tbuckley/cabot-search huggingface dataset:
Double-blind, randomized trial of granulocyte-colony stimulating factor (GCSF) versus (v.) placebo during postoperative radiation (RT) for advanced resectable squamous cell head and neck cancer (SCCHN): Impact on mucositis
Authors: Y. B. Su, A. Vickers, M. J. Zelefsky, D. H. Kraus, A. R. Shaha, J. P. Shah, S. Lake, L. B. Harrison, G. J. Bosl, D. G. Pfister
Journal: Journal of Clinical Oncology (2004)

5587 Background: Mucositis is common in patients (pts) with SCCHN receiving RT, contributing to the need for tube feeds (PEG) and treatment delays. GCSF has decreased mucositis in pts receiving chemotherapy (CT). We evaluated its ability to decrease mucositis and related dysfunction during postoperative RT using a randomized, placebo-controlled design. Methods: Eligible pts had completely resected, stage II-IV SCCHN, no prior RT or CT, and signed informed consent. Pts were stratified by primary site, then randomized to receive GCSF 3 mcg/kg or placebo daily by subcutaneous injection during RT (63 Gy, 1.8 Gy/day). Pts and treating physicians were blinded to treatment assignment. Endpoints: need for PEG feeds (primary), severity of mucositis/level of intervention for mucositis (secondary; both scored biweekly, grades 0–3). Results: 41 pts (132 planned) were enrolled at MSKCC from 1/92 to 12/96. Study was closed due to slow accrual. Pt characteristics (GCSF v. placebo): median age 59 v. 54; pathologic stages: T3/4 32 v. 50%, N2/3 68 v. 59%, Stage IV 79 v. 68%. Primary site distribution was comparable between groups. All pts Karnofsky ≥ 80. Mean absolute neutrophil count during RT 24.1 v. 4.1 x109/L (p<0.0001). 9 pts treated with GCSF required dose reduction (white blood count ≥ 40 x109/L, radiotherapist blinded), 2 pts had grade 2/3 bone pain, 3 pts total refused injection (2 GCSF, 1 placebo). 39 pts were evaluable. All received 63 Gy. Outcomes (GCSF v. placebo): PEG rate 0 v. 10% (p=0.16), RT interruption 0 v. 10% (p=0.16), mean mucositis grade 0.84 v. 1.11 (p=0.11), mean level intervention 0.59 v. 0.95 (p=0.076), mean # of treatment days 35.9 v. 38.1 (p=0.007). 5-year actuarial survival (intent to treat, 41 pts, median followup 7.6 years) was 79 v. 47% (p=0.062, log rank test). Conclusions: GCSF during RT was feasible, led to trends for less PEG feeds and mucositis (underpowered), significantly less # of treatment days, and no decrement in survival. Survival data are not clearly explained by known prognostic factors, and warrant further study. No significant financial relationships to disclose.
Current imaging techniques to detect brain metastasis and its findings in correlation with histopathological diagnosis in african american population with lung cancer
Authors: M. Kalavar, S. G. Naik, H. Chenthilmurugan, S. Kodali, A. Agheli, A. Sangal, T. Dumlao, Z. He, C. Rathnasabapathy
Journal: Journal of Clinical Oncology (2008)

19107 Background: To assess the incidence of brain metastasis in lung cancer with current imaging techniques, in correlation with their respective histopathologic diagnosis in african americans. Methods: Retrospective analysis of 69 african american patients with histopathologic diagnosis of lung cancer between January 2005 and December 2007 with appropriate metastatic workup were done. Results: We reviewed the data of 69 african american patients with lung cancer, and were found to have the following histological pattern. Adenocarcinoma is the commonest histological type with 34.8%(n=24), followed by 18.8%(n=13) squamous cell carcinoma, 5.8% (n=4) small cell carcinoma, 5.8% (n=4) large cell neuroendocrine carcinoma, 5.8%(n=4) poorly differentiated carcinoma, 2.9% (n=2) sarcoma, 1.44% (n=1) bronchoalveolar carcinoma and 24.6% (n=17) NSCLC(unspecified histology). Brain metastasis were found in a total of 9 patients. CT head with contrast and MRI showed multiple brain metastasis in 10.14%(n=7) and 13.04%(n=9) respectively. Among the histological types mentioned above,3 (75%) patients with poorly differentiated lung cancer, 2 (50%) patients with small cell carcinoma, 1 (25%) patient with large cell neuroendocrine tumor and 3(12.5%)patients with adenocarcinoma had brain metastasis. Conclusion: Brain metastasis were found increasingly in poorly differentiated carcinoma in patients lung cancer in african americans. Brain imaging may be considered as a part of routine staging workup for histopathologies other than small cell lung cancer. Larger studies are needed to validate these results. Frequency of brain metastasis in african Americans according to histology. Histology Adenocarcinoma Poorly differentiated small cell Large cell neuro endocrine Total no. of patients 24 4 4 4 No. of patients with brain mets 3 (12.5%) 3 (75%) 2 (50%) 1(25%) No significant financial relationships to disclose.
Characteristics of colorectal cancer in patients younger than 40 years compared to older patients.
Authors: Mohamed E. Salem, Monica Arun, Greg Dyson, Chadi Saad, Cassra Arbabi, Tania Jain, Stephanie Taylor, Sara Kunz, Minsig Choi, Anthony Frank Shields, Philip Agop Philip
Journal: Journal of Clinical Oncology (2013)

