tbuckley/cabot-search huggingface dataset:
Multifactorial CNS relapse susceptibility in HER2-positive breast cancer patients: First results from a population-based registry study
Authors: A. Musolino, L. Ciccolallo, M. Panebianco, E. Fontana, D. Zanoni, V. De Lisi, P. Sgargi, G. Ceci, A. Ardizzoni
Journal: Journal of Clinical Oncology (2009)

1117 Background: A series of retrospective studies have reported a higher incidence of central nervous system (CNS) metastases in HER-2-positive (HER-2+) metastatic breast cancer. Trastuzumab, which does not cross the blood-brain barrier, has been associated with this increased risk. Methods: The aim of this study was to evaluate incidence, survival, and risk factors of CNS metastases in the incident breast cancer population systematically collected by the Tumor Registry of Parma Province over the 4-year period, 2004–2007. Study endpoints were: any distant metastasis as first event; CNS metastasis as first event; CNS metastasis at any time. Associations between CNS metastases and HER-2 status in the entire population and between trastuzumab and CNS metastases in HER-2+ patients (pts) were estimated. A multivariate analysis was performed to test the effect of covariates. Results: We evaluated the total resident population (n = 1500) of breast cancer pts diagnosed during the period 2004–2007 in Parma Province. Two-hundred and twenty-five pts (15%) were HER-2+ (IHC 3+/FISH amplified). Of these, 100 pts were treated with adjuvant trastuzumab-based therapy. At a median follow-up of 36 months from the diagnosis, the incidence of CNS relapse was 3% (1.3% as first recurrence). The median time to death from the diagnosis of CNS metastases was 25 months. Among the HER-2+ pts, there was a significant association between trastuzumab and subsequent CNS metastases (p = 0.02). However, in multivariate analysis, HER-2 status regardless of trastuzumab therapy was found to be the only independent predictive factor for CNS metastases (either as first or as subsequent recurrences; p &lt; 0.01). Conclusions: This is the first population-based registry study analyzing CNS metastases in breast cancer in relation to tumor biological features, systemic treatment, and clinical outcome. Based on our results, HER-2 status independently distinguishes pts with a higher risk of CNS metastases. It is however presumable that, in some cases, improvements in systemic control and overall survival associated with trastuzumab-based therapy lead to an “unmasking” of CNS relapse that would otherwise have remained clinically silent prior to a patient's death. No significant financial relationships to disclose.
Adjuvant radiotherapy use after radical cystectomy in muscle-invasive bladder cancer: A survey of U.S. radiation oncologists.
Authors: Abhishek Ashok Solanki, Brendan Martin, Mark Korpics, Christina Small, Matthew M. Harkenrider, Timur Mitin
Journal: Journal of Clinical Oncology (2017)

369 Background: Historic trials suggested significant toxicity with adjuvant radiotherapy (ART) after radical cystectomy for muscle-invasive bladder cancer (MIBC). However, recent trials have found improved locoregional control and the 2016 NCCN guidelines recommend ART consideration for select patients at high risk of local recurrence. ART practice patterns among U.S. radiation oncologists (ROs) are unknown, and we performed a survey to explore current trends. Methods: We conducted a survey of U.S. ROs regarding the management of patients with cT2-3N0M0 transitional cell MIBC. Responses were reported using descriptive statistics. Chi-square and univariate logistic regression (UVA) of clinical and demographic covariates were conducted, followed by multivariable logistic regression analyses (MVA) to identify factors predicting for ART use. Results: 277 ROs completed our survey. Nearly half (46%) use ART for MIBC. In ART-users, indications for ART include gross residual disease (93%), positive margins (92%), pathologic nodal involvement (64%), pT3 or T4 disease (46%), lymphovascular invasion (16%), and high-grade disease (13%). On UVA, ART use was associated with the number of years in practice (p=.043), pre-cystectomy RO consultation (p=0.004), primarily treating MIBC patients fit for cystectomy (p=0.009), and intensity-modulated radiotherapy (IMRT) use (p=0.009). On MVA, routine pre-cystectomy RO consultation (odds ratio [OR] 1.91, 95% confidence interval [CI]: 1.04-3.51; p=.037) and IMRT use (OR 2.77, 95% CI: 1.48-5.22; p=.002) remained associated with ART use. Conclusions: ART use is controversial in bladder cancer, yet is unexpectedly commonly used among U.S. radiation oncologists treating patients with MIBC after radical cystectomy. NRG GU001 is a randomized trial currently accruing patients with high-risk pathologic findings for observation or ART after cystectomy, and will hopefully clarify the role of ART and help identify patients benefiting from this adjuvant therapy. Whenever possible, patients should be enrolled in this study.
Trabectedin as second line and beyond in advanced leiomyosarcoma.
Authors: Arslane Skander Rahal, Olivier Mir, Julien Domont, Sylvie Bonvalot, Laurence Vilcot, Philippe Terrier, Cecile Le Pechoux, Florence Fayard, Chahinez Rahal, Axel Le Cesne
Journal: Journal of Clinical Oncology (2014)

