tbuckley/cabot-search huggingface dataset:
Effect of targeted therapy on rapid progression and early death in renal cell carcinoma.
Authors: Shenhong Wu
Journal: Journal of Clinical Oncology (2013)

389 Background: Several targeted therapeutic agents have been approved for the treatment of advanced renal cell carcinoma (RCC) due to their efficacy in overall patient population. However, their effects have not been defined in patients with rapid progressive cancer, which is characterized by progression within three months and associated with poor prognosis. Therefore, we conducted a systematic review and meta-analysis of published randomized controlled clinical trials (RCTs) to assess the effect of targeted therapy on rapid progressive RCC. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October, 2012, were searched to identify relevant studies. Rapid progression was defined as progressive disease or death at three months after the initiation of clinical trial. Eligible studies included prospective RCTs in which a targeted therapy was compared to a control in RCC patients. Summary incidence of rapid progression or death, relative risk (RR), and 95% confidence interval (CI) were calculated based on the heterogeneity of included studies. Results: A total of 4,628 patients (targeted therapy: 2,461, control: 2,167) with RCC from 10 RCTs were included for analysis. The overall incidence of cancer rapid progression with the targeted therapy was 23.6% (95% CI: 19.2-28.6%). When compared to controls including interferon or placebo, the targeted therapy significantly reduced the overall risk of rapid progression (23.6% vs. 54.5%; overall RR=0.46, 95% CI: 0.38-0.54, p&lt;0.001; versus IFN: RR=0.55, versus placebo: RR=0.38). The effect varied significantly among different agents (p&lt;0.001), with the highest reduction seen in patients treated with pazopanib (RR=0.27; 95% CI: 0.21-0.35). There was no significant difference between mTOR and VEGF inhibitors (p=0.25). In addition, the targeted therapy significantly reduced the risk of mortality at 3 months (5.5% vs. 10.0%; RR=0.58, 95% CI: 0.41-0.81; p=0.002). Conclusions: The targeted therapeutic agents may significantly reduce the risk of rapid progression and early death in patients with renal cell cancer.
Identifying dehydration risk in head and neck cancer patients undergoing radiation therapy using remote, sensor-based monitoring: A randomized controlled trial.
Authors: Susan K. Peterson, Eileen H. Shinn, Adam S. Garden, Kevin Patrick, Sanjay Shete, Chan Shen, Stephanie L. Martch, Emilia Farcas, Kai Lin, Frederic Raab, Nancy Asomaning, Israel Christie, Viswanath Nandigam, Tony Chen, Yan Yan, Beth Michelle Beadle
Journal: Journal of Clinical Oncology (2016)

152 Background: Early identification and mitigation of cancer therapy-induced complications can improve quality of life and reduce complications and health care costs. We are evaluating the efficacy of a system, called CYCORE (CYberinfrastructure for Comparative effectiveness Research), to systematically and accurately collect daily weight, blood pressure, pulse and symptom data from head and neck cancer (HNC) survivors during their 6 to 7-week radiation treatment (RT) regimen using home-based biometric and other sensors integrated with a cyber-physical system. Aims include: 1) evaluate CYCORE’s efficacy in reducing hospitalization and emergency room visits related to dehydration; and, 2) evaluate related impact on costs related to treating dehydration. Methods: Remote, sensor-based monitoring via CYCORE identifies HNC survivors at increased risk for dehydration (i.e., reduced blood pressure and weight, increased pulse, and patient-reported outcomes (PROs) including decreased food and fluid intake). Upon initation of RT, HNC survivors are randomized to either: 1) standard care plus use of the CYCORE system, wherein biometric sensor data and PROs (e.g., pain, nausea, medications, food/fluid intake) are collected ; or, 2) standard care. Outcomes include hospital and emergency room admissions, and related costs. Results: To date, 113 survivors are enrolled (88.9% recruitment and 90.3% retention rates). Those randomized to CYCORE take daily home readings of weight, blood pressure and pulse via Bluetooth-enabled devices, and complete daily PRO assessments on a mobile application. Survivors’ data are available for viewing and clinical decision-making via a Web-based interface by their physicians and other providers. Previously, 59% of HNC survivors on RT showed physiologic signs of dehydration while using the CYCORE system. Worse ratings of nausea and vomiting predicted dehydration risk. Conclusions: CYCORE may serve as one model for integrating mobile and sensor technologies during critical periods of cancer care that occur outside of the clinic setting, and may improve management of treatment side effects, quality of life, and greater satisfaction with care. Clinical trial information: NCT02253238.
Mature results from Hoosier Oncology Group GU04-75 phase II trial of cisplatin (C), gemcitabine (G), and bevacizumab (B) as first-line chemotherapy for metastatic urothelial carcinoma (UC).
Authors: N. M. Hahn, W. M. Stadler, R. Zon, D. M. Waterhouse, J. Picus, S. R. Nattam, C. S. Johnson, S. M. Perkins, M. J. Waddell, C. Sweeney
Journal: Journal of Clinical Oncology (2010)