371 Background: The incidence of colorectal cancer (CRC) in younger patients (pts) is increasing. There is limited data on tumor characteristics and treatment outcome in this population. Methods: Patients with CRC treated at the Karmanos Cancer Center from 2005 to 2011 were studied. Younger (≤40 years) and older (&gt;40 years) groups from a predominantly inner city population were compared for patient and tumor characteristics, treatment patterns, and survivals. T-tests and Fisher’s exact tests were used to determine statistical differences between age groups while the Kaplan-Meier method was used to estimate survival. Results: 42 pts were ≤ 40 (range, 17-40 years) and 96 pts were &gt; 40 (range, 42-88 years). Mean ages for the groups were 33 and 60 years, respectively. There was no statistically significant difference in the distribution of race, gender, stage or KRAS mutation status between the two groups; however, older pts had a higher mean body mass index compared to younger pts (28 versus 23, p&lt;0.001). Older pts were more likely to have a right colon primary (OR = 7.5, p = 0.04), while younger pts had higher likelihood of having sigmoid primary (OR = 3.4, p = 0.002) and worse grade (poorly differentiated) tumors (OR = 8.3, p &lt;0.001). There were no significant differences between metastatic status or sites of metastases between the two groups. Significantly more young pts underwent surgery than older pts (92% versus 62%, p = 0.005). FOLFOX plus bevacizumab was the most commonly used first line treatment for both groups. The median survival estimates were 16.9 (8.1-23.9) and 17.1 months (13.3-31.0) for the younger and older pts, respectively. Importantly, the one-year survival rates were similar for both groups: 41% for both (p = 1). On the multivariate analysis, whether pts had a primary in the right or sigmoid colon was the only independent predictor of survival. Conclusions: Younger pts with colon cancer were diagnosed at a similar stage of the disease as older pts, but more likely to have poorly differentiated tumors. Younger pts were more likely to receive surgical interventions; however, both groups had equivalent one-year survivals. These results support the need for further prospective investigation in a larger population.
The germline mutaion pattern of CDH1 gene in 12 Chinese hereditary diffuse gastric cancer kindred
Authors: H. Wang, J. Ren, Y. Zhang, R. Huang, L. Zhang
Journal: Journal of Clinical Oncology (2005)

9548 Background: E-cadherin is responsible for the cell-cell adhesion. Germline mutations in E-cadherin gene (CDH1) was firstly recognized in Maori kindred with hereditary gastric cancer(HGC) in New Zealand by Guilford. The similar changes had been described in European and African-American families in recently years, but the statues was not clearly in Chinese, which have a high gastric cancer incidence. The research was aimed to analyze the mutation statues of E-cadherin gene in 12 Chinese HGC families and to evaluate its role in the disease. Methods: HGC kindred were strictly selected followed 1994 Seoul Standards. All 16 exon of CDH1 were amplified by PCR from the lymphocyte genomic DNA, every amplicom was screened by denaturing high performance liquid chromatography and mutation was confirmed by direct sequencing. Results: Four germline changes were found in 5 of 12 families. In addition to 1 previously described polymorphisms site and a missense mutation, 2 novel stop code mutations had not been reported. A stop code mutation (CAG-TAG, Gln152***, exon 4) was present in 3 members (1 gastric cancer patient, 27 years old, the patient’s son and the patient’s young brother) in one family. The other stop code mutation (TAT-TAG, Tyr523***, exon 11) was present in a 39 years old patient and 2 of his families. Other two families shared the same previously reported missense mutation (AAC-AAG, Asn751Lys, exon 14), which presented in 6 and 4 members respectively, 2 of them had gastric cancer (44 and 35 years old). Conclusions: Three important germline mutations were found in 16 members of 4 families, 4 of them were young HGC patients, which indicates that members with these mutations appears to have a tendency to early onset gastric cancer. CDH1 germline mutation can also be detected in Chinese HGC and may be a valuable marker for HGC prevention. No significant financial relationships to disclose.
Addition of low-dose, involved-field external beam radiotherapy just prior to radioimmunotherapy for CD20+ lymphoma: “Priming” cell death pathways?
Authors: M. B. Tomblyn
Journal: Journal of Clinical Oncology (2011)