e21522 Background: Trabectedin is approved in the European Union for patients (pts) with advanced soft tissue sarcoma (STS) after failure of anthracyclines or ifosfamide. Methods: Consecutive pts with advanced/metastatic leiomyosarcoma receiving trabectedin (1.5 mg/m2 every 3 weeks, up to 6 cycles) in our institution were included in this retrospective review. Results: Between March 1999 and January 2013, thirty six pts (16 males, median age: 54 years, range: 31-78) were started with trabectedin 1.5 mg/m2 (15% had subsequent dose reduction for grade 3/4 toxicity). Tumor grades were G1 (n=3), G2 (n=16), G3 (n=17).Primary tumor sites included extremities (n=7), abdomen/retroperitoneum (n=16), vascular (n=8) and other (n=5). Pts had received one (n=19), two (n = 13) or more (n=4) previous lines of chemotherapy. Metastatic sites were: lung (n=30), liver (n=21), bone (n=8). 24 pts had ≥2 metastatic sites. A total of 241 cycles were administered (median: 6 cycles/pt, range 1-26). Best response according to RECIST were PR (n=1), SD (n=29), for an overall clinical benefit rate (CBR: PR+SD) of 83%. All 6 pts with early progression had non extremity and grade 3 leiomyosarcoma. Grade 3-4 toxicities included neutropenia (n=11), anemia (n=2), asthenia (n=4), liver toxicity (grade 2 n=13, grade 3/4 n=7) The median PFS and OS for the whole population were 5.9 months (95% CI,5.0-8.8) and 15.1 months (95% CI, 12.1-33.1). Conclusions: Trabectedin is active therapy in advanced leiomyosarcoma, with a CBR of 83%. Liver toxicity is of concern, and should prompt dose reduction for the following cycles.
Second- and third-line chemotherapy regimens in elderly Medicare stage IV colon cancer patients.
Authors: Kaloyan A Bikov, C. Daniel Mullins, Ebere Onukwugha, Brian S. Seal, Nader Hanna
Journal: Journal of Clinical Oncology (2012)

e14056 Background: The NCCN guidelines for stage 4 colon cancer (CC4) patients provide general guidance on which chemotherapies and targeted therapies improve survival or quality of life but do not provide specific treatment (TX) recommendations. The guidelines suggest that TX is highly individualized and no single treatment is right for everyone. This leads to variation in both the number and types of TX lines, especially for elderly patients where there are larger evidence gaps. Methods: Elderly (65+) SEER-Medicare patients diagnosed with CC4 in 2003-2007 were followed through death or 2009 to examine variation across sub-groups in the number of TX lines. TX included 5-fluorouracil and (levo)leucovorin-based (5FU/LV); irinotecan (IRI) and/or oxaliplatin (OX) with/out 5FU/LV; bevacizumab, cetuximab, or panitumumab (MNCLA), alone or in combination with chemotherapy; and other TX. A hierarchy categorized treatments as: 1) IROX (IRI+OX); 2) IRI or OX; 3) 5FU/LV; 4) MNCLA without chemotherapy; and 5) other TX. Gaps in TX or changes from OX or IRI to 5FU/LV were not considered new lines. Results: Of 3,263 CC4 patients who received TX, 98% started with an NCCN-approved TX for colon cancer and 1,541 (47%) went on to second line TX. Among those with at least 2 lines of TX, the most common sequences of TX lines were OX to IRI (42%), IRI to OX (12%), 5FU/LV to OX (11%) and 5FU/LV to IRI (11%). Approximately 17% switched from chemotherapy to MNCLA alone and relatively few ever used IROX. Of second line patients, 570 (37%) had a third line of treatment. The most frequent sequence for 3 TX lines were OX to IRI to MNCLA alone (30%); 5FU/LV to OX to IRI (12%); and OX to MNCLA alone to IRI (11%). Conclusions: The number of TX lines and the sequence of TX regimens vary considerably across elderly CC4 patients. Almost all patients started with an NCCN-approved TX for colon cancer. OX to IRI for first and second line TX was the most common sequence.
Unresectable locally advanced cholangiocarcinoma treated with definitive radiation and gemcitabine.
Authors: Jesse Michael Edwards, Jason Matthew Edwards, Lowell Brian Anthony, Philip A. DeSimone, Peter Hosein, Ching-Wei David Tzeng, Erin Maynard, Malay Shah, Mahesh R. Kudrimoti
Journal: Journal of Clinical Oncology (2015)