4541 Background: Initial results of CGB therapy in metastatic UC patients demonstrated encouraging response and overall survival results with concerning rates of toxicity (Hahn et al ASCO 2008, abst 5018). This summary provides updated results of CGB efficacy and toxicity with mature patient followup. Methods: Metastatic or unresectable chemonaive UC patients (pts) received C 70 mg/m2 iv d1, G 1000- 1250 mg/m2 iv d1, 8, and B 15 mg/kg iv d1 on a q21d cycle as previously described. The primary endpoint was progression-free survival (PFS). Results: 43pts were enrolled and treated. Patient demographics have previously been described. Grade 3-4 hematologic toxicity included: neutropenia 35%, thrombocytopenia 12%, anemia 12%, and neutropenic fever 2%. Grade 3-4 non-hematologic toxicity included: DVT/PE 21%, hemorrhage 7%, hypertension 5%, and proteinuria 2%. 3 treatment related deaths (1 CNS hemorrhage, 1 sudden cardiac death, 1 aortic dissection) were observed. Only 2 DVT/PE events were observed following protocol amended G dose reduction. Best RECIST response was: complete response 9 pts (21%, 95% CI 10-36%), partial response 22 pts (51%, 95% CI 36-67%); with overall response rate of 72% (95% CI 56-85%). Stable disease lasting at least 12 weeks was observed in 7 pts (16%, 95% CI 7-31%) and progressive disease in 4 pts (10%, 95% CI 3- 22%). With a median followup of 27.2 months (Range 1.6-40.9), median PFS was 8.2 months (95% CI 7.3 – 10.5) with a median overall survival (OS) of 20.4 months (95% CI 14.7 – 23.4). Unplanned multivariable analysis revealed significant associations between improved OS and less than two metastatic sites (p<0.01), female gender (p<0.01), G dose 1250 mg/m2 (p=0.03), and lower body mass index (BMI) (p=0.02). Significant univariate associations between higher toxicity rates and higher BMI (p=0.01), and G dose 1250 mg/m2 (p< 0.01) were also observed. Conclusions: CGB is an active first-line regimen in metastatic UC. Known anti-angiogenic treatment related toxicites (bleeding, thromboembolism) are common. The risk/benefit profile of CGB in metastatic UC patients is under further study in a phase III intergroup trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Genentech Lilly Genentech Genentech
Automated large-volume extraction of circulating, cell-free DNA to improve the sensitivity of tumor biomarker detection.
Authors: Annette Nocon, Martin Horlitz, Markus Sprenger-Haussels
Journal: Journal of Clinical Oncology (2012)

19 Background: Because of its low concentration and high degree of fragmentation, the extraction and detection of tumor-derived circulating cell-free DNA (ccfDNA) is technically challenging. An optimized ccfDNA extraction method was developed and evaluated by comparison to an existing extraction protocol running on the QIAsymphony instrument and to a manual reference. Methods: 5mlEDTA plasma from healthy donors (with IRB approval) was processed. ccfDNA was bound to magnetic particles with novel surface chemistry and recovered in 150µl. As an alternative method, the “Virus cell-free 1000 protocol” using the QIAsymphony Virus/Pathogen Midi Kit was modified for the processing of higher sample volumes. ccfDNA was extracted from 4ml plasma and eluted in 90µl. The QIAamp Circulating Nucleic Acid (CNA) Kit served as a reference. ccfDNA yield was quantified by qPCR (66bp within the 18S rDNA). To determine the DNA fragment size-dependent recovery, another qPCR assay was run, quantifying four target sequences of different lengths within the APP gene. 5ml plasma was processed and eluted in 150µl. Results: The mean ccfDNA recovery (18S 66bp target; compared to the QIAamp CNA Kit) was 87% (N=6; +/-46%) for the newly developed automated extraction chemistry and 85% (N=6; +/-8%) for the modified extraction protocol. For the APP assay, ratios between the copy numbers of different target sizes were calculated. The mean ratios were: 67/476bp = 11 (N=12; +/-6.2), 180/476bp = 8.1 (N=12; +/-3.6) and 67/180bp = 1.4 (N=12; +/-0.3). Conclusions: The automated protocol versions led to an overall similar ccfDNA recovery compared to the QIAamp CNA Kit. Using the new extraction chemistry a generally improved recovery of tumor-derived circulating DNA is possible. This improvement leads to a higher sensitivity of tumor biomarker detection, which is, besides a high specificity, very important for the use of tumor biomarkers as non-invasive tool in cancer diagnosis and prognosis. The applications presented here are for research use only. Not for use in diagnostic procedures. This work has received funding from the European Union FP7 Programme under grant agreement no. 222916, SPIDIA project ( www.spidia.eu ).
NCCTG 94–72-53: Diagnostic and prognostic significance of 1p and 19q deletions in patients (pts) with low-grade oligodendroglioma and astrocytoma
Authors: J. C. Buckner, K. V. Ballman, B. W. Scheithauer, R. M. Arusell, H. E. Blair, S. M. Passe, P. D. Brown, K. A. Jaeckle, E. G. Shaw, R. B. Jenkins
Journal: Journal of Clinical Oncology (2005)

