tbuckley/cabot-search huggingface dataset:
A gene expression microarray-based diagnostic test appplied to patients with carcinoma of unknown primary (CUP)
Authors: F. Medeiros, C. P. Kolbert, F. Rakshan Rohakhtar, T. Kane Lindgren, M. J. Wilson, C. T. Rigl, M. P. Goetz, W. D. Henner, K. C. Halling
Journal: Journal of Clinical Oncology (2008)

22123 Background: The workup of tumors presenting as metastatic disease is often laborious and expensive; many malignancies remaining unclassified as to site of origin. A gene expression test has been validated as an identifier of tissue of origin using metastatic tumors in which the primary site is known (Monzon 2007, Dumur 2008). Agreement with pathologist-issued diagnoses was 89.5% (95% CI 86.4 - 92.1%, n = 477). The test is not cleared by the FDA and was not validated in patients with CUP. We sought to determine the diagnostic performance of this test using CUP specimens from the Mayo Clinic tissue bank. Methods: Eleven fresh-frozen tumor biopsies derived from patients with CUP were processed with the Pathwork® Tissue of Origin (TOO) Test (Pathwork Diagnostics, Sunnyvale, CA). The TOO Test uses expression signals from 1,550 probe sets to quantitatively measure the similarity of tumor specimens to 15 tissues of origin. Each patient previously underwent a full clinical and imaging workup; tissue specimens were previously thoroughly evaluated, including extensive immunohistochemistry, with no determination of site of origin. TOO test results were compared with clinical, radiologic and pathologic findings. Results: Of the 11 CUP specimens, 8 (73%) were positive for one of the 15 tissues on the panel and 3 (27%) were indeterminate. In 6 of the positive calls (4 colorectal, 2 ovarian), the result was consistent with the clinicopathologic differential. In 2 cases, the TOO result was unexpected but strongly indicated breast and lung primaries, respectively. On average, 12 tissues per specimen could be eliminated as potential tissue of origin with high probability. Conclusions: The Pathwork Tissue of Origin (TOO) Test successfully indicated a probable origin of metastatic carcinomas in 73% of the specimens tested. We conclude that this test has the potential to aid in the diagnosis of cancer patients presenting with metastatic carcinomas of unknown primary (CUP). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pathwork Diagnostics
The study of efficacy and safety of chemotherapy plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer.
Authors: Nao Takano, Goro Nakayama, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2015)

761 Background: In metastatic colorectal cancer (mCRC), the benefit of the molecular targeted drugs added to chemotherapy has been reported and a combination therapy of capecitabine (CAP) and oxaliplatin (CapeOX) plus bevacizumab (BEV) is an established first-line therapy for mCRC. However, the management of the cumlateve neurotoxicity of oxaliplatin still remains. We evaluated the efficacy and safety of CapeOX plus BEV with oxaliplatin stop and go strategy. Methods: Two prospective clinical trials of previously untreated unresectable mCRC were analyzed. Fifty four patients were treated with CapeOX plus BEV with oxaliplatin stop and go strategy (CCOG-0902). They were treated 4 cycles of CapeOX plus BV therapy followed by maintenance therapy of 8 cycles of Capecitabine plus BV and oxaliplatin reintroduction was scheduled after maintenance therapy or upon tumor progression. On the other group, forty seven patients were treated with mFOLFOX6 plus BEV (CCOG-0801). Progression free survival (PFS), overall survival (OS), response rate (RR), disease control rate (DCR), relative dose intensity (RDI), and frequency of peripheral sensory neuropathy (PSN) were evaluated. Results: Patient characteristics were balanced between the two groups. The median RDI of oxaliplatin in CCOG-0902 group was significantly higher, 92% than in CCOG-0801 group, 80%. RR and DCR were 61.5% and 96.3% respectively, in CCOG-0902 group, compared with 61.7% and 89.4% respectively, in CCOG-0801 group. Median PFS was 13.6 and 30.5 months, respectively, compared with 11.7 and 31.6 months, respectively, in CCOG-0801 group (p=not significant). The frequency of peripheral sensory neuropathy (PSN) was 19.0% (&gt;Grade3: 1.9%) of patients in CCOG-0902 group compared with 72.3% (&gt;grade 3: 17.0%) in CCOG-0801 group. Conclusions: CapeOX plus BV with oxaliplatin stop and go strategy could have same efficacy as continuing oxaliplatin with avoiding PSN. Clinical trial information: UMIN000006478.