e15127 Background: : Locally advanced Cholangiocarcinoma is typically difficult to treat if surgical resection or transplant is not an option. External beam radiation with chemotherapy is typically utilized in patients with unresectable disease. Little has been reported with regard to treatment outcome and toxicity with Gemcitabine in this low incidence disease. In this study we describe our treatment experience with patients treated with definitive chemoradiation (CRT) and systemic therapy using Gemcitabine. Methods: An IRB approved retrospective review of consecutive patients with cholangiocarcinoma was performed. Gemcitabine was given prior to CRT in 20% (N = 5) of patients and 50% (N = 13) received Gemcitabine concurrently. 5-FU was used in 50% of treatment courses (N = 13) with 38% (N = 10) given concurrently. Concurrent Gemcitabine was delivered at 400 mg/m2 q weekly 3 times and the systemic dose was 1000 mg/m2 q weekly x3 in a 4 week cycle for 4 -6 cycles. The dose of 5FU as in CI (225 mg/m2/day) or Xeloda (1700 mg/day) in divided doses during days of radiation. The sequencing of therapy included 2 patients having Chemotherapy (C) followed by CRT. CRT alone was given to 22 patients and 15 received CRT followed by C. Median dose of radiation was 5040 cGy. Results: Twenty-six consecutive patients with unresectable cholangiocarcinoma were treated from 1/2008 to 6/2014. Patient stages were T1 = 8%, T2 = 12%, T3 = 38%, and T4 = 42%. Lymph nodes were involved in 46% of patients (N = 12). Median age was 64 years. Mean follow up was 11 months. Grade 3+ acute and late GI toxicity were both found to be 8% with no treatment related mortality. Overall survival was significantly improved in patients who received Gemcitabine 73% vs. 39% at one year and 38% and 18% at two years (p < 0.05). Dose of radiation did not correlate with treatment outcome. No differences in acute or late toxicity were noted between regimens. Conclusions: The use of Gemcitabine given prior to or during radiation therapy was associated with greater overall survival benefit with minimal change in toxicity. This is a study of a low incidence cancer with limited patient numbers but may provide groundwork for future study.
Lung cancer (LC) patient (Pt) and caregiver (CG) perceptions of multidisciplinary (multiD) care.
Authors: Satish Kedia, Kenneth Daniel Ward, April L Nellum, Siri A Digney, Kristina S Roark, Tessa R Kyle, Stephanie Clark, Stephanie W Boyd, Fayre J Crossley, Orion T Osborne, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2014)

e17684 Background: LC care involves many different medical specialists. Inefficiencies in the prevailing serial care model of sequential referrals and evaluation has led experts to advocate the multiD care model in which Pts, CG, and key specialists concurrently develop consensus care plans. MultiD care is rare in community settings. We sought care improvement suggestions from Pts and CG in a community multiD thoracic clinic (CMTC). Methods: Qualitative analysis of focus groups (FG) of Pt and informal CG dyads. Pts had experienced the serial care model, and been seen at least once in a CMTC with concurrent medical oncology, thoracic surgery, radiology and pulmonology staffing and coordination by a nurse navigator. FG were conducted by a medical anthropologist and clinical psychologist unaffiliated with the CMTC. Transcribed data were analyzed in Dedoose qualitative software using Colaizzi’s 7-step approach. Recurring themes and variants were identified. Results: Overlapping themes within and between the 5 Pt:CG FG dyads were: a preference for the multiD approach, perceived high level of benefit from physician collaboration, and belief that a central contact person (the nurse navigator) decreased confusion, stress, and anxiety. Many Pts and CG reported negative prior experiences with serial care ranging from the confusion of having multiple doctors, insensitive disclosure of the disease, delays in diagnosis and treatment, and mistreatment. Under multiD care, the dyads reported less redundancy in testing procedures. MultiD care was seen as more efficient and convenient with a single site to visit. Suggested improvements were: better initial explanation of the process of care, and better physician-to-physician and physician-to-patient communication. Conclusions: This qualitative study provides Pt-centered insights into LC care delivery, which may reinforce the knowledge infrastructure supporting multiD care. We plan additional FG of clinicians, hospital administrators and representatives of third party payers. Pts N=22 CG N=24 Sex M/F 11/11 6/18 Race AA/CA 7/15 7/17 Education High school/college/postgraduate 11/9/2 7/12/5 Location in spectrum of care Active Rx Last Rx <6months Last Rx >6 months 9 11 2 10 8 3
A phase I trial of lapatinib in combination with carboplatin in patients with platinum sensitive recurrent epithelial ovarian cancer
Authors: K. J. Kimball, T. M. Numnum, J. M. Estes, T. O. Kirby, M. N. Barnes, R. D. Alvarez
Journal: Journal of Clinical Oncology (2007)

