tbuckley/cabot-search huggingface dataset:
Choosing wisely: The utility and costs of routine staging imaging in breast cancer.
Authors: Samuel Merrill, Pamela Stevens, Claire F. Verschraegen, Marie Wood
Journal: Journal of Clinical Oncology (2015)

e17800 Background: Occult metastasis in clinical stage I/II breast cancer is rare, but its presence could substantially change management. The American Society of Clinical Oncology (ASCO) recommends against routine staging imaging for asymptomatic stage I/II breast cancer patients as scans have questionable benefit beyond history, physical exam, and basic lab studies. To assist clinicians in providing high-value care we examined the utility and costs of modern CT-based staging to detect occult metastasis in stage I/II breast cancer. Methods: PET-CT and CT with bone scan performed for breast cancer staging over 2 years (10/1/2012 – 9/30/2013) at University of Vermont Medical Center (UVMMC) were identified by CPT and ICD-9 codes. Scans were categorized as indicated if patients were clinical stage III/IV, had recurrence, or had symptoms suggestive of advanced cancer; scans were non-indicated if no such factors were present. Scan results and subsequent interventions were determined by clinician chart review. Costs of imaging and procedures were estimated from hospital charge data using the charge-cost ratio method. Results: Between 10/1/2011 – 9/30/2013 683 breast cancer patients were evaluated at UVMMC. Thirteen percent (66/490) of all patients with clinical stage I/II cancer had staging scans, with lymph node involvement in 59/66. Staging was indicated by symptoms or occult stage III cancer in 18% of patients scanned (12/66). No cases of metastatic breast cancer were identified by non-indicated staging imaging (0/54). Non-indicated staging scans had a false positive rate of 37% (20/54), and precipitated two invasive diagnostic procedures. The cost of the non-indicated staging was $265,236 and further evaluation of false-positive scans cost an additional $59,741. Including staging and follow up evaluations, the total cost of non-indicated staging was $6,018 per person with no discovery of metastatic disease. Conclusions: Our data support the current ASCO recommendations and demonstrate that routine staging imaging for clinical stage I/II breast cancer patients has a high false positive rate, high costs, and low rate of metastatic disease detection regardless of nodal involvement.
A randomized phase 3 trial of thalidomide and prednisone (TP) as maintenance therapy following autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM): An updated analysis of the NCIC Clinical Trials Group MY10 trial.
Authors: Annette E. Hay, Suzanne Trudel, Nizar J. Bahlis, Darrell White, Waleed Sabry, Andrew Belch, Tony J. Reiman, Jean Roy, Chaim Shustik, Michael J. Kovacs, Jonathan Sussman, Donna Ellen Reece, Martha Lacy, Ralph M. Meyer, Lois E. Shepherd, Kate Whelan, Liting Zhu, Judy-Anne W. Chapman, A. Keith Stewart
Journal: Journal of Clinical Oncology (2014)

8591 Background: Primary analysis of the MY.10 trial (Stewart, Blood 2013) demonstrated, with a median f/u of 4.1 yrs, MM patients completing ASCT and randomized to receive 4 yrs of TP experienced superior progression free survival (PFS) and poorer quality of life scores as compared with those randomized to observation. No differences in overall survival (OS) were detected (HR=0.77). We now report long term survival. Methods: From 2002-09, 332 patients were enrolled. Primary endpoint was OS; secondary endpoints were myeloma-specific PFS (MS-PFS) defined as time from randomization to progressive myeloma, and PFS which also includes death without myeloma progression as an event. Trial arms were compared with a stratified (by age and response to transplant) log-rank test; all analyses were by intent-to-treat. This report is based on the final 2013 December 20 locked database. Results: Median age at study entry was 58 