1502 Background: Tumor deletions of chromosomes 1p and 19q are associated with improved prognosis and responsiveness to chemotherapy in pts with anaplastic oligodendroglioma. Their significance in those with low-grade gliomas has not been established. Methods: Paraffin-embedded tumor tissue was obtained from 134 pts enrolled in two trials for newly-diagnosed low-grade glioma: 86–72-51, a phase III trial of 50.4 Gy vs 64.8 Gy (Shaw et al: JCO 2002;20:2267–76), and 93–72-02, a phase II trial of PCV for 6 cycles followed by radiation therapy (Buckner et al: JCO 21:251–255, 2003). 1p and 19q deletions were determined by FISH. Kaplan-Meier distributions of overall survival (OS) and progression-free survival (PFS) for pts whose tumors did or did not exhibit both 1p and 19q deletions were compared using the Wilcoxon test. Results: Of 134 pts, FISH was informative for 100. The frequency of 1p and 19q deletions by tumor histology, as well as 5-year and median OS and PFS are provided below. Conclusions: Low-grade O/OA pts have a frequency of 1p/19q deletions similar to those with anaplastic O/OA. 1p and 19q deletions are associated with superior 5-year as well as median OS and PFS in low-grade O/OA pts. FISH assessment of 1p and 19q status may assist in counseling O/OA pts regarding prognosis and treatment options. Oligo(O) Mixed Oligo Astro (OA) Astro Total FREQUENCIES TOTAL 48 30 22 100 1P- & 19Q- 27 (56%) 10 (33%) 1 (5%) 38 (38%) Not 1P- & 19Q- 21 (44%) 20 (67%) 21 (95%) 62 (62%) OS BY 1P & 19Q STATUS 5-year Deleted 96% 90% 100% 95% Not deleted 71% 60% 62% 65% median (mos.) Deleted 156 140 NR 151 Not deleted 133 87 NR 129 p-value* 0.02 (O/OA only) p-value* 0.023 (All) PFS by 1P & 19Q STATUS 5-year Deleted 80% 78% 100% 80% Not deleted 66% 36% 41% 47% Median (mos.) Deleted 96 97 NR 98 Not deleted 84 40 32 42 p-value* 0.04 (O/OA only) p-value* 0.018 (All) NR = not reached; * Wilcoxon test No significant financial relationships to disclose.
Paradoxical significance of endorectal MRI (erMRI) response to neoadjuvant chemotherapy in patients with high-risk localized prostate cancer (HRLPC).
Authors: Matt D. Galsky, Wanling Xie, Mari Nakabayashi, Robert W. Ross, Fiona M. Fennessy, Clare M. Tempany, Toni K. Choueiri, Krystal Khine, Philip W. Kantoff, Mary-Ellen Taplin, William K. Oh
Journal: Journal of Clinical Oncology (2013)