Streptozocin-based chemotherapy in patients with advanced pancreatic neuroendocrine tumors.
Authors: Marianne E. Pavel, Lisa-Marie Dilz, Timm Denecke, Ingo Steffen, Vikas Prasad, Ulrich-Frank Pape, Andreas Pascher, Maximilian Heetfeld, Bertram Wiedenmann
Journal: Journal of Clinical Oncology (2014)

295 Background: The role of systemic chemotherapy for advanced pancreatic neuroendocrine tumours (pNETs) is controversially discussed. Objective response rates (RR) with streptozocin(STZ)-based chemotherapy range between 6% and 69%. Novel targeted drugs have recently been approved, however sequence of treatment remains unclear. We aimed to evaluate efficacy of STZ+5-FU chemotherapy in a large pNET cohort. Methods: Clinical data of 95 patients (pts) with advanced pNET who had been treated with STZ+5-FU between Aug 1998 and Sept 2013 were analyzed retrospectively. RR, time to tumour progression (TTP) and overall survival (OS) were assessed. Assessment of RR was judged by tumour board involving an experienced radiologist (TD). Results: Median age at start of chemotherapy was 60 years (range 32-80). 74 pts (77.9%) had non-functional pNETs. In 52 pts (54.7%) STZ+5-FU was 1 st line systemic therapy. 11.6% had G1, 78.9% G2 and 6.3% G3 tumours. Baseline progression was evident in 75.8% of cases. Mean number of therapy cycles was 6 (range 1-18). Treatment was discontinued for toxicity in 15.8% of the cases. Partial response was seen in 43.2% of pts, stable disease in 32.6% and disease progression as best response in 18.9% of cases. Overall TTP was 13.7 months and was independent of prior systemic treatment (1 st line vs. &gt;1 st line, 13.6 vs. 25.3 months, P= 0.54). Functionality had no impact on median TTP. There was no difference between pts with G1 and G2 NET (TTP 21.3 vs. 16.4 months, P=0.78). Median OS was 27.6 months (range 0.8-174 months). In pts with at least two extrapancreatic disease sites (34.7%) median OS was inferior compared to pts with one disease site involvement (37.3 vs. 70.5 months, P=0.02). Conclusions: The combination of STZ and 5FU was associated with a considerable objective response rate in advanced G1/G2 pNETs who had prior disease progression. Efficacy of treatment was not depending on therapy line or grading (G1 vs. G2). Objective response rate is higher than those observed with targeted drugs. This finding along with good tolerability of the treatment strengthens the durable value of this chemotherapy in the era of targeted drugs for the outcome of pts with pNETs.
Relationship of phosphodiesterase type 5 inhibitor to biochemical recurrence after definitive therapy for prostate cancer.