years. Among 166 TP patients, 8 (5%) completed 4 years of at least one drug. With a median follow-up of 6.1 years (range 0 – 10.4), TP continued to be associated with superior MS-PFS and PFS. No differences in OS were detected. There were 17 second cancers in 13 TP patients (6 skin, 2 acute myeloid leukemia (AML), 9 solid tumors) compared with 9 in 8 observation patients (3 skin, 2 AML / myelodysplasia, 4 solid tumors). A higher incidence of thromboembolic events was observed in the TP arm (12 vs. 1, p = 0.003). Conclusions: A PFS advantage of TP maintenance therapy continues to be seen at 6 years without improvement in OS. As the HR for OS has increased from 0.77 with median f/u of 4.1 yrs to 0.88 with median f/u of 6.1 yrs, we expect that longer f/u will not permit detection of a difference in OS. Our data are consistent with other data showing that PFS is an unreliable surrogate for OS when evaluating maintenance therapies for MM patients. Clinical trial information: NCT00049673. 6 yr estimate p-value HR (95% CIs) Median FU Maintenance N = 166 Observation N = 166 6.1 yr 4.1 yr MS-PFS 28% 10% <0.0001 0.58 (0.46, 0.75) 0.56 (0.42, 0.73) PFS 26% 9% <0.0001 0.58 (0.45, 0.73) 0.56 (0.43, 0.73) OS 56% 49% 0.41 0.88 (0.65, 1.19) 0.77 (0.53, 1.14)
An evaluation of changes in biological markers (ER, PgR, or Ki67) after neoadjuvant chemotherapy (ET: epirubicin and docetaxel) in operable breast cancer
Authors: R. Tashima, R. Nishimura
Journal: Journal of Clinical Oncology (2006)

10613 Background: Neoadjuvant chemotherapy (NAC) is a valid option not only for advanced breast cancer but also for operable breast cancer. It was reported that disease-free and overall survival after NAC were equivalent to those after adjuvant therapy. The role of biological markers for the prediction of NAC may be evaluated using pathological responsiveness. In this study, we investigated the changes in biological markers such as estrogen receptor (ER), progesterone receptor (PgR), or Ki67 after NAC. Methods: Eligible patients (pts) were newly diagnosed with large primary tumors &gt; 3 cm or positive nodes. Fifty-two pts were enrolled and received epirubicin 60 mg/m 2 followed by docetaxel 60 mg/m 2 every 3 weeks for 4 cycles before surgery. In 51 cases out of the pts, pre-treatment needle biopsies and surgical specimen were analyzed for expression of ER, PgR, Her-2/neu, p53 and Ki67 by immunohistochemistry, and these data were compared to the pathological response. The pathological response was evaluated using the criteria of Japan Breast Cancer Society. Results: The median age was 47 (range, 29–67) and the mean tumor size was 5.2cm (range, 1.5–14.5). The clinical response was 86%; the BCS rate was 73% and pathological response was 31% including 3 cases with pCR. Regarding changes in biology after NAC, an average rate of ER positive cells significantly fell in 37% from 47% and that of PgR positive cells also fell in 14% from 32%. Most of cases, whose tumors were changed to ER/PgR negative from ER/PgR positive, were premenopausal women accompanied with amenorrhea during the treatment. Patients with lower ER, PgR, or a higher proliferation had a significantly greater benefit from NAC. The overexpression of Her2 was not correlated to pathological response, while p53 staining had a predictive value. And patients with positive nodes had a significantly favorable disease-free survival. Conclusions: The clinical effect of NAC (ET regimen) and the BCS rate by NAC were high. Although the rates of ER and PgR positive cells and proliferation were significantly reduced by NAC, a lower ER, PgR, or a higher proliferation might reflect a good pathological response. A negative change of ER or PgR by NAC might correlate with amenorrhea in premenopausal pts. No significant financial relationships to disclose.
Activity of chemotherapy in a series of patients with locally advanced or metastatic pleomorphic rhabdomyosarcoma: A retrospective analysis.
