tbuckley/cabot-search huggingface dataset:
Effect of metastasectomy and doxorubicin dose on the outcome of patients with metastastic leiomyosarcoma: A multicenter study
Authors: N. Penel, A. Italiano, N. Isambert, E. Bompas, G. Bousquet, G. Bousquet, F. Duffaud
Journal: Journal of Clinical Oncology (2009)

10580 Background: The role of metastasectomy and front-line chemotherapy modalities remain debated in the metastastatic soft tissue sarcoma setting. Methods: Data from 147 M-LMS patients (1988–2008) reviewed in 6 French centers were retrospectively analyzed. Prognostic factors for progression-free and overall survivals (PFS and OS) were identified using log-rank tests and Cox multivariate analysis. The respective impact of treatment modalities on PFS and OS were assessed after adjustment to prognostic factors. Results: This database included 46 (31%) uterus and 101 soft-tissues (69%) M-LMS. All patients received doxorubicin as front-line regimen associated with ifosfamide in 78 cases (53%) or dacarbazine in 56 cases (38%). The planned dose of doxorubicin was &gt; 60 mg/m 2 /3 weeks in 24 patients (16%). After front-line chemotherapy, 36 patients with lung metastasis (24%) underwent subsequent complete metastasectomy. The median PFS was 6 months. The univariate analysis identified the following prognostic factors for PFS: performance status (PS), grade, presence of liver or lung metastases. But, the multivariate analysis did not retain independent prognostic factor for PFS. Only one treatment parameter was associated with better PFS: planned doxorubicin dose superior to 60 mg/m 2 /3 weeks (HR=7.57 [1.32–10.40], p=0.023). The median OS was 14 months (1–115). The univariate analysis identified the following prognostic factors: PS, time interval between diagnosis and metastatic relapse, local relapse and grade. Under multivariate analysis, there was only one good prognostic factor for PFS: interval time between initial diagnosis and metastasis &gt; 12 months (p=0.006). After adjustment to this factor, multivariate analysis shown that complete metastasectomy improved the PFS (HR=0.52, [0.38–0.87], p=0.012) and addition of ifosfamide was associated with worst outcome (HR=1.42 [1.05–2.10], p=0.028). Other chemotherapy parameters did not significantly modify OS. Conclusions: Doxorubicin dose and metastasectomy remain the cornerstone of the optimal treatment of M-LMS. Addition of Ifosfamide seemed to be associated with worst outcome. Dacarbazine seemed to have no significant impact. [Table: see text]
Clinicopathologic analysis of well, moderately and poorly differentiated gastroenteropancreatic neuroendocrine tumors
Authors: J. R. Strosberg, D. Coppola, A. Neumann, L. Kvols
Journal: Journal of Clinical Oncology (2007)

15028 Background: Pathologic features used to classify neuroendocrine tumors include mitotic rate, pleomorphism and Ki-67 index. Based on these criteria, neuroendocrine tumors are classified into well, moderately, and poorly-differentiated categories. But whereas this nomenclature is conventionally employed, it is not well defined in the field of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In particular, ‘moderately-differentiated‘ GEP-NETs are not formally recognized as a distinct category, and the clinical behavior of these tumors has not been described. Our classification of GEP-NETs is based on cell mophology and mitotic index, with well-diferentiated tumors displaying monomorphic appearance and rare mitoses (&lt;2/10HPF), poorly differentiated tumors consisting of pleomorphic cells with a high mitotic index (&gt;10/10HPF) and moderately-differentiated tumors displaying intermediate morphology and mitotic rate (2–10/10HPF). Methods: We performed an institutional chart analysis of patients with metastatic GEP-NETs, selecting all poorly and moderately differentiated cases and randomly selecting an equal number of patients with well differentiated tumors. The primary endpoint was overall survival. Results: A total of 83 cases were analyzed (28 well, 28 moderately, and 27 poorly differentiated). Overall survival correlated strongly with histological classification. At 2 years, survival rates among patients with well, moderately and poorly differentiated tumors were 100%, 57% and 22% respectively (p&lt;0.001). De-differentiation of tumors was associated with a decreased rate of pentetreotide scan positivity, decreased rates of neuroendocrine hormone secretion and more widespread organ metastases. Conclusions: The classification of GEP-NETs into three histologic categories (well, moderately and poorly differentiated) correlates strongly with survival. Other features of neuroendocrine tumors (such as secretion of hormones and expression of somatostatin receptors) also correlate with histological classification. ‘Moderately- differentiated‘ neuroendocrine tumors should be recognized as a subset of GET-NETs with a prognosis that is distinct from well and poorly differentiated tumors. No significant financial relationships to disclose.
ER alpha genotypes and breast cancer recurrence
Authors: J. L. Grabinski, G. Chisholm, L. S. Smith, R. L. Drengler, S. Kalter, G. Rodriguez, A. Garner, J. Cooper, B. Pollock, J. Kuhn
Journal: Journal of Clinical Oncology (2008)

