tbuckley/cabot-search huggingface dataset:
Defining the chemotherapy (CT) response in well-differentiated (WD) and dedifferentiated (DD) liposarcomas (LPS) of the retroperitoneum (RP): A tertiary referral cancer center experience.
Authors: Neeta Somaiah, Diogo Bugano Diniz Gomes, John E Madewell, Wei-Lien Wang, Anthony Paul Conley, Vinod Ravi, Dejka M. Araujo, Joseph A. Ludwig, Robert S. Benjamin, Shreyaskumar Patel
Journal: Journal of Clinical Oncology (2014)

10583 Background: WD/ DD LPS is the most common LPS subtype, predominantly arising in the RP. Surgery is the primary treatment, but recurrences are frequent. CT is usually reserved for unresectable cases and the reported RECIST response rate (RR) is 12% (Italiano et al. 2012). However, in our experience, RECIST does not capture morphological changes consistent with response on imaging. Our objective was to review RR to CT and describe radiologic patterns of response. Methods: Search of the tumor registry for patients (pts) with RP WD/DD LPS who received CT at MD Anderson Cancer Center from 2003-2013 yielded 48 pts. The pathology database registered 316 new pts with RP WD/DD LPS in the same time frame. Data was collected from the electronic charts and the Social Security Death Index. Here we report the results for the first 48 pts; updated analysis with RECIST and imaging characteristics by an independent radiologist will be presented at the meeting. Results: Of 48 pts, 40 had WD/DD confirmed on pathology and were included; 2 had only WD LPS. Median age was 58 (48-65). Male/female ratio was 22/18. Nineteen pts received neoadjuvant CT (Group 1); 15 received CT for recurrent disease after upfront surgery (Group 2) and 6 received CT only (group 3). Based on the radiology report, response to first-line CT was: partial response (PR) 15/40, stable disease (SD) 19/40 and progression (PD) 6/40. Majority (36) received combination CT, mostly doxorubicin (A)-ifosfamide (I) (RR by CT regimen summarized in Table 1). In Group 1, 15/19 recurred after a follow-up of 30.4 months (m) (15.6-42). In groups 2 and 3, progression-free survival after starting CT was 5.4 m (2.1-9.0). One/two-year survival was: Group 1 100%/79%; Group 2 100%/93%; Group 3 77%/39%. Median survival was 50.5 m (29-194) for all patients. Conclusions: Combination CT yields a RR of 37% in WD/DD LPS. Analysis of the imaging characteristics will help us better understand response patterns in relation to RECIST. Response to CT in WD/DD LPS. First line Second line PR SD PD PR SD PD A 0 3 0 0 0 0 A+I 15 13 3 0 1 0 A+DTIC 0 2 2 0 0 1 Gemcitabine 0 0 1 1 0 0 Gemcitabine+Docetaxel 0 1 0 3 0 7 DTIC 0 0 0 0 0 1 I 0 0 0 1 0 0 Trabectedin 0 0 0 0 1 0
Utilization of adjuvant trastuzumab for T1a,b N0 HER2+ breast cancer in Ontario.
Authors: Andrea Eisen, Lyndee Yeung, Scott Gavura, Zachary M Brown, Maureen E. Trudeau
Journal: Journal of Clinical Oncology (2014)