e18533 Background: Radioimmunotherapy is an effective and increasingly used option for patients with B-cell lymphomas. Particularly in the relapsed/refractory setting, patients may have sizable disease limited to one or a few sites. Many patients are heavily pretreated, with a subsequent downregulation of CD20 expression on the surface of lymphoma cells. Emerging evidence suggests a role for radiation to upregulate CD20 expression, which could sensitize the irradiated lymphoma cells to radioimmunotherapy. Methods: Between July 1, 2009, and December 31, 2010, we treated 13 patients with a combination of low-dose, involved-field radiotherapy (IFRT) and radioimmunotherapy (RIT) for relapsed/refractory B-cell lymphoma: 5 transformed, 4 follicular, 2 marginal zone, 1 CLL/SLL, and 1 lymphoplasmacytic. All received 4 Gy in 2 fractions IFRT to sites of active disease, 2.5 cm or larger. 131I-tositumomab was used in 8 patients and 90Y-ibritumomab tiuxetan in 5 patients. The median age of patients treated was 61 (38 – 82). The median size of persistent disease prior to treatment was 4.2 cm (2.5 – 19.5). Results: With a median follow-up of 14 months (6 – 21), 11/13 patients obtained a complete response to combined therapy and remain in remission at this time. No patients have failed within the IFRT fields. Two patients achieved a local CR but exhibited persistent disease outside the IFRT fields. All 13 patients tolerated combined IFRT and RIT very well with no toxicity from the addition of IFRT, and only transient grade 2-3 hematologic toxicity from the RIT. The progression-free survival (PFS) is 100% in patients achieving a CR and is 85% for all patients treated. Conclusions: The addition of IFRT to sites of active disease > 2.5 cm to RIT in patients with relapsed/refractory B-cell lymphomas is well-tolerated, adds no toxicity to that of RIT alone, and results in excellent PFS, particularly for patients who obtain a CR. As the only failures to therapy were outside of radiation portals, the addition of IFRT to sites of active disease may play an important role in improving PFS when added to RIT. Prospective studies are needed to further evaluate this novel combined therapeutic approach.
Toxicity in a multimodality approach of radical prostatectomy with radiation and hormonal therapy.
Authors: Stacy Loeb, Meike Adam, Pierre Tennstedt, Wolfgang Huber, Juergen Bernard, Derya Tilki, Markus Graefen, Hartwig Huland, Thorsten Schlomm
Journal: Journal of Clinical Oncology (2016)

107 Background: While the optimal use and timing of secondary therapy after radical prostatectomy remain controversial, there are limited data on the patient-reported outcomes following multimodality therapy. Our objective was to assess the impact of additional radiation and/or hormonal therapy on long-term urinary continence, quality of life and potency after radical prostatectomy. Methods: Among 13150 men treated by radical prostatectomy (RP) from 1992-2013, 905 underwent secondary radiation therapy (RP+RT), 407 received androgen deprivation therapy (RP+ADT) and 688 a combination of RT and ADT (RP+RT+ADT). Urinary function, sexual function and quality of life were evaluated annually using self-administrated validated questionnaires. Urinary function was assessed by the use of the number of pads in 24h (analyzed as 0 pads, safety only, 1-2, or ≥ 3 pads). Potency was defined as ≥ 3 points out of 5 on the question whether erections were hard enough for penetration. Quality of life was assessed using a score from 0-100%.The distribution of urinary function, sexual function and quality of life were plotted as a function of time after bootstrap analysis (n = 1000) of a propensity score matched cohort. Results: Urinary function. The distribution of 0 pads and 1 safety pad between patients with a) RP and RP+RT was 72.3% vs. 67.9% and 16.7% vs. 18.6%; b) between RP and RP+HT was 64.5% vs. 55.5% and 16.1% vs. 21.9%; c) between RP and RP+RT+ADT was 67.4% vs. 54.8% and 17.7% vs. 21.8% and d) between RP+RT and RP+RT+ADT was 64.5% vs. 55.5% and 16.1% vs. 21.9%. Potency. The distribution of potency between patients with a) RP and RP+RT was 62.9% vs. 40.0%; b) between RP and RP+HT was 59.1% vs. 29.3%; c) between RP and RP+RT+ADT was 57.4% vs. 24.0% and d) between RP+RT and RP+RT+ADT was 44.2% vs. 32.1%. Quality of life. The distribution of a score of 83.3%-100% between patients with a) RP and RP+RT was 67.9% vs. 57.4%; b) between RP and RP+HT was 57.8% vs. 41.7%; c) between RP and RP+RT+ADT was 59.3% vs. 48.2% and d) between RP+RT and RP+RT+ADT was 60.0% vs. 41.2%. Conclusions: Secondary therapy after radical prostatectomy has a negative influence on urinary function, potency and quality of life.
Outcomes of advanced urothelial carcinoma following discontinuation of programmed death (PD)-1 or PD-ligand (L)-1 inhibitors.
Authors: Guru Sonpavde, Gregory Russell Pond, Stephanie A. Mullane, Ana Arlene Ramirez, Nicholas J. Vogelzang, Andrea Necchi, Thomas Powles, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2016)