23 Background: Intermediate endpoints are desirable to expedite the integration of perioperative systemic therapy in HRLPC. erMRI response has been utilized as an endpoint in neoadjuvant trials but has not been correlated with clinical outcomes. Methods: Data were pooled from two trials exploring neoadjuvant chemotherapy in HRLPC. Trial 1 explored docetaxel for 6 months and Trial 2 explored docetaxel plus bevacizumab for 4.5 months, both prior to radical prostatectomy (RP). erMRI was done at baseline and end of chemotherapy. erMRI response was categorized as PR (&gt;50% decline in largest lesion), MR (25%-50% decline), or no response. PSA response was defined as &gt;50% decline in PSA compared to baseline. Multivariable Cox regression was undertaken to evaluate the association between clinical parameters and biochemical recurrence (BCR). Results: Trial 1 enrolled 19 patients and Trial 2 enrolled 41 patients. Among the 60 evaluable patients in the combined analysis, 20 (33%) achieved a PSA response, 16 (27%) achieved an erMRI PR, and 24 (40%) achieved an erMRI MR. Median follow-up was 4.2 years and 33 of 53 evaluable (62%) patients developed BCR. Median time to BCR from RP was 26.2 months (95% CI 12.5-53.2 mos). The multivariable model is shown in the Table. Conclusions: Response by erMRI does not correlate with decreased likelihood of BCR in patients with HRLPC treated with neoadjuvant docetaxel and may be associated with inferior outcomes. While speculative, this unexpected result could potentially be explained by a higher likelihood of erMRI response in more highly proliferative tumors. These data do not support the use of erMRI response as an endpoint in neoadjuvant chemotherapy trials. [Table: see text]
Expression and significance of EGFR in carcinoma breast and its correlation with C-erb B-2, ER, and metastasis: AIIMS experience.
Authors: R. Bhamrah, P. K. Julka, O. Nair, D. S. Bhamrah, R. Parshad, G. K. Rath
Journal: Journal of Clinical Oncology (2011)

e11035 Background: EGFR signaling pathway has shown to have a significant impact on the growth, proliferation, migration and survival of cancer cells. This study was performed on Indian patients to investigate the expression and significance of EGFR in breast cancer. Methods: The expression of EGFR, C-erb B-2, ER in 210 breast cancer patients was detected by immunohistochemistry. The correlation of EGFR expression to C-erb B-2, ER and prognosis was analyzed. Results: EGFR expression was positive in 41.4 % of breast cancer. ER was positive in 66.2% and 28.6% were C-erb B-2 positive. 19% of patients were triple negative, of these 47.5% were EGFR positive. EGFR was positively correlated to C-erb B-2 (p=0.000). Patients which over-expressed both EGFR and C-erb B-2 fared worse in terms of OS (p=0.001)and DFS(p=0.002) due to additive effect of the prognostic power. Study showed positive correlation of EGFR with Visceral metastasis (p=0.000), showing recurrences to Liver (10.3%), Lung(14.9%), Brain(5.7%) and EGFR negative patients had metastasis to Bone(17.1%). EGFR had inverse correlation to ER (p=0.000). EGFR positivity was found in 46% of ER positive and 85% of ER negative. EGFR positive but ER negative had poorer prognosis than EGFR negative but ER positive, while double negative that is EGFR and ER negative fared even worse in terms of OS. In multivariate analysis, EGFR {(p=0.000); hazard ratio of 0.357 and 95% C.I. 0.208-0.616}} and Pathological Nodal stage {(p=0.002), hazard ratio 0.409 and 95 % C.I. 0.231-0.725)} were found to be significant for OS and DFS. Conclusions: The expression of EGFR and C-erb B-2 in Breast Cancer has shown to predict a more aggressive clinical course and poor survival rate. Future trials should aim at incorporating EGFR targeted therapies in order to improve the outcome. The advent of trastuzumab treatment for breast cancer has intensified interest in C-erb B-2 status. The negative correlation of EGFR and ER may be because of bidirectional crosstalk involved in EGFR and ER pathways.
Health-related quality of life in male breast cancer patients.
Authors: H. Pfaff, P. Steffen, R. Wuerstlein, N. Harbeck, C. Kowalski
Journal: Journal of Clinical Oncology (2010)

e19576 Background: Male breast cancer is a rare disease. To our knowledge, no studies have investigated health-related quality of life (HRQoL) in male breast cancer patients. The purpose ofthis study is to investigate HRQoL in male breast cancer patients and to show how it is associated with age, type of surgery, tumor location, and cancer stage. Methods: Patients undergoing treatment for newly diagnosed breast cancer in all breast centers in North Rhine-Westphalia ( Germany) between the months of February and July during the years 2005 to 2009 were invited to self-administer a questionnaire on patients' perception of quality of care and HRQoL once they had been discharged. 14,234 patients completed the questionnaire (response rate: 88%). Of these, 55 were male. HRQoL was measured with Short-Form 36 (SF-36); clinical data were then added by medical personnel. Multiple linear regression analyses were performed to determine whether HRQoL in the SF-36 subscales varied between male and female patients. Results: Gender was found to make a significant contribution to the explanation of six of the eight SF-36 subscales (physical functioning, role-physical, bodily pain, vitality, social functioning, and mental health), after controlling for age, mastectomy/breast-conserving therapy, cancer stage, and tumor location. Conclusions: Since breast cancer is rare in male subjects, the investigators expected HRQoL to be lower in males suffering from a “female” disease. However, male patients indicated higher HRQoL in most SF-36 subscales, a finding that is consistent with the results from the healthy German reference population. Further research using breast cancer-specific HRQoL instruments to male patients is needed. No significant financial relationships to disclose.
Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes.
Authors: Nilay M Gandhi, Alexander S Baras, Enrico Munari, Sheila Faraj, Leonardo O Reis, Jen-Jane Liu, Max Kates, Mohammad Hoque, David Berman, Noah M. Hahn, Mario A. Eisenberger, George J. Netto, Mark Schoenberg, Trinity Bivalacqua
Journal: Journal of Clinical Oncology (2015)