14106 Objective: Lapatinib is an inhibitor of EGFR and ErBb-2 tyrosine kinase. It has demonstrated anti-tumor activity in preclinical trials. Early trials evaluated toxicities and doses in several tumors types, however very few ovarian cancer patients have been included in lapatanib trials. The primary objective of this study was to determine the nature and degree of toxicity as well as the maximum tolerated dose (MTD) of Lapatinib in combination with carboplatin when used as second line therapy for platinum sensitive, recurrent ovarian or primary peritoneal carcinoma. The secondary outcome includes preliminary evaluation of response to therapy. Methods: After obtaining IRB approval, patients with measurable, recurrent, platinum sensitive epithelial ovarian or primary peritoneal carcinoma were eligible for enrollment. Patient cohorts were treated with intravenous (IV) carboplatin (AUC 6) every 21 days in combination with escalating dosages of daily oral lapatinib for 6 planned cycles. Toxicity was assessed using NCI Common Terminology Criteria for Adverse Events. Response and time to documented progression were also monitored. Results: Nine patients have been enrolled in 2 cohorts to date. Six women with recurrent cancer were administered eighteen cumulative cycles of IV carboplatin and 750 mg of oral lapatinib and were evaluable for toxicity data. The most common toxicity was hematologic with 8 (44%) cycles effected by grade 3 or 4 neutropenia or thrombocytopenia. Two patients were taken off the study secondary to excessive delay for hematologic depression. The dose of carboplatin was reduced to an AUC 5 in the second cohort due to excessive hematologic toxicity and treatment delay. Grade 3 nonhematologic toxicities consisted of abdominal pain (38%), indigestion (6%), fatigue (6%), and urinary frequency (11%). One patient withdrew due to abdominal pain not related to the study drug. Two subjects were evaluable for response. As indicated by biochemical and radiographic examination, both had a complete response and have no evidence of disease. Conclusions: Lapatinib, in combination with IV carboplatin at an AUC 5, portrays an acceptable toxicity profile and antitumor activity. Accrual to cohorts of escalating lapatinib doses is ongoing. No significant financial relationships to disclose.
Trastuzumab (TRA) in combination with different first-line chemotherapies for treatment of HER2-positive metastatic gastric or gastroesophageal junction cancer (MGC): Findings from the German noninterventional observational study HerMES.
Authors: Susanna Hegewisch-Becker, Enno Moorahrend, Hendrik Kröning, Volker Petersen, Carla Hannig, Dirk Pott, Christian Tirier, Christian A. Lerchenmuller, Rudolf Schlag, Wolfgang Schneider-Kappus, Volker Kaechele, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2012)

4065 Background: The international phase III study ToGA has recently shown that TRA is effective in prolonging survival in HER2-positive MGC. However, few data are available for TRA as part of routine clinical practice. Methods: This non-interventional observational study was conducted to evaluate the efficacy, safety and feasibility of TRA in previously untreated pts with HER2-positive MGC. Results: Between Apr 2010 and Jan 2012, data from 110 pts were collected. All pts were evaluable for safety. Baseline pt characteristics were as follows: median age 63 yrs (range 29–88); gender (male 70%; female 29%); ECOG PS (0: 25%; 1: 50%; 2: 15%; 3: 5%); distant mets (91%); liver mets (54%), lymph node mets (35%); peritoneal carcinomatosis (23%). The median duration of TRA treatment was 4.4 months (0–17.1). According to the schedule of chemotherapy TRA was administered every 2–3 wks in a median dose of 4–6 mg/kg BW. Only 28% of pts received TRA according to the label in combination with cisplatin and 5-FU or capecitabine. The remainder received: cisplatin, 5-FU and leucovorin (17%); 5-FU, leucovorin, oxaliplatin and docetaxel (8%); 5-FU, leucovorin and oxaliplatin (7%); capecitabine (6%); other combinations (25%); TRA monotherapy (7%). Although most pts didn’t receive cisplatin-based therapy, preliminary median progression-free survival was 6.8 months, thus comparable to the ToGA data. Most common adverse events (AEs, all grades) were diarrhoea (7%), vomiting (5%) and nausea (5%). Most common grade 3/4 AEs were vomiting (3%), nausea (2%) and fatigue (2%). Health-related quality of life as assessed by EORTC QLQ-C30 and QLQ-STO22 remained stable during observation time. An updated analysis of approx. 200 pts will be presented at the meeting. Conclusions: TRA combined with diverse chemotherapies is safe and effective in the routine treatment of MGC. Cisplatin-free less toxic regimens are feasible and equally effective. The results are in line with those from the ToGA trial and suggest that treatment with TRA should be regarded as standard of care for pts with HER2-positive MGC.
Patient Inducements — High Graft or High Value?
Authors: Krisda H. Chaiyachati, David A. Asch, David T. Grande
Journal: New England Journal of Medicine (2017)