e11569 Background: Less is known about the benefits vs risks of adjuvant H in women with small (<1 cm) node negative, Her 2+ BC vs. women with T> 1cm as the former were largely excluded from randomized trials. Ontario (population 13.5 million) has a publicly funded cancer care system; adjuvant H has been used available since 2005 for women with Her2+ BC if T> 1 cm or N+. In 2011 H became available for women with T1a,b N0 Her 2+ BC as part of an evidence building program. Baseline and outcomes data for this group are being prospectively collected to determine clinical benefit and toxicity and to guide future funding decisions. Methods: Subjects are enrolled prospectively by treating oncologist. Treatment is open-label and consists of H x 1 yr with an approved chemo regimen. Baseline data include demographics, stage, LVEF. Subjects will be followed for 10 yrs. Outcomes will include febrile neutropenia on chemo, changes in cardiac function and DFS. Results: Between May 2011 and March 2013, 137 women were enrolled. Conclusions: This is a large prospective cohort of subjects with T1a,b N0 Her2+ BC treated with chemo plus H x 1 yr. 38% of subjects were >60 y of age, 55% were ER+, and 35% had T1a disease, suggesting that oncologists consider Her2+ status an important predictor of recurrence. Subjects with other high risk features received more aggressive treatment. Characteristics Chemotherapy group AC/CMF (n=20) TC (n=80) DD-AC taxol/FEC-T (n=37) No. (%) No. (%) No. (%) Age at diagnosis (y) <40 2 (10.0) 4 (5.0) 1 (2.7) 41-50 0 (0.0) 20 (25.0) 11 (29.7) 51-60 7 (35.0) 27 (33.8) 13 (35.1) 61-70 11 (55.0) 23 (28.8) 11 (29.7) >70 0 (0.0) 6 (7.5) 1 (2.7) Tumour size (cm) <0.5 6 (30.0) 37 (46.3) 6 (16.2) 0.5-1.0 14 (70.0) 43 (53.8) 31 (83.8) Tumour grade 1 0 (0.0) 2 (2.5) 0 (0.0) 2 12 (60.0) 49 (61.3) 15 (40.5) 3 8 (40.0) 25 (31.3) 22 (59.5) Unreported 0 (0.0) 4 (5.0) 0 (0.0) Multifocal Yes 3 (15.0) 32 (40.0) 17 (45.9) No 17 (85.0) 48 (60.0) 20 (54.1) ER/PR status ER+/PR+ 4 (20.0) 21 (26.3) 16 (43.2) ER+/PR- 8 (40.0) 19 (23.8) 7 (18.9) ER-/PR+ 1 (5.0) 4 (5.0) 1 (2.7) ER-/PR- 7 (35.0) 36 (45.0) 13 (35.1) LVI Yes 0 (0.0) 9 (11.3) 5 (13.5) No 20 (100.0) 70 (87.5) 32 (86.5) Indeterminate 0 (0.0) 1 (1.3) 0 (0.0) LVEF baseline (%) >55% 18 (90.0) 80 (100.0) 36 (97.3) <55% 2 (10.0) 0 (0.0) 1 (2.7)
Patterns of palliative radiation near the end of life: A single-institution retrospective analysis.
Authors: Sara R. Alcorn, Thomas J. Smith, Todd R. McNutt, M. Jennifer Cheng, Sydney Morss Dy, Russell K. Hales, Theodore L. DeWeese, Susannah G. Ellsworth
Journal: Journal of Clinical Oncology (2013)

9636 Background: The care of patients who receive radiation therapy (RT) at the end of life (EOL) is under scrutiny to ensure effectiveness and value, with many patients not completing RT (Gripp, 2010; Toole, 2012). This retrospective analysis seeks to describe patterns of utilization of palliative RT, including rates of completion of RT offered at the EOL and the use of single fraction RT for bone metastases. Methods: Electronic medical records were used to create a database of 3,383 RT plans for brain, bone, lung, and other metastatic sites in patients treated at Johns Hopkins Hospital from 9/1/2007-7/15/2012. RT plans without palliative intent were excluded. T-tests and logistic regression compared patient and treatment characteristics between patients who died &gt; 1 month versus ≤ 1 month after their last RT fraction. Results: A total of 983 patients were treated to 1,524 sites, with an average of 1.7 RT sites (SD 1.3) per patient. Of these, 872 (89%) patients had complete records and were included in analysis. At the time of analysis, 85% had died. The mean age of 62.1 years (SD 3.4) did not differ statistically based on time from RT to death. Death ≤ 1 month after RT was documented in 215 (24.7%) patients. Compared to patients living &gt; 1 month after RT, patients receiving RT within the last month of life were more likely to be lung (17% versus 9%), less likely to be brain (34% versus 44%), and equally likely to be bone (45% versus 43%) sites. Patients who died ≤ 1 month after completing RT spent on average 5 days (16.6%) of the last month of life receiving RT, with no significant difference by disease site. Conclusions: Most patients receiving palliative RT finish therapy, with 25% dying ≤ 1 month after RT. Single fraction bone RT was relatively uncommon, with no significant difference in the rates of single fraction RT based on time from RT to death. These data provide a framework to match treatment patterns with national guidelines. Additionally, they provide context to model risk of death shortly after RT, which can aid in clinical decision-making. [Table: see text]
Effect of geographic distance from a cancer centre on choice of systemic therapy in metastatic colorectal cancer
Authors: M. D. Seal, G. R. Pond, T. Wilkieson, S. J. Hotte
Journal: Journal of Clinical Oncology (2009)