Authors: Michael S. Leapman, Janet E. Cowan, Hao Gia Nguyen, Sima P. Porten, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2016)

119 Background: Phosphodiesterase type 5 inhibitors (PDE5i) are commonly utilized among men receiving definitive treatment for prostate cancer (PCa). Recently, contradictory clinical evidence regarding the association between biochemical recurrence (BCR) and receipt of PDE5i has been reported. We aimed to clarify this question among a multi-center, cohort of men with PCa. Methods: Participants enrolled in Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) at diagnosis and received radical prostatectomy, RP, or radiation therapy, RT (external beam radiation therapy or brachytherapy) without androgen deprivation therapy ≤ 6 months. We examined associations between clinical, Prostate Cancer Index Sexual Function score, SF (0-100 (best)), and pathological characteristics as well as baseline, time-dependent and ever-use of PDE5i (patient or physician reported) with risk of BCR using descriptive analyses, Kaplan-Meier method, and multivariate Cox proportional hazards models. Results: A total of 4,844 men were identified (3,847 RP, 997 RT.) Men received RP at median age 61 years (IQR 56-66), had a mean baseline SF score 62.4 (SD 26.7), were followed for a median of 77 months (IQR 36-117), and 3,089 (80%) were prescribed or reported use of PDE5i post-operatively. Patients treated with RT were older with a median age 69 years (IQR 63-74) and mean baseline SF score 46.6 (SD 29.5), were followed for a median of 91 months (IQR 53-125), and had lower rates of reported PDE5i usage (421 men, 42%). In Cox regression models baseline use (HR = 0.9 (95% CI 0.3-2.4) p = 0.83) and ever-usage (HR = 0.7 (0.5-1.1) p = 0.73) of PDE5i were not independently associated with BCR after RP. Time-dependent use (HR 1.3 (0.6, 2.7) p = 0.45) also was not associated with BCR after RP among men taking PDE5i medications. Baseline (HR = 4.6 (0.6-37.3) p = 0.14) and ever-usage (HR 0.6 (0.3-1.5) p = 0.30) also were not associated with BCR after RT. This study was limited by incomplete data on prescription compliance. Conclusions: PDE5i usage following RP or RT for PCa was not associated with BCR. PDE5i therapy should not be withheld due to concerns that it increases the risk of disease recurrence.
Chemotherapy (CT) use and outcomes in veterans with advanced non small cell lung cancer (NSCLC)
Authors: A. Gajra, J. Husain, N. Newman, L. M. Howard
Journal: Journal of Clinical Oncology (2008)

6625 Background: There are scant data regarding patterns of care for veterans with advanced NSCLC despite a higher incidence of NSCLC in veterans comapred to general population. The veteran population may be unique due to its sociodemographics, comorbidity burden and outlook towards therapy. We carried out a retrospective study to assess CT use among veterans with stage IV NSCLC at the Syracuse VAMC. Methods: After IRB approval patients with stage IV NSCLC were identified from the tumor registry. Medical records were reviewed to obtain: age, sex, smoking history, performance status (PS), dates of diagnosis and death, CT use, radiation and clinical trial participation. A retrospective exploratory analysis was conducted utilizing logistic regression models to determine the statistically significant variables associated with chemotherapy use. Results: A total of 191 patients with stage 4 NSCLC daignosed between 1999 and 2006 were included. The patients were predominantly male and smokers (98% each) with a median age of 68 years. CT was used in 33 % (63/191) of patients. Patients who received CT did not differ in age, gender or smoking status compared to those who did not. Patients treated with CT had: (i) A good PS (ECOG 0,1)- 75% vs. 27% (p =.001) (ii) <5% weight loss - 63% vs 43% (p=.02) and (iii) A lower incidence of adenocarcinoma (34% vs. 59%, p=.01) (iv) Higher serum albumin (p<.01). Major reasons for not receiving CT were poor PS (48 %), physician perception of rapid decline in PS after diagnosis (28%) and patient refusal (10 %). Factors favoring survival included good PS (p<.001) ), weight loss < 5% (.01), and CT use (p<.001). On multivariable analysis CT use retained significance (RR for survival without chemotherapy = 0.42, p< .001). Conclusions: Although it prolongs survival in advanced NSCLC, only a third of elderly veterans received CT in our cohort. Thus, use of current therapies in NSCLC is not applicable to the majority of patients. Age was not a determinant for CT use in this cohort. A significant proportion (27%) did not receive CT despite good PS. There is room for education of providers and patients to alter perceptions. If confirmed in larger series from the VA, such data emphasize the need for health care planning and resource allocation within the VA to address issues specific to the veterans. No significant financial relationships to disclose.