501 Background: Pharmacogenomic studies have documented the importance of CYP2D6 in the metabolism of tamoxifen (TAM) and the resulting clinical outcomes. However, there is no data relating polymorphisms within the estrogen receptor to disease recurrence in patients receiving adjuvant TAM. Methods: Blood samples and clinical data were collected at baseline. Assessment of clinical data was conducted yearly to evaluate disease recurrence. A Taqman Allelic Discrimination assay was utilized for genotyping the ER alpha Pvu II polymorphism. Fisher's exact tests were used to test relationships of genotypes and disease recurrence. Cox regression analysis was used to assess time to disease recurrence and was adjusted for lymph node status, histologic grade, and tumor size. Results: Within our cohort of 301 women receiving adjuvant TAM therapy, 291 women were eligible for analysis. With a median follow-up time of 5.2 years, 5% have developed recurrent disease. Patients with the ER alpha Pvu II PP genotype had a higher risk of disease recurrence than patients with the Pp or pp genotype (OR=3.1; 95% CI 1.1 - 8.9; p=0.04). ER alpha approached statistical significance as a predictor of time to disease recurrence (HR 3.2; 95% CI 0.92 - 11.2; p=0.07). In the subpopulation of patients that were converted to an aromatase inhibitor, the PP genotype was associated with a significantly higher risk of disease recurrence, with a stronger association than in the overall cohort (OR=5.6; 95% CI 1.3 - 24.5; p=0.03). PP genotype and conversion to an aromatase inhibitor was a significant predictor of time to disease recurrence in this subpopulation (HR 12.0; 95% CI 1.7 - 83.5; p=0.01). Conclusions: Our data suggests that ER alpha PP genotype is associated with a higher risk of disease recurrence compared with Pp and pp genotypes and in a subpopulation of patients converted to an aromatase inhibitor, a shorter time to recurrence. Further investigation with a larger sample size is needed to confirm the impact of ER alpha polymorphisms on survival. No significant financial relationships to disclose.
Antitumor Activity of Pembrolizumab (Pembro; Mk-3475) and Correlation with Programmed Death Ligand 1 (Pd-L1) Expression in a Pooled Analysis of Patients (Pts) with Advanced Non–Small Cell Lung Carcinoma (Nsclc)
Authors: E.B. Garon, L. Gandhi, N. Rizvi, R. Hui, A.S. Balmanoukian, A. Patnaik, J.P. Eder, G.R. Blumenshein, C. Aggarwal, J-C. Soria, M.A. Ahn, M.A. Gubens, S.S. Ramalingam, E. Johnson, H. Arkenau, G.M. Lubiniecki, J. Zhang, R.Z. Rutledge, K. Emancipator, N. Leighl
Journal: Annals of Oncology (2014)
Is serum HER2-ECD testing significant for resectable gastric cancer?
Authors: Tsutomu Tanaka, Masahiro Tajika, Makoto Ishihara, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Hiroshi Imaoka, Mitsuyoshi Hashimoto, Yasushi Yatabe, Kei Muro, Kenji Yamao, Yasumasa Niwa
Journal: Journal of Clinical Oncology (2015)