385 Background: The outcomes and therapy of advanced urothelial carcinoma (UC) patients (pts) following discontinuation of PD-1/PD-L1 inhibitors are unclear. We performed a retrospective analysis to examine the frequency of systemic therapy administered following PD-1/PD-L-1 inhibitors and outcomes in these pts. Methods: Data were collected from institutions for pts with advanced UC following prior PD-1/PD-L1 inhibitors as salvage therapy. Baseline demographics and therapy administered following prior check-point inhibitors was captured. Univariable Cox regression analyses examined clinical factors potentially associated with overall survival (OS) following check-point inhibitors. Results: Data from 62 pts were available from 4 institutions with capture of therapy and outcomes following checkpoint inhibitor immunotherapy. The median age was 65.5 years and 51 (82.3%) were male. The median duration of PD-1/PD-L1 inhibitors available from 55 pts was 64 days (range 7-669). Of these pts, 22 (35.5%) received post-PD1/PD-L1 pathway inhibitor therapy with a variety of chemotherapy (n = 16), chemobiologic combination (n = 1), biologic agents (n = 4) and immunotherapy (n = 1). The median time from last PD1/PD-L1 pathway inhibitor therapy to subsequent therapy was 58 days (range 14-242). The median OS of all pts following completion of PD-1/PD-L1 inhibitors was 149 days (95% CI: 75-359). Among pts who received some post-PD1/PD-L1 pathway inhibitor therapy, median OS was 182 days (95% CI: 121-372), and the median time to progression was 124 days (95% CI: 61-273) when examining from start of post-PD1/PD-L1 therapy. Among these 22 pts, the only significant baseline prognostic factor associated with OS was performance status. Conclusions: In this dataset, 35.5% of pts with advanced UC received subsequent systemic therapy following salvage therapy with PD1/PD-L1 inhibitors. Outcomes with subsequent therapy appear similar to historically observed outcomes in pts who had not received prior PD1/PD-L1 inhibitors. Further study of pts post-PD1/PD-L1 inhibitor therapy is warranted to identify factors associated with outcomes and potentially synergistic sequences.
Survival and toxicity following chemoradiation for carcinoma of the cervix: Impact of multiple phase treatment and shielding.
Authors: L. Bhatt, M. King, S. Pirrie, M. S. Anwar, A. El-Modir, I. N. Fernando
Journal: Journal of Clinical Oncology (2011)

