following cancer recurrence during follow-up?
Authors: Katherine Van Loon, Chung-Yuan Hu, Amanda Cuddy, Tanios S. Bekaii-Saab, Al Bowen Benson, Michael J. Hall, Lily L. Lai, Steven J. Nurkin, John Michael Skibber, Martin R. Weiser, Deborah Schrag, George J. Chang
Journal: Journal of Clinical Oncology (2016)

645 Background: A major goal of surveillance following curative resection for CRC is identification of treatable recurrence. However, there is a paucity of data regarding optimal frequency or duration of surveillance or potential for salvage therapy following detection of recurrence. The aim of this study was to examine treatment patterns following recurrence of CRC. Methods: Patients ≥ 18 years who presented to 8 participating NCCN institutions between 2005-2012 with resected stage I, II, or III CRC were identified. Time to recurrence was determined by the Kaplan-Meier method and descriptive statistics were used to report treatments following recurrence. Results: Of 5653 patients who underwent resection for locoregional CRC (2984 colon, 2669 rectal and rectosigmoid), median age was 60 [IQR: 50-70]. 53.5% were male. With a median follow-up time after diagnosis of 23.5 months (11.0-45.2), 641 recurrences (6.9% local; 93.1% distant) were identified. Median time to local recurrence was 16.1 months [IQR: 12.5-27.3]. Median time to distant recurrence was 15.6 months [IQR: 11.2-23.9]. Among 325 recurrences of a colon primary, 18 (5.5%) were local and 307 (94.5%) were distant; liver and lung were most common sites (30.8% and 13.9%, respectively). Among 316 recurrences of a rectal primary, 26 (8.2%) were local and 290 (91.8%) were distant; lung and liver were most common sites (35.8% and 21.8%, respectively). Of 597 patients who developed a metastatic recurrence, 227 (38.0%) underwent metastectomy (79 liver and 76 lung resections) and 26 (4.3%) underwent ablation. 414 (64.6%) received chemotherapy and 64 (10%) received radiation. 133 (20.7%) died without treatment &lt; 1 year after recurrence. Of 641 patients,113 (17.6%) had synchronous sites of recurrence and 152 (23.7%) developed recurrence at a second site within 12 months. Conclusions: A high rate of metastectomy was observed following detection of recurrence within the NCCN hospitals. However, a significant proportion of patients had a second site of recurrence &lt; 12 months after initial recurrence. Further inquiry into optimal surveillance and management of recurrence for patients following curative resection of CRC is needed. (Support: U10CA180821, CE-1304-6543).
Phase I study of concurrent weekly docetaxel (Tax) and repeated <sup>153</sup>Sm-lexidronam (Sam) in androgen-independent prostate cancer (AIPC)
Authors: S. Tu, D. Jones, P. Mathew, C. J. Logothetis
Journal: Journal of Clinical Oncology (2008)

5132 Background: Recent studies have shown that Tax based chemotherapy (CT) prolongs survival in Pts with AIPC. Other studies have shown anti-tumor activity and enhanced survival when a bone-targeted radionuclide was combined with CT. This study evaluated the safety of 2 cycles of Sam administered concurrently with a weekly regimen of Tax. Methods: Pts with progressive AIPC and ≥3 bone metastases were treated in cohorts (CH) of 3–6. Pts with >2 prior cytotoxic CT regimens or >2 radiation treatments (RT) to bone were excluded. CHs were defined by dose escalation of Tax: 25, 30 and 35 mg/m2with Sam dose of 1 mCi/kg/cycle. Sam is given on day 1 and Tax on days 1,8 and 15 of each 28 day cycle. Pt must have ANC > 1,000 and PLT > 70,000 to receive Tax and PLT > 100,000 and ANC >1,500 to receive 2nd dose of Sam. Delay of >7 days for Tax or 28 days for Sam for count recovery was considered dose limiting toxicity (DLT). Results: 18 patients completed, 6 in each CH. Baseline age: 71 (49–84) yrs, PSA: 61 (7–1,348) ng/mL, alkaline phosphatase: 148 (57–1045) IU/L. 16 pts had at least one prior course of CT, 11 had prior RT and 13 had more than 10 bone metastases. 2 pts in CH 1 withdrew due to disease progression prior to 2nd Sam dose. 1 pt each in CHs 2 and 3 had delay of hematologic recovery (1 PLT and 1 ANC) precluding a 2nd Sam dose. Both patients recovered sufficiantly to continue Tax alone. Median time between Sam doses was 35 days in each CH. Median nadir levels of PLT and ANC (x 1,000/mm3) are shown in the Table. One pt (CH 1, cycle 1) experienced grade 3 PLT toxicity and 2 pts (CH 3, cycle 1) grade 3 ANC toxicity; no grade 4 PLT or ANC, and no grade ≥3 non-hematologic toxicities related to treatment were reported. Conclusions: Administration of weekly Tax in combination with 2 cycles of Sam did not result in DLT. Hematologic toxicity was mild, reversible and did not limit further CT. Nadir levels of PLT and ANC following combination cycle 2 were similar to those following the first. ANC PLT Cycle 1 Cycle 2 Cycle 1 Cycle 2 CH 1 2.0 2.1 104 170 CH 2 1.6 1.6 114 109 CH 3 2.3 1.9 125 148 No significant financial relationships to disclose.