48 Background: Accurate assessment of human epidermal growth factor receptor (HER) 2 is essential for patients with gastric cancer (GC) who may benefit from therapies targeting this surface receptor such as trastuzumab. The extracellular domain (ECD) of the HER2 protein may be shed into the serum and is detectable using an enzyme-linked immunosorbent assay. Correlations have been reported between raised baseline ECD levels, suggesting that serum ECD levels may be useful in making treatment decisions in patients with HER2 positive GC. We investigated this relationship in patients with resectable GC. Methods: This retrospective study was conducted in 71 patients with resectable GC between Apr. 2009 and May 2012. We assessed HER2 protein overexpression and gene amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 positive was defined as IHC 3+ or IHC 2+/ positive FISH. The serum HER2-ECD level was measured using the blood serum before the surgical treatment. We examined the relationship between serum HER2-ECD level, HER2 expression in resected specimens, depth of invasion of cancer, lymph node metastasis, and clinical stage. Results: Baseline values were available in 71 patients, and of these, 2 (2.8%) had raised levels (&gt; 15 ng/mL). Median serum ECD levels was 11.7 (7.5-17.9) ng/mL. Two patients showing high HER2-ECD without HER2 over-expression. No clear relationship was found between baseline ECD levels and HER2 over-expression. Serum HER2-ECD level was not associated with invasion depth and lymph node metastasis, and clinical stage. Conclusions: There is no significance of serum HER2-ECD testing in resectable gastric cancer.
Omission of post-tumorectomy radiation (RT) for patients treated for invasive breast cancer in Caribbean nations
Authors: G. S. Sidhu, D. Bristol, N. Palanisamy, T. Lewis, N. Patel, B. Adamson, A. S. Braverman
Journal: Journal of Clinical Oncology (2008)

11506 Background: Breast Cancer (BC) is an increasing problem in West Indies, where access to chemotherapy and radiation is limited. The East Flatbush section of Brooklyn, NY, where the Kings County Hospital Breast Cancer Clinic is located, has many West Indian immigrants. Methods: Since 1996, 67 patients diagnosed with and treated for localized BC in the West Indies came to the Clinic for a second opinion or further treatment. Their charts were retrospectively reviewed. Results: Of the 67 patients, 27 had mastectomies and 35 tumorectomies; 30 of the latter had not received radiation (T-RT). The intervals (months) between the dates of primary surgery and that of their presentation at our clinic for all 67 patients were a median of 8 (range 1–156, mean 19); for the 30 T-RT patients the intervals were a median of 4 months (range 1–48; mean 7). Local recurrence was found in 17 of the 30 T-RT patients (57%), and in 8 of the 32 patients who had mastectomies, or tumorectomy with radiation (25%). We were able to determine why 20 of the 30 T-RT patients had not received radiation. Four were referred to other nations for RT. Twelve denied having been offered RT, though we lack statements from their physicians. Four refused RT. Access to RT in these patients’ nations is known to have been limited or unavailable. That less time elapsed (≤4 months in most) between primary surgery and presentation at our clinic for the 30 T-RT patients than for those who had received complete local treatment, suggests that the former were aware of the need for further therapy, and came to our clinic as soon as travel arrangements were made. Conclusions: Eighty-five per cent of patients treated with tumorectomy for breast cancer in Caribbean nations had not received RT there. RT was therefore delayed for a median of 4 months after surgery, and 57% of these patients presented to our clinic with local recurrences. Tumorectomy for breast conservation in patients with invasive carcinoma may not be safe and practicable in regions lacking ready access to RT. No significant financial relationships to disclose.
Phase 2 study of weekly triplet regimen of docetaxel, carboplatin and gemcitabine in recurrent platinum-sensitive epithelial ovarian cancer
Authors: M. Salimichokami, A. A. Vahid, M. R. Mir
Journal: Journal of Clinical Oncology (2004)