e15506 Background: Concurrent chemoradiation is standard therapy for cervical cancer. At University Hospital Birmingham standard primary treatment consists of concurrent cisplatin with external beam radiotherapy (EBRT) at 45–50.4Gy in 25–28 fractions with or without a single medium-dose rate brachytherapy insertion of 25–27Gy to point A. Chemoradiation is also used for the post-operative treatment of high risk disease, with brachytherapy used for vaginal margin involvement. Between January 1999 and October 2006 multiphase treatment (EBRT volume reduced beyond 45Gy) and increased shielding of bowel and sacrum were introduced. We set out to establish outcomes and significant (grade 3-4) late toxicity (SLT) during this period, and to assess the impact of multiphase treatment and shielding. Methods: Retrospective review of case notes and radiotherapy planning films was used to obtain patient characteristics, EBRT dose by phase, number of shielded areas, and data related to overall and disease-free survival, local and distant recurrence, and late toxicity. Survival and progression-free survival was analysed using the Kaplan–Meier method and Log-rank test. Differences in SLT rates between groups were analysed using the Chi-squared and Fisher’s Exact tests. Results: 175 patients of median age 45 (22-76) were treated radically between 1999 and 2006. 74% received primary chemoradiation whilst 26% had post-operative treatment. 3 year survival for stages I, II and III disease were 89%, 76% and 51% respectively, with 3 year overall survival of 73.7% (95% CI 65.9-79.9) and 3 year progression-free survival of 71.6% (95% CI 63.3-78.4). Local pelvic failure was 9% and remained stable throughout the study period. Overall SLT rate was 13%, with lower rates for post-operative treatment than primary chemoradiation (4%v 16%, p=0.03). However with single phase treatment SLT was 29% versus 12% following multiphase EBRT, and 16% when <2 areas were shielded versus 6% with ≥3 shielded areas (p=0.01). Conclusions: Shielding and multiphase treatment not only reduce dose to organs at risk but can also reduce late toxicity without compromise of local control or survival.
Abstract 17711: The Combination of Dyssynchrony and Global Longitudinal Strain by 3D Speckle Tracking After ST-Elevation Myocardial Infarction is an Useful Predictor
Authors: Noriaki Iwahashi, Hironori Takahashi, Yasushi Matsuzawa, Nobuhiko Maejima, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Kazuo Kimura
Journal: Circulation (2016)

Background: Left ventricular (LV) global strain estimated immediately after ST elevation AMI (STEMI) was reported as a predictor of LV remodeling. Furthermore, LV dyssynchrony estimated by 2D strai...
Genomic characterization of HER2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy—results from the ACOSOG Z1041 (Alliance) trial
Authors: R. Lesurf, O.L. Griffith, M. Griffith, J. Hundal, L. Trani, M.A. Watson, R. Aft, M.J. Ellis, D. Ota, V.J. Suman, F. Meric-Bernstam, A.M. Leitch, J.C. Boughey, G. Unzeitig, A.U. Buzdar, K.K. Hunt, E.R. Mardis
Journal: Annals of Oncology (2017)
A phase II study of ENMD-2076 in platinum-resistant ovarian cancer.
Authors: U. Matulonis, W. P. Tew, D. Matei, K. Behbakht, G. F. Fleming, A. M. Oza
Journal: Journal of Clinical Oncology (2011)

5021 Background: ENMD-2076 is an oral small molecule kinase inhibitor with activity against Aurora kinases, VEGFRs, FGFRs and other kinases such as Src, c-kit and FAK, with a role in the pathogenesis of ovarian cancer. ENMD-2076 had activity in ovarian cancer patients who participated in the Phase 1 study. Methods: Single agent ENMD-2076 was given daily for recurrent ovarian, peritoneal or tubal cancer. Eligibility: Up to 3 prior lines of chemotherapy, ECOG PS 0 or 1, normal organ function and BP, and platinum resistant (disease progression within 6 months of most recent previous platinum-based regimen). Primary endpoints are progression free survival (PFS) rate at 6 months, toxicity (CTCAE v4) and pharmacodynamic evaluations. Results: 64 patients were enrolled. Median age is 57 years (range 20-80). Median performance status is 0. Number of treatment cycles to date is 171 (cycle=28 days), with a median of 2 cycles per patient (<1 to 10+ cycles). 25% had prior anti-angiogenics; 40% had prior liposomal doxorubicin. Median number of prior regimens is 2. Starting dose of ENMD-2076 was 325 mg/d (275 for BSA<1.65m2) but reduced to 275 mg/d (250 for BSA<1.65m2) after 23 patients due to toxicities and treatment delays. The most common related adverse events, all grades and Grade 3/4 included fatigue (55%/15%) and hypertension (53%/20%). Other Grade 3/4 toxicities included N/V/D and gastritis (n=5), reversible liver function tests (n=3), hand foot syndrome (n=2), thromboembolic events (n=3), cytopenias (n=2), subarachnoid hemorrhage (n=1), thyroiditis (n=1), decrease in LV function (n=1) and reversible posterior leukoencephalopathy syndrome (n=1). To date, 46 patients have had at least one post baseline assessment. There have been 3 PRs per RECIST v1.1 (7%) confirmed two months apart, and 27 patients with SD (59%) as their best response. 5 patients have received at least 6 months of therapy. Archival tissue is being evaluated for relationship of response to HIF1alpha, CD31, Ki67 and KDR. Conclusions: ENMD-2076 is active in platinum resistant recurrent ovarian cancer. Side effects are consistent with activity against Aurora A and KDR. Data on the correlative analyses and updated data on the study endpoints will be presented.