e17559 Background: There is little data on whether geographic distance from patient residence to a treatment facility is a predictor of systemic therapy utilization or clinical trial (CT) enrollment. Therefore a retrospective chart review was undertaken to investigate this variable. Methods: Consecutive patients with metastatic colorectal cancer (mCRC) assessed by a medical oncologist at the Juravinski Cancer Centre (JCC), Ontario during 2006 were selected. Patients with pathology other than adenocarcinoma and those with complete surgical resection of metastases were excluded. Distance and time to JCC were calculated using online mapping software. The study received full ethics approval. Results: 276 patients were included with full data available on 169 patients. Median travel time and distance to JCC were 23.0 minutes (min) and 19.2 kilometers (km), respectively. The maximum travel time was 120 min and 87% of patients lived within 60 min of JCC. Distance and time were highly correlated (p&lt;0.0001). Overall, 43% of patients had discussed a CT with their oncologist and 20% enrolled in a CT. Patients living &gt;50 km from JCC were less likely to discuss a CT (38%) or participate in a CT (15%) than patients who lived 25–50 km (39% and 19%) or &lt;25 km (47% and 23%) from JCC. These trends did not attain statistical significance (odds ratio [OR] = 0.88, 95% CI = 0.66–1.17, p = 0.39 for CT discussion, OR = 0.76, 95% CI = 0.54–1.08, p = 0.13 for CT enrollment). Distance was not a statistically significant (p = 0.42) predictor of number of treatment regimens, however, 44% of patients &lt;25 km from JCC received 3 or more lines of treatment compared with 33% of patients ≥25 km away. No association with survival was observed. Conclusions: Patients with mCRC living ≥25 km from JCC received fewer systemic regimens and were less likely to discuss or enter a CT. These trends were not statistically significant. Data collection is ongoing to increase the power of this study. No significant financial relationships to disclose.
A pilot study of raltegravir and cisplatin in head and neck squamous cell carcinoma (HNSCC).
Authors: Julie E. Bauman, Garth T Olson, Michael Spafford, Michael Nuara, Sagus Sampath, Sang-Joon Lee, Elizabeth A. Williamson, Yuehan Wu, Larry A. Sklar, Tudor I. Oprea, Robert Hromas
Journal: Journal of Clinical Oncology (2012)

TPS5602 Background: Metnase is a recently characterized DNA repair component present in anthropoid primates. Metnase, the fusion of a SET histone methylase domain and a Transposase nuclease (Tn) domain, enhances DNA double-stranded break (DSB) repair. The Tn domain trims free DNA ends for optimal end-joining, and is required to re-start stalled replication forks. The SET domain di-methylates H3K36 at the DSB, recruiting non-homologous end-joining repair components. Cisplatin (CDDP), the central chemotherapy in HNSCC, covalently binds DNA leading to intra- and interstrand crosslinks (ICL). In addition to blocking strand transcription and segregation, the ICL stalls DNA replication fork progression leading to collapse and DSB. The role of Metnase in DNA repair, including overcoming the stalled replication fork, makes it a potential therapeutic target. We hypothesize that Metnase inhibition may be a useful adjunct to CDDP. 3D modeling of the Metnase Tn domain identified significant homology with human immunodeficiency virus 1 (HIV-1) integrase. A virtual screen of the Chem Div library identified the HIV-1 integrase inhibitor, raltegravir, as a lead compound for inhibiting the Metnase Tn domain. We designed a pilot study in HNSCC to evaluate potentiation of CDDP DNA damage by raltegravir. Methods: The primary objective of this window-of-opportunity study is to analyze biomarkers of DNA damage, fork arrest, and apoptosis in serial tumor biopsies from patients (pts) with HNSCC undergoing CDDP, with and without raltegravir. Eligible pts: 1) have HNSCC with tumor site amenable to repeat, awake biopsy; 2) are appropriate candidates for CDDP. Pts are treated with 2 doses of CDDP 30 mg/m 2 . One CDDP dose is administered with raltegravir 400 mg bid for 5 days, starting the day before CDDP. Pts undergo 3 research biopsies, at baseline and 48-72 hours after each CDDP. Serial biopsies will be evaluated for expression changes in γH2AX, Annexin V, pChk1, pChk2, and p53BP1 by immunohistochemistry. Numerical increase in biomarker expression in tumors exposed to CDDP-raltegravir vs. CDDP will justify development of a phase I/II study. Four of 12 pts have enrolled and completed all biopsies. Supported by a grant from the American Cancer Society.
Randomized single institute pilot study of vaccinia-CEA(6D)-tricom and fowlpox-CEA (6D)-tricom with GM-CSF (V) in combination with docetaxel (D) in patients with colorectal cancer (CC)
Authors: A. R. He, J. Hwang, S. Malik, S. Park, J. Schlom, J. Marshall
Journal: Journal of Clinical Oncology (2006)