Authors: Michela Libertini, Nadia Hindi, Salvatore Provenzano, Rossella Bertulli, Roberta Sanfilippo, Silvia Stacchiotti, Elena Palassini, Elena Fumagalli, Giacomo G. Baldi, Bruno Vincenzi, Angelo Paolo Dei Tos, Alessandro Gronchi, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2014)

10592 Background: Pleomorphicrhabdomyosarcoma (pRMS) of the adult is a rare and controversial sarcoma marked by skeletal muscle differentiation. Few data are available on the efficacy of chemotherapy in pRMS, and no definitive data support the efficacy of treatment strategies usually applied for other rhabdomyosarcoma subtypes. We reviewed response to chemotherapy in patients with pRMS treated within the Italian Rare Cancer Network (RTR). Methods: We retrospectively reviewed adult patients with pRMS treated at our institution or within RTR since 2001, focusing on patients treated with chemotherapy. Response was evaluated by RECIST. Results: Fifty-seven patients with pRMS were selected. Thirty-six of 57 patients received chemotherapy. Among them, 26 patients (M/F: 21/5–mean age: 55; range 21-80 years; locally advanced/metastatic at the onset 18/8) were evaluable for response. Twelve of 18 patients progressed to metastatic disease after local treatment. 12/20 patients in the advanced phase were evaluable having received at least one chemotherapeutic regimen. Conclusions: Our data suggesta moderate activity of chemotherapy in pRMS. Interestingly, 3/3 pre-treated patients who received gemcitabine in the advanced setting had a PR. Treatment Patients with locally advanced disease Subtotal CR PR SD PD Anthracycline-based 2 1 3 3 9 Anthracycline-based + concomitant RT 0 2 7 0 9 Patients with metastatic disease Treatment Prior chemotherapy CR PR SD PD Subtotal Anthracycline-based 2 0 1 2 4 7 Ifosfamide-based 5 0 0 0 5 5 Gemcitabine 3 0 3 0 0 3 Trabectedin 2 1 0 0 1 2 Topotecan 1 0 0 1 0 1 Metronomic cyclophosphamide 1 0 0 0 1 1 Metronomic etoposide 1 0 0 0 1 1
Immune monitoring of phase II trial of hu14.18-IL2 for patients with metastatic melanoma.
Authors: Mark R. Albertini, Jacquelyn A Hank, Brian Christopher Gadbaw, Jordan Kostlevy, Jennifer Haldeman, Jacek Gan, KyungMann Kim, Jens C. Eickhoff, Stephen Gillies, Paul M. Sondel
Journal: Journal of Clinical Oncology (2012)

e19047 Background: Phase I testing of the hu14.18-IL2 immunocytokine (IC) in patients (pts) with melanoma showed immune activation, reversible toxicities, and a maximal tolerated dose (MTD) of 7.5 mg/m 2 /day. Methods: In this phase II study, 14 metastatic melanoma pts were scheduled to receive hu14.18-IL2 at 6 mg/m 2 /day as 4-hour intravenous infusions on days 1, 2 and 3 of each 28 day cycle. Pts with stable disease (SD) or regression following cycle 2 could receive 2 additional treatment cycles. The primary objective was to evaluate anti-tumor activity and response duration. Secondary objectives evaluated adverse events and immunologic activation. Results: All pts received 2 cycles of treatment. One pt had a partial response (PR) [1 PR of 14 pts = response rate of 7.1%; confidence interval 0.2%-33.9%] and 4 pts had SD and received cycles 3 and 4. The PR and SD responses lasted 3-4 months. All toxicities were reversible. Analysis of serum IC for all pts showed a mean value of 1.42 ug/ml on C1D1 and 1.38 ug/ml on C1D3. Pts had a peripheral blood lymphocytosis on day 8 and increased C-reactive protein (CRP). A significant increase in sIL2R levels was seen in all courses from baseline to day 3 (p&lt;0.001 for both courses 1 and 2). Infusion of the IC into these pts enabled their serum to mediate antibody dependent cell-mediated cytotoxicity using the circulating IC. Eight pts developed a “positive” anti-idiotype antibody against hu14.18-IL2 based on a bridging assay, and 13 developed a detectible anti-idiotypic antibody based on a binding inhibition assay. There was no significant effect of this anti-idiotypic antibody response on the in vivo level of hu14.18-IL2. While one PR in 14 pts met protocol criteria to proceed to stage 2 and enter 16 additional pts, we suspended stage 2 due to limited availability of hu14.18-IL2 at that time and the brief duration of PR and SD. Conclusions: We conclude that subsequent testing of hu14.18-IL2 should involve melanoma pts with minimal residual disease based on compelling preclinical data as well as the confirmed immune activation with some antitumor activity in this study. In addition, the demonstrated immunological activation of hu14.18-IL2 with manageable toxicities suggests the potential for combination treatments.