U.S. law prevents health care providers from using inducements to increase demand for care or encourage selection of one provider over another. But given recent changes in health care, perhaps inducements that support receipt of high-value services should be permitted.
Association of bone marrow plasma cell infiltration pre-auto transplant with adverse outcomes in multiple myeloma.
Authors: Qaiser Bashir, Simrit Parmar, Yvonne Dinh, Sofia Qureshi, Gabriela Rondon, Uday R. Popat, Yago Nieto, Roy B. Jones, Richard E. Champlin, Muzaffar Qazilbash, Nina Shah
Journal: Journal of Clinical Oncology (2012)

8102 Background: Auto-stem cell transplantation (SCT) has become the standard of care for eligible patients (pts) with multiple myeloma (MM). However, the impact of bone marrow (BM) plasma cell (PC) percentage before SCT is not yet known. Methods: Retrospective review of 1489 MM pts who underwent auto-SCT from 7/8/98 – 12/31/2010 with post-induction, pre-SCT BM biopsy information available. Pts were divided into 2 groups: &lt;10% PC infiltration (“PC low”) and &gt;10% PC infiltration (“PC high”). Progression-free (PFS) and overall (OS) survivals were estimated by the Kaplan-Meier method. Log-rank test was performed to test differences in survival. Results: 1489 pts were studied. 1174 pts had &lt;10% involvement of BM by PCs and 315 had &gt; 10% involvement. For pts in the PC low group, 32% had a CR, 20% had a VGPR, 31% had a PR, 13% had &lt;PR and 3% had progressive disease (PD) after SCT. For pts in the PC high group, 11% had a CR, 14% had a VGPR, 48% had a PR, 21% had &lt;PR and 5% had PD after SCT. Median PFS was significantly shorter for the PC high group vs the PC low group (24.8 vs 29.5 months, p=0.05), as was median OS (52.5 vs 79.4 months respectively, p&lt;0.001). When only pts who had a PR to induction were examined, there was a significant difference in both PFS (24.4 vs 33.2 months, p=0.04) and OS (58.3 vs 81.2 months, p =0.002) for the PC high vs PC low groups, respectively. For the 1299 (87%) pts treated in the era of novel therapeutics (after 2000), the differences between the PC high and PC low groups were maintained for both PFS (24.4 vs 29.5 months respectively (p=0.029)) and OS (54.8 vs 88.4 months respectively, p&lt;0.001). Chemo-mobilization before SCT did not improve PFS or OS but this was done in only 44 (14%) of PC high pts. Conclusions: PC BM infiltration before auto-SCT is associated with a worse outcome. This finding persists in pts with a PR before SCT. Thus BM disease burden may further stratify pts with a PR. Though additional therapy did not significantly change the outcome for pts with high PC burden, this was done only in a minority of pts. Additionally, differences between PC high and PC low groups are maintained despite new salvage agents over the last 10 years. Further prospective study is warranted to determine the true impact of BM PC infiltration.
Systematic Review of the Published Evidence on the Pharmacokinetic Characteristics of Factor VIII and IX Concentrates
Authors: Menchen Xi, Tamara Navarro-Ruan, Sunil Mammen, Victor S. Blanchette, Cedric R. Hermans, Massimo Morfini, Peter W. Collins, Kathelijn Fischer, Ellis J. Neufeld, Guy Young, Kaan Kavakli, Paolo Radossi, Amy Dunn, Lehana Thabane, Alfonso Iorio
Journal: Blood (2014)