5150 Background: To investigate the efficacy and toxicity of a triplet regimen of weekly Docetaxel, Carboplatin, and Gemcitabine in recurrent Platinum-sensitive epithelial ovarian cancer. Methods: 24 patients with recurrent Platinum-sensitive epithelial ovarian cancer were treated with a novel triplet regimen of weekly Docetaxel (25mg/m2) and weekly Carboplatin (AUC:2) and weekly Gemcitabine (600 mg/m2). Patients were evaluated for response by clinical,imaging and biochemical (CA 125) methods. Restin criteria was used for CA 125 response. Patients were treated from 2000 to 2003. The mean Platinum-free interval was 18.2 months with a range of 8 - 48 months. Patients were eligible if they had relapsed more than 6 months after their primary treatments. Patients were evaluated for response after 8 cycles of treatment. CA 125 level was elevated above 175 in all 24 patients. Results: We obtained complete remission in 10 pts (41%). The CR was evidenced by the normalization of CA 125 level and normal imaging studies and physical exm. Partial remission was shown in 7 pts (25%). the remaining 7 pts met the criteria for stable disease. No patient progressed under treatment. Our response rate i.e: CR + PR was therefore 66%. Toxicities included: grade 3 neutropenia in 8% (2/24), grade 1 neurotoxicity in 8%(2/24) and grade 3 anemia in 4%(1/24). The median progression-free survival was 14.8 months with a range of 3 - 27 months. Conclusions: To our knowledge, this is the first study of its kind to date. Our 41% CR rate is impressive in this population of heavily pretreated patients. The results we have achieved in this study are promising and this novel weekly triplet (G.C.D) deserves to be considered in the primary treatment of epithelial ovarian cancer. No significant financial relationships to disclose.
An anti-CEA single chain Fv antibody for radioimmunoguided surgery in colorectal cancer
Authors: A Mayer, GM Boxer, D O'Malley, E Tsiompanou, AA Flynn, BR Davidson, MC Winslet, Aam Lewis, AP Dhillon, Ajw Hilson, Rhj Begent
Journal: Annals of Oncology (1998)
Screening for <i>RET</i> and <i>ROS1</i> fusions in an enriched cohort of pan-negative never-smokers with advanced lung adenocarcinomas to identify patients for treatment in targeted therapy trials.
Authors: Alexander Edward Dela Cruz Drilon, Lu Wang, Adnan Hasanovic, Philippe Joubert, Mark G. Kris, Gregory J. Riely, Marc Ladanyi, Naiyer A. Rizvi
Journal: Journal of Clinical Oncology (2013)

8067 Background: RET and ROS1 fusions have been identified pre-clinically as drivers of tumor growth in lung adenocarcinomas. In addition, based on response to crizotinib in ROS1-positive tumors and emerging data on RET inhibition in some tumors, these fusions represent druggable targets. While each occurs in 1-2% of unselected patients, a screening paradigm based on testing never-smokers whose tumors have no known oncogenic mutations or fusions may enrich identification for ongoing clinical trials. Methods: Patients with a never-smoking history (&lt;100 lifetime cigarettes) and advanced pan-negative lung adenocarcinomas (absence of mutations in EGFR, KRAS, NRAS, BRAF, HER2, PIK3CA, MEK1, and AKT, and ALK fusions) were selected for testing. Screening for RET and ROS1 fusions was performed in real-time via dual-probe FISH breakapart assays, RT-PCR, and next-generation sequencing in selected cases. We enrolled patients onto a phase II trial of cabozantinib for RET fusion-positive lung cancers (NCT01639508) and, as part of the Lung Cancer Mutation Consortium (LCMC), a phase I trial of crizotinib for ROS1-positive lung cancers (NCT00585195). Results: Thirty five (n=35) never-smokers with advanced pan-negative lung adenocarcinomas were identified. A RET or ROS1 fusion was found in 31% [n=10/32, 95% CI, 15-47%] of patients. RET and ROS1 fusions were found in 15% [n=5/34, 95% CI, 3% - 27%] and 15% [n=5/33, 95% CI, 2%-27%] of patients, respectively. 1 patient had a novel TRIM33-RET fusion. 3 of 5 patients with RET fusion-positive tumors were eligible for treatment with cabozantinib, 2 of which had partial responses to therapy. 1 of 5 patients with ROS1 fusion-positive tumors was treated on-protocol with crizotinib and achieved a partial response. Conclusions: 31% of never-smokers with pan-negative advanced lung adenocarcinomas harbor a gene fusion involving either RET or ROS1. Until multiplexed mutation and fusion testing is routinely available, targeting this population for screening represents an interim enrichment strategy for patient identification and enrollment on clinical trials where responses are already being documented.
A phase I/II multicenter study of the chimeric monoclonal antibody NEO102 (NPC-1C) in adults with refractory pancreatic (PC) and colorectal cancer (CC).
Authors: Muhammad Shaalan Beg, Michael Morse, Sandip Pravin Patel, Sharon Mavroukakis, Melony A. Beatson, Philip M. Arlen, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2015)