Pegaspargase Plus Gemcitabine, Oxaliplatin(P-Gemox) and Thalidomide Versus Aspermetdex Regimen for the Patients with Early or Advanced/Relapsed Extranodal Natural Killer/T Cell Lymphoma: Interim Analysis of a Prospective,Multicenter, Randomized, Phase III Non-Inferiority Clinical Trial
Authors: Yan Gao, Huiqiang Huang, Yujing Zhang, Hang Su, Xiaoxiao Wang, Bing Bai, Yunhong Huang, Yuhuan Gao, Liping Su, Xiaoxia Chu, Wenyu Li, Junyi Zhang, Qiaohua Zhang, Liansheng Zhang, Xiaohua Hu, Liqun Zou, Zhiming Li, Wenqi Jiang
Journal: Blood (2016)
Standardized radiofrequency ablation (sRFA) ≥ 45 minutes (m) plus lyso-thermosensitive liposomal doxorubicin (LTLD) for solitary hepatocellular carcinoma (HCC) lesions 3-7 cm: A retrospective analysis of phase III HEAT study.
Authors: Riccardo Lencioni, Won-Young Tak, Min Hua Chen, Richard S. Finn, Morris Sherman, Lukas Makris, Micheal O'Neal, William Simonich, Dieter Haemmerich, Robert Reed, Nicholas Borys, Ronnie Tung Ping Poon, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2014)

e15143 Background: The outcome of RFA for HCC tumors >3cm remains unsatisfactory, with high recurrence rates suggesting that RFA alone often fails to eradicate all disease. We previously conducted a double-blind randomized controlled trial (DBRCT) of RFA ± LTLD, the HEAT Study. LTLD is given by iv infusion. The liposomes selectively localize in and around tumors due to the enhanced permeability and retention properties of tumors. When these areas are heated to >40°C, the liposomes quickly break down and release a high concentration (conc) of the heat-enhanced cytotoxic doxorubicin (dox). We randomized 701 patients (pts) who had <4 unresectable HCC lesions, with at least one ≥3cm and none >7cm. No minimum RFA heating time was required. The primary and a key secondary endpoint were progression-free survival (PFS) and overall survival (OS). RFA + LTLD was safe, with reversible myelotoxicity similar to dox. Median PFS was about 14 months in both arms and median OS was about 53 months in both arms. Pts with multiple lesions did not benefit from adding LTLD to RFA. A computational modeling study of LTLD and mild (43ºC) heat found that the conc of dox in liver tumor tissue increases with duration of heating, but it takes 45m to deliver 75% of maximum conc. Also, a preclinical study of LTLD in healthy pigs confirmed that longer RFA heat time results in higher dox liver conc. Methods: Post hoc multivariate Cox regression analysis was performed on the HEAT study subgroup of 446 pts with a solitary lesion, with 7 prognostic factors (RFA heat time >45m or <45m, age, etiology, lesion diameter, Child-Pugh class, region, RFA device) considered in the model. Results: Both univariate and multivariate analyses suggest that the efficacy of RFA + LTLD is optimized by standardizing RFA to provide ≥ 45m heat time. Among the 285 pts with a solitary lesion who received sRFA, the OS hazard ratio is 0.64 (95% CI: 0.41 - 1.00, P = 0.0495); medians have not yet been reached based on the 86 deaths to date. Conclusions: A DBRCT of sRFA ± LTLD is warranted. We will soon initiate the 550-pt OPTIMA study to evaluate ≥ 45m RFA ± LTLD in pts with a single 3-7cm lesion. Clinical trial information: NCT00617981.
Comparison of veterans diagnosed with left and right colon cancer over a period of 10 years.