336 Background: To evaluate gemcitabine-cisplatin (GC) neoadjuvant chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) and identify clinical parameters associated with pR. Methods: We studied 150 consecutive cases of MIBC that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index (JHH-DI) to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results: No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (p=0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, p&lt;0.01) and decreased nodal positivity rates (0% vs. 41.3%, p&lt;0.01) compared to non-responders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic non-responders (pNR) compared to the entire RC-only treated cohort. A lower pNR rate was seen in patients tolerating sufficient dosing of NAC as stratified by the JHH-DI (p=0.049), congruent with NCCN guidelines. A multivariate decision tree model demonstrated age ≤60 years and clinical stage cT2 as significant of NAC response (p&lt;0.05). Conclusions: Pathologic non-responders fare worse than patients proceeding directly to RC alone. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients most likely to benefit from GC NAC.
Safety analysis of docetaxel (T) and doxorubicin (A) followed by sequential capecitabine (X) as adjuvant chemotherapy of patients with node-positive operable breast cancer (BC)
Authors: J. I. Mayordomo, C. Madroñal, M. J. Garcia-Lopez, M. A. Burillo, V. Perez, J. Janariz, L. Murillo, R. Andres, R. Lara, J. Lambea, I. Alvarez Javier Sanz
Journal: Journal of Clinical Oncology (2005)

811 Background: T, A, and X have been shown to be very active drugs for the treatment of BC. Sequential administration of these chemotherapy agents has improved the toxicity profile versus concurrent administration. This study evaluated the safety profile of AT followed by sequential X in the adjuvant setting in patients with node-positive BC. Methods: Patients with histological diagnosis of stage II-III BC, positive regional lymph nodes, completed BC surgery, age ≥18 years, ECOG PS ≤ 2, and adequate bone marrow, renal, hepatic and cardiac function were included in the study. Prior chemotherapy, hormone therapy, and radiotherapy for BC were not allowed. Treatment: 6 courses of T 75 mg/m2 iv D1 and A 50 mg/m2 iv D1, every 21 days followed by 6 courses of X 2500 mg/m2/day po D1–14 and Vitamin B6 300 mg bid po D1–21 every 21- days. Results: Ninety-one of the 115 patients enrolled were included in this interim analysis. Median age:47 years (range 28–73), ECOG PS 0–1 100%, hormone receptor status was 64% ER/PR+, 13% ER+ and 4% PR+. Ductal infiltrating carcinoma was observed in 91% of patients. Median number of positive regional lymph nodes was 3 (maximum 30). Surgery was lumpectomy in 33% and mastectomy in 67% of patients. A total of 471 cycles of AT (median 6 per patient, range 1–6) and 243 cycles of X (median 4.5, range 1–6) were administered. Median RDIs were 99% for A, 99% for T, and 91% for X. All patients were evaluable for toxicity. During AT treatment, the main grade 3–4 toxicities per cycle were neutropenia (3%), leukopenia (2%), constipation (1%), amenorrhea (1%) and diarrhea (0.4%). There were 9 episodes of febrile neutropenia in 8 patients. During X treatment, the main grade 3–4 toxicities per cycle were neutropenia (1%), amenorrhea (3%), cutaneous toxicity (1%), hand-foot syndrome (1%) and stomatitis (0.4%). Grade 1–2 hand-foot syndrome occurred in 21% of cycles. With median follow-up of 6.7 months, no relapses were seen. Treatment of the last patient will be completed by Easter 2005, and full toxicity data on all 115 patients will be presented. Conclusions: AT followed by sequential X as adjuvant treatment of node-positive BC patients is a well-tolerated regimen. No significant financial relationships to disclose.