13538 Background: Our previous study demonstrated 40% patients with CC achieved stable disease at 4 months with V (JCO, 23(4):720–31, 2005.). Preclinical studies showed taxene enhanced tumor vaccine in delaying tumor growth and increasing the antigen-specific T cells. We report the results of a Randomized phase II pilot study of V in combination with docetaxel (D) in CC patients. Methods: 27 patients with metastatic CC were randomly assigned to 3 arms, stratified for HLA-A2. All patients received a ‘prime’ dose of vaccinia-Tricom on Day 0, followed by ‘boost’ doses of fowlpox-Tricom on Days 21 and q 21 days for 4 months; all vaccinations were followed by local GM-CSF (100 μg) for 4 days. Arm 1 received V; Arm II and III received V and D on D1, D8 during each fowlpox vaccination at 10mg/m 2 and 30mg/m 2 , respectively. Patients with stable disease continued vaccinations monthly after study completed. Safety data was evaluated. Primary endpoints included the impact of varying doses of D on CEA-specific T cell immune responses (CTL) using the ELISPOT assay, the recommended dose for further study as defined by the best immune response with acceptable toxicity, and objective clinical response. Results: The most common AE related to the vaccines was grade (g) 1 injection site reactions. Other common AEs were g1 fatigue, nausea, vomiting, fever, headache, and myalgia. There were 1 g3 fever and 1 g3 abdominal pain. The AE from the combination arm were contributed by D as expected, included g3: hyperglycemia (1), fatigue (1), elevation of liver function tests (2), pulmonary infection (1), abdominal pain (1), vomiting (1) or diarrhea (1). 6/ 27 patients have died 17 months after starting V. Patients received 2 to 12 cycles of therapy before disease progression. Observed clinical benefit was significantly lower than the 40% previously documented with V alone. The immune data is to be presented. Conclusions: Inferior clinical benefit as compared to our previous experiment could be explained by more heavily pretreated patients in this trial or negative impact of D on V. CTL data should explain this observation. No significant financial relationships to disclose.
Phase 2 trial of <sup>177</sup>Lutetium (<sup>177</sup>Lu) radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody (mAb) J591 (<sup>177</sup>Lu-J591) in patients (pts) with metastatic androgen-independent prostate cancer (AIPC)
Authors: M. J. Morris, M. I. Milowsky, N. Pandit-Taskar, C. Divgi, K. A. David, C. P. Rozario, S. Vallabhajosula, S. J. Goldsmith, H. I. Scher, D. M. Nanus
Journal: Journal of Clinical Oncology (2006)

4613 Background: J591 is an anti-PSMA mAb targeting the extracellular domain of PSMA, a highly PC restricted glycoprotein. 177 Lu linked to J591 via a DOTA chelate was evaluated in a phase 1 trial in pts with metastatic AIPC demonstrating acceptable toxicity (MTD = 70 mCi/m 2 ), excellent targeting of metastatic sites and biologic activity. Methods: Pts with progressive metastatic AIPC receive a single dose of 177 Lu -J591 in two cohorts (65 and 70 mCi/m 2 ). Cohort 1: 15 pts; Cohort 2: 17 pts. The primary endpoint is PSA and measurable disease response assessed at wk 12. Secondary endpoint is to evaluate toxicity. One 177 Lu imaging study is done at 1 week post-treatment to confirm tumor targeting. Results: 14 pts, median age 73 (5 chemo-naïve), have been treated on this ongoing 2-center study. One pt with bone-only metastases achieved an 87% decline in PSA by day 85 with resolution of bone pain. Bone scan at wk 12 revealed a flare response. As of day 222, the pt has not required additional therapy. PSA stabilization (&lt; 25% PSA rise above baseline) has been seen in 4 pts lasting 16 wks in 2 pts, 18 wks (1 pt) and 23 wks (1 pt), respectively. One pt withdrew at wk 56 without PSA progression. Of 5 pts with measurable disease, no objective responses were seen. Grade 3 and 4 thrombocytopenia occurred in 6 and 4 pts, respectively. 12/14 pts recovered plt counts to ≥ 150 x 10 9 /L (median time to recovery = 22 d). Grade 3 and 4 neutropenia occurred in 7 and 1 pts, respectively. 13/14 pts had ANC recovery to ≥ 2 x 10 9 /L (median time to recovery = 13 d). No significant drug-related non-hematologic toxicity has occurred. Excellent targeting of known sites of PC metastases has been observed in all pts. Conclusions: 177 Lu-J591 demonstrates anti-tumor activity in pts with AIPC with one pt achieving the primary endpoint (≥ 50% PSA decline) and 4 pts with PSA stabilization at a dose of 65 mCi/m 2 . Support: NIH CA102544 , NCRR M01RR00047, DOD PC031175 , David H. Koch Foundation, Cancer Research Institute, MSKCC Experimental Therapeutics Ctr, McCoey Fund, BZL Biologics, Inc. and Millennium Pharmaceuticals, Inc. No significant financial relationships to disclose.
Budget impact analysis of sargramostim use in patients with chemotherapy-induced neutropenia
Authors: M. Duh, E. L. Toy, C. L. Porter, P. L. Books, F. Vekeman, V. Barghout, A. T. Skarin
Journal: Journal of Clinical Oncology (2009)