Analysis of the temporal relationship between patient-reported outcomes (PROs) and overall survival (OS) and radiographic progression-free survival (rPFS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts).
Authors: Shana Traina, Tracy Li, Kristen Johnson, Kai Fai Ho, Arturo Molina, David Cella
Journal: Journal of Clinical Oncology (2016)

240 Background: PROs are used to measure therapeutic impact. The relationship between PROs and clinical outcomes is not well described. Methods: COU-AA-301 (301) and COU-AA-302 (302) were phase 3 trials of abiraterone acetate + prednisone (P) vs P in post-docetaxel and chemotherapy-naïve mCRPC pts, respectively. Using Cox regression models, we explored the association between self-reported fatigue, pain, physical well-being (PWB), functional well-being (FWB), and PC-specific (PCS) signs and symptoms, and OS and rPFS over the first 181 days, regardless of treatment, using data from 301 (N = 1195) and, separately, from 302 (N = 1088). Pts in 301 had more advanced disease and were more symptomatic at entry; pts in 302 were asymptomatic/mildly symptomatic. PRO improvements were assessed for 301 and worsening was assessed for 302. Results: In 301, pts with PRO improvements had reduced risk of death and radiographic progression (p &lt; 0.0001) vs pts with worsening or stable PROs (Table). When all PROs were included in a multivariate (MV) model, all except pain intensity were significantly associated with OS; pain intensity, PWB, and FWB improvements were significantly associated with reduced radiographic progression. Pts in 302 with worsening PROs had greater risk of radiographic progression (p ≤ 0.02) vs pts with improved or stable PROs (Table). When all PRO end points were included in an MV model, worsening PWB remained significantly associated with worse rPFS. There were too few events at cutoff to explore the relationship between PROs and OS in 302. Conclusions: These results reinforce the clinical meaningfulness of self-reported symptoms and suggest that PROs can be used in combination with clinical measures in practice. Clinical trial information: NCT00887198; NCT00638690. [Table: see text]
Octreotide LAR use among elderly patients with carcinoid syndrome and survival outcomes: A population-based analysis.
Authors: Chan Shen, Ying Xu, James C. Yao, Ya-Chen T. Shih
Journal: Journal of Clinical Oncology (2013)

322 Background: Octreotide LAR is indicated for the treatment of carcinoid syndrome, diarrhea related to VIPoma, and may delay tumor growth in neuroendocrine tumors (NETs). The pattern of octreotide LAR use in clinical practice and its impact on survival outcomes has not been well-documented. Methods: Using the SEER-Medicare database, we identified NET patients diagnosed between 7/1999 and 12/2007. We excluded those under age 65, enrolled in HMOs, and without continuous Part A and B enrollment within 12 months of diagnosis. Potential indication for octreotide use was defined as ≥ 2 claims for carcinoid syndrome, flushing, diarrhea, or malignant islet cell neoplasm within first year of diagnosis, with the first claim occurring within 6 months of diagnosis. HCPCS codes, J2352 and J2353, were used to identify octreotide LAR treatment. Multivariate logistic regression and Cox proportional hazard survival analyses were performed to ascertain factors associated with octreotide use and evaluate impact of octreotide use on survival; covariates included age, race, region, comorbidity score, urban/rural status, tumor characteristics, neighborhood socioeconomic status and year of diagnosis. Results: Among those with potential indication for octreotide use (carcinoid syndrome and islet cell), 264 (49%) out of 539 distant stage patients, and 83 (10%) out of 850 patients with local regional disease were started on octreotide LAR within 6 months of diagnosis. Multivariate logistic regression showed that patients living in the southern region were less likely to use octreotide. Multivariate proportional hazard model showed that octreotide LAR provided a significant 5-year survival benefit for distant stage patients (HR=.80, p-value=.047); while this survival benefit was not shown for the local/regional stage patients (HR=.97, p-value=.89). Conclusions: This retrospective study suggests a possible survival benefit for use of octreotide LAR in distant stage elderly patients with carcinoid syndrome. Data also suggest that many elderly patients with claims for carcinoid syndrome did not receive octreotide LAR therapy within 6 months of diagnosis. Further studies and improved education are warranted.