Authors: Ying Margie Tang, Fengming Zhong, Neal Patel, Victor Tsu-Shih Chang, Melanie L. Gonzalez, Emma R Paz-Querubin, Jan Einhorn, Basil Kasimis
Journal: Journal of Clinical Oncology (2014)

e14616 Background: We studied the characteristics and survival for patients (pts) with left and right sided colon cancer in Veterans. Methods: In an IRB-approved protocol, we reviewed the records of pts diagnosed with colon cancer at a VA medical center from 01/01/2003 to 12/31/2012. Demographics, grade, stage, ECOG performance status (PS), CEA, Hemoglobin (HGB), and Albumin (ALB) at diagnosis (dx), diagnosis by screening, treatment, and cause of death were studied. Statistical analysis was performed with SAS 9.2 and Stata v11.0. We compared the characteristics and survival in pts with left and right sided colon cancer. Results: There were 296 pts with colorectal cancer with median (M) age of 69 years. 126 pts had left sided colon cancer with M age of 67 years. 88 pts had right sided colon cancer with M age of 70 years. 80 pts with rectal cancer and 2 pts with unclear colorectal sites were excluded from this analysis. For left sided colon cancer, 51 pts (40%) were stage I with median survival (MS) of 1548 days, 25 pts (20%) were stage II with MS of 1449 days, 23 pts (18%) were stage III with MS of 1471 days, and 22 pts (17%) were stage IV with MS of 420 days. For right sided colon cancer, 23 pts (26%) were stage I with MS of 979 days, 23 pts (26%) were stage II with MS of 1822 days, 19 pts (22%) were stage III with MS of 797 days, and 16 pts (18%) were stage IV with MS of 373 days. Comparison is summarized in the table below. Conclusions: In this cohort, the patients with right sided colon cancer had lower hemoglobin level, higher grades, and shorter median survival compared to those with left sided colon cancer. Further studies will be conducted to confirm these findings. Supported by NJCCR. Left Right p M Age (years) 67 (48-88) 70(43-90) NS Numbers (No.) of pts 126 88 HGB (gm/dl) 12.5(6.5-16.5) 11.5 (6.1-16.7) <.003 ALB (gm/dl) 4.0(2.1-4.7) 3.8 (1.4-4.9) NS CEA (ng/ml) 2.25(0.2-647) 2.4(0-2071) NS Grade I/II/III (No. of pts) 12/82/19 6/51/27 <.04 Diagnosis by screening (%) 29% 29% NS Death from cancer (%) 52% 55% NS Median survival (days) 1293(36-3987) 916 (5-4004) 0.036 Stage distribution (No. of pts) 51/25/23/22 23/23/19/16 NS Surgery (% of pts ) 85% 90% NS Chemotherapy (% of pts) 29% 27% NS
Feasibility of allogeneic stem-cell transplantation after azacitidine bridge in higher-risk myelodysplastic syndromes and low blast count acute myeloid leukemia: results of the BMT-AZA prospective study
Authors: M.T. Voso, G. Leone, A. Piciocchi, L. Fianchi, S. Santarone, A. Candoni, M. Criscuolo, A. Masciulli, E. Cerqui, A. Molteni, C. Finelli, M. Parma, A. Poloni, A.M. Carella, F. Spina, A. Cortelezzi, F. Salvi, E.P. Alessandrino, A. Rambaldi, S. Sica
Journal: Annals of Oncology (2017)
Retrospective analysis of the effects of systemic chemotherapy to the ovarian metastases from colorectal cancer.