e20596 Background: Myeloid growth factors are used to treat and prevent chemotherapy-induced neutropenia (CIN). Filgrastim and its long-acting version pegfilgrastim are granulocyte colony-stimulating factors (G-CSF), whereas sargramostim is a dual granulocyte- macrophage colony-stimulating factor (GM-CSF). This study analyzed the budget impact of substituting GM-CSF for G-CSF in the management of CIN from the perspective of a US health plan. Methods: A spreadsheet model was developed to compute annual and per-member-per-month (PMPM) costs associated with CSFs. Inputs included cancer prevalence, the proportion of patients receiving chemotherapy and G/GM-CSFs, incidence and cost of relevant adverse events (e.g., bone pain), and G/GM-CSF drug acquisition and administration costs. Incidence and cost of infection- and febrile neutropenia-related hospitalizations, based on recent analysis of medical insurance claims data, were also used. Cost savings (2006 USD) were assessed for utilization share switches from G-CSF to GM-CSF. Results: For a health plan with 1 million members, an estimated 976 patients received G/GM-CSF annually. Increasing baseline utilization shares for pegfilgrastim, filgrastim, and sargramostim of 70/30/0%, respectively, to alternative shares of 50/25/25% yielded substantial cost savings (see Table ), primarily related to G/GM-CSF acquisition and administration costs. Savings for patients switching from pegfilgrastim were greater than for patients switching from filgrastim. Results were sensitive to assumptions for drug cost and frequency of administration, but cost savings were observed for most scenarios. Conclusions: This study suggests that health plans can realize substantial cost savings by substituting sargramostim for filgrastim and pegfilgrastim in CIN patients. With 25% of sargramostim substitution, the cost saving could reach ≈$2 million for a health plan with 1 million members, or a saving of 16 cents per member per month. [Table: see text] [Table: see text]
Outcomes of patients (pts) with renal cell carcinoma and sarcomatoid dedifferentiation (sRCC) treated with nephrectomy (Nx) and systemic therapies (T) over three decades: The MD Anderson Cancer Center (MDACC) experience.
Authors: Sarp K. Keskin, Pavlos Msaouel, Kenneth R. Hess, Surena F. Matin, Eric Jonasch, Christopher G. Wood, Jose A. Karam, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2017)

534 Background: Pts with sRCC historically have had a poor prognosis. We determined the overall survival (OS) and prognostic factors of pts treated with Nx and T in the cytokine and targeted therapy eras. Methods: This is a retrospective study of pts with sRCC who had Nx and received T at MDACC in the cytokine era (1987-2005) or the targeted therapy era (2006-2015). OS was measured from time of diagnosis until death of any cause or last follow-up. OS times were estimated by Kaplan-Meier plots and were compared using the log-rank test. Cox regression models were used to determine the association of covariables with OS. Results: Among 199 pts with sRCC (80.9% clear-cell) identified, 167 pts (83.9%) have died at a median follow-up of 8.8 years (median OS 16.5 months; 95% CI: 15.2, 20.9). The 1-year, 2-year, and 5-year OS rates were 67%, 38%, and 14%, respectively. There was no significant difference in OS between pts with clear-cell vs. those with non-clear cell histology. Pts with metastatic disease at initial diagnosis had a significantly shorter OS compared with pts with localized disease (median 12.1 months vs. 23.3 months; p=0.0064). Biopsy of the primary tumor or a metastatic site was able to detect the presence of sarcomatoid features in only 7% of cases. The % of sarcomatoid component (&lt;10%, 10-40%, &gt;40%) in the primary tumor did not impact OS. For first-line (1L) therapy, 77 pts (39%) received targeted agents, and 122 pts (61%) received chemotherapy or cytokines. Although a significant improvement in OS rate was observed at 1 year for pts treated in the targeted therapy era (p = 0.011), this effect was attenuated at year 2 and disappeared at years 3-5 after diagnosis. Conclusions: Pts with sRCC still have poor prognosis with no clear long-term benefit of targeted therapy, underscoring the need to develop more effective systemic therapies for these patients.