Phase II feasibility trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node-positive breast cancer: A trial of the Eastern Cooperative Oncology Group (E2104)
Authors: K. D. Miller, A. O'Neill, E. A. Perez, A. D. Seidman, G. W. Sledge
Journal: Journal of Clinical Oncology (2008)

520 Background: Little is known about the safety of combining bevacizumab and anthracyclines. Therefore, E2104 was a two-arm non-randomized phase II trial designed to evaluate the safety of incorporating bevacizumab into an anthracycline containing adjuvant therapy. Methods: Patients (pts) were sequentially assigned to one of two treatment arms. In addition to dose dense doxorubicin and cyclophosphamide followed by paclitaxel (ddAC>T), all pts received bevacizumab (10 mg/kg q2 wks×26) either initiated concurrently with AC (Arm A: ddBAC>BT>B) or initiated concurrently with paclitaxel (Arm B: ddAC>BT>B). The primary endpoint was the incidence of clinically apparent cardiac dysfunction (CHF). Results: From October 2005 to November 2006, 226 pts were enrolled (Arm A 104, Arm B 122). Median age was 50 (range 27–76). Myelosuppression was common (G3/4 neutropenia 26%) but febrile neutropenia was rare (3%). G3 hypertension/thrombosis/proteinuria/hemorrhage was reported by 11/2/1/<1% of pts. respectively. One pt developed Grade 4 cerebrovascular ischemia. Median follow-up is 14.6 mos. for Arm A and 10.8 mos. for Arm B; to date 52 pts in Arm A and 8 in Arm B have completed planned therapy. Median pre-treatment LVEF was 65% in Arm A and 64% in Arm B. Clinical CHF was reported in 2 pts in Arm A after 4 and 6 cycles; four pts had asymptomatic declines in LVEF to <40% after 4 (n=1) and 16 cycles (n=3). Two pts in Arm B reported clinical CHF due to diastolic dysfunction (both associated with a decline in LVEF to 40–50%) after 4 and 9 cycles; one pt had asymptomatic decline in LVEF to <40% after 8 cycles. Conclusions: Preliminary data suggests incorporation of bevacizumab into anthracycline-containing adjuvant therapy is feasible. Ongoing cardiac monitoring is required to define the true impact of bevacizumab on cardiac function. Arm A Arm B Baseline and post Cycle 4 LVEF (C5D1) available 93 106 Median post Cycle 4 LVEF 63% 61% Pts with post Cycle 4 LVEF decline > 10% 13 (14%) 7 (7%) Pts with post Cycle 4 drop >10% & LVEF < LLN 2 2 Baseline and post Cycle 8 LVEF (C9D1) available 81 88 Median post Cycle 8 LVEF 62% 62% Pts with post Cycle 8 LVEF decline > 10% 9 (11%) 8 (9%) Pts with post Cycle 8 drop >10% & LVEF < LLN 0 1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Roche Roche Genentech, Roche
Dihydro pyrimidine dehydrogenase deficiency in patients treated with capecitabine-based regimens: A retrospective tertiary care centre experience.