Authors: Katsutoshi Sekine, Tetsuya Hamaguchi, Hirokazu Shoji, Shoko Nakamura, Takahiro Miyamoto, Atsuo Takashima, Yoshitaka Honma, Satoru Iwasa, Ken Kato, Kenta Takahashi, Tomoyasu Kato, Yukihide Kanemitsu, Narikazu Boku
Journal: Journal of Clinical Oncology (2017)

731 Background: Ovarian metastases from colorectal cancers are relatively rare. Since most ovarian metastases are also associated with other metastatic sites, the prognosis is reported to be poor. It is not fully understood whether the response to systemic chemotherapy of ovarian metastases differs from that to other metastatic sites. Methods: We retrospectively reviewed the clinical data of patients with ovarian metastases from colorectal cancer treated at our hospital between January 2006 and December 2015. Results: Among the 635 female patients with relapsed or metastatic colorectal cancer, 57 (9.0%) had ovarian metastases before the first-line treatment; 37 patients received palliative chemotherapy, and 20 patients were initially treated by surgical resection. In addition, 38 cases of ovarian metastases developed after the initiation of first-line chemotherapy. Overall, 95 patients (15.0%) with ovarian metastases were treated during this period. The objective response rate for systemic chemotherapy of ovarian metastases was lower than that for other metastatic sites (22.9 % vs 60.9 % for first-line, 3.4 % vs 13.6 % for second-line, 11.1 % vs 26.6 % for third-line, and 0% vs 18.2 % for fourth-line, respectively). After the initiation of chemotherapy, surgical resection of ovarian metastases was positively associated with a longer overall survival (26.8 months for cytoreductive surgery and 17.0 months for only systemic chemotherapy, p &lt; 0.001), especially when the other metastatic sites had not progressed after chemotherapy. Conclusions: Ovarian metastases are less responsive to systemic chemotherapy compared to the extra-ovarian metastases. Our data also suggest that multi-disciplinary treatment strategy including systemic chemotherapy and cytoreductive surgery might improve the prognosis of ovarian metastases.
Phase I study of oral selective c-Met inhibitor EMD 1214063 in pts with advanced solid tumors.
Authors: Gerald Steven Falchook, David S. Hong, Hesham M. Amin, Siqing Fu, Sarina Anne Piha-Paul, Filip Janku, Vivek Subbiah, Aung Naing, Jennifer J. Wheler, Manfred B. Klevesath, Karola Köhler, Andreas Johne, Friedhelm Bladt, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2013)

2506^ Background: To perform the first-in-human study of EMD 1214063, a highly selective, reversible, ATP-competitive c-Met inhibitor that causes growth inhibition and regression of hepatocyte growth factor-dependent and -independent tumors in preclinical models. Methods: Primary objective of this dose-escalation study (3+3 design) was to establish the EMD 1214063 MTD (NCT01014936). Secondary endpoints included safety, PK, antitumor effect, and pharmacodynamics (Pd). Eligible pts had advanced solid tumors not amenable to standard therapy. Pts received once daily (QD) oral EMD 1214063 on 1 of 3 regimens (all 21-d cycles): d 1–14 followed by 7-d rest (R1), continuous 3 times weekly (R2), or d 1–21 (R3). An optimized formulation (OF) was introduced in Aug 2011. Results: 100 pts were treated (R1:42; R2:41; R3:17). On the initial formulation, doses were escalated from 30–230 mg/d in R1, and 30–115 mg/d in R2. OF data are available for 30–400 mg/d in R1, 60–175 mg/d in R2, and up to 500 mg/d in R3. C max and AUC increased with dose; OF showed higher bioavailability. 4 pts experienced DLTs: G4 lipase and G3 amylase increase (R1; 115 mg/d), G3 lipase increase (R2; 60 and 115 mg/d), and G3 nausea and vomiting (R2; 130 mg/d OF). Other G3 drug-related AEs included G3 peripheral edema (1 pt in R3, 300 mg/d OF). G2 drug-related AEs (R1-3) included fatigue (n=8), lipase increase (n=3), nausea (n=2), decreased appetite (n=2), vomiting (n=2), and neutropenia (n=2). 80% pts had no drug-related AE &gt;G1. Pre- and on-treatment tumor biopsies showed inhibition of phospho-c-Met levels in 13/15 evaluable pts. 2 unconfirmed partial responses were observed (NPC and NSCLC). SD &gt;4 mo was observed in 15 pts. 1 pt with sarcomatoid bladder cancer and multiple MET copies due to Chr 7 polysomy had SD for &gt;32 mo. PK/Pd analysis suggested that 500 mg QD was sufficient for target inhibition, consistent with preclinical models. In the 500 mg QD cohort, which was expanded to 12 pts, no DLTs were observed. 500 mg QD was confirmed as the recommended phase 2 dose (RP2D). A formal MTD was not identified despite dose escalation beyond 500 mg. Dose escalation above 1000 mg is not anticipated. Conclusions: EMD 1214063 was safe and demonstrated antitumor activity. 500 mg QD was determined as the RP2D. Clinical trial information: NCT01014936.