Authors: Arvind Sahu, Vikas S. Ostwal, Anant Ramaswamy
Journal: Journal of Clinical Oncology (2016)

712 Background: Capecitabine is an integral part of treatment of gastrointestinal cancers. Dihydropyrimidine dehydrogenase (DPD) enzyme is rate limiting in the metabolism of capecitabine, deficiency of which leads to myelsuppression, mucositis, diarrhea, hand foot syndrome (HFS) and rarely, death. Data regarding the toxicity of capecitabine in patients with DPD deficiency in the Indian context is scarce. Methods: 506 patients were treated with capecitabine containing regimens with a dose range of 1250 mg/m2/day to 2000 mg/m2/day during the period from June 2013 to May 2015 in the Gastrointestinal Medical Oncology Unit of our institution. Patients with Grade 3/4 toxicities requiring in-patient care (life threatening complications) were planned for DPD activity testing by Peripheral Blood PCR sequencing. Results: 27 patients developed Gr 3/4 toxicities during cycle 1 of capecitabine. It included mucositis in 22 (81.5 %), diarrhea in 25 (92.6%), HFS in 10 (37%) and myelosuppression in 4 (14.8%). 19 were found to be DPD deficient with 5 patients negative for DPD mutation. 3 patients did not do the DPD analysis as advised. Homozygous mutations were seen in 9 (33.3%) and heterozygous mutations in 10 (27%) of patients. More than one mutation was seen in 10 patients (37%). The relative frequencies of mutation were Exon 14 (44.4%), Exon 2 (25.9%), Exon 13 (25.9%), Exon 6 (11.1%) and Exon 18 (7.4 %). Post Cycle 1 of capecitabine, the drug was stopped in 5 patients (18.5%), regimen changed in 2 (7.4%) and dose reduction by 50% of the drug was done in the remaining patients. Despite dose reduction and change in therapy during Cycle 2, patients still had Grade 3/4 toxicities including mucositis in 7(25.9%), diarrhoea in 10 (37%), HFS in 7 (25.9 %) and myelosuppression in 6 (22%) of patients. Conclusions: Capecitabine can also lead to severe toxicities in DPD-deficient patients. Dose reduction of capecitabine in DPD deficient patients may not completely ameliorate the future risk of life – threatening complications. Screening for DPD deficiency prior to administration of capecitabine in toxicity prone nutritionally deficient Indian patients should be further evaluated based on this data.
Comprehensive evaluation of the clinical utility of transperineal template guided mapping biopsy of prostate in the era of magnetic resonance imaging.
Authors: Arjun Sivaraman, Rafael Sanchez-Salas, Eric Barret, Marc Galiano, Francois Rozet, Dominic Prapotnich, Nathalia Cathala, Annick Mombet, Facundo Uriburu, Arie Carneiro, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2015)

55 Background: To evaluate the clinical utility of Transperineal Template guided Mapping Biopsy (TTMB) after the routine use of Magnetic Resonance Imaging (MRI) for prostate cancer in our institution. Methods: We retrospectively analyzed 208 TTMB performed at our institution from April 2013 - August 2014. Anterior cancer defined as ≥ 80% of the positive cores anterior to urethra. Clinically significant cancer detection verified at various thresholds of Maximum Cancer Core Length (MCL) – 2mm / 3mm / 4mm / 6mm ± Gleason score (GS) ≥ 3+4. We analyzed TTMB for the indications, cancer detection and correlation with TRUS, MRI and Radical Prostatectomy (RP) specimens. Results: The indications and cancer detection rates of TTMB are in the table. All the patients had MRI before TTMB and 87.7% had it prior to the initial TRUS and all target biopsies were by cognitive registration. Multivariate analysis showed higher number of TTMB cores and prior negative TRUS to predict detection of clinically significant anterior tumor. The laterality of cancer in TTMB correlated with TRUS, MRI and Radical Prostatectomy (RP) in 67.2%, 75.3% and 87.6% respectively. The Gleason upgrade from TRUS to TTMB was 19.2% and TTMB to RP was 14.8%.Clavien-Dindo grade 1 and 2 complication was noted in 40.2% and 7% patients respectively. Conclusions: Even with the routine of MRI prior to TRUS biopsy, TTMB had clinical utility and was very effective in detecting clinically significant cancers in specific clinical situations. [Table: see text]