240 Background: NPC-1C (NEO102) is a novel chimeric monoclonal antibody that recognizes a variant form of MUC5AC expressed specifically by human pancreatic (P) and colorectal (CC) tumors. The mechanism of action is through Antibody-dependent cell-mediated cytotoxicity (ADCC). We are presenting results of dose escalation and preplanned expansion cohort of NEO-102. Methods: This is a Phase Ib/IIa, open label, multicenter clinical trial and expansion cohort of NEO102. Patients are preselected based on an Immunuhistochemistry (IHC) companion diagnostic assay. Antigen expression cut off was set at 20% expression. NEO102 was administered every 2 weeks IV with tumor assessments every 8 weeks. The primary objective was to determine safety and tolerability of NEO102. Secondary objectives include overall survival, clinical benefit, pharmacokinetics and explore the immunologic correlates. Results: Twenty-six patients (3 pancreatic and 23 colon cancer) are evaluable for toxicity and response. Median age is 55 (32 - 68) years, 14 are male. Two dose limiting toxicities were experienced at 4.0 mg/kg: grade 3 hyperbilirubinemia (n=4) and grade 3 anemia (n=1). The maximum tolerated dose (MTD) and recommended phase-2 dose (RP2D) was established at 3.0 mg/kg. Of 12 patients evaluated for response, 5 demonstrated stable disease by RECIST (42%; 4 CC, 1 P) after the first course (Day 57) and 1 PC had SD after the second course (Day 114). OS is 4.5+ months (1+ - 13.5+), median duration of treatment of 74+ days (36-133). Of those screened, 60-70% tumors were IHC positive. Immune correlates (including cytokine profile, HAMA) will be presented. Conclusions: Treatment with NEO102 is well tolerated with a manageable safety profile. RP2D is 3.0 mg/kg. Preliminary results with NEO102 have demonstrated signs of clinical activity based on stabilization of disease in heavily pretreated patients with PC and CC. A Phase II study of NEO102 monotherapy in pancreatic and colon cancer is now enrolling patients. In addition, a combination study using NEO102 with cytotoxic chemotherapy in metastatic pancreatic cancer is underway. Clinical trial information: NCT01040000.
Patterns of PET response after long-term sunitinib therapy in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumors (GIST)
Authors: C. P. Raut, A. Van Den Abbeele, N. Ramaiya, J. A. Morgan, S. George, M. T. Quigley, A. M. Dollard, M. M. Bertagnolli, C. Baum, G. D. Demetri
Journal: Journal of Clinical Oncology (2006)

9547 Background: Sunitinib malate (previously known as SU11248) is an active therapy for GIST patients resistant to or intolerant of IM. During initial development, sunitinib was administered in 4–6 week cycles, with 2–4 weeks of drug dosing followed by 2 weeks off treatment. We previously reported suppression of tumor-related 18FDG avidity on PET imaging during sunitinib dosing, with rebound tumor uptake while off drug. This rebound, seen in 80% with initial PET suppression, did not correlate with lack of clinical benefit. We asked if this pattern persists in pts who benefited from long term (&gt; 2 years) sunitinib therapy. Methods: Of 77 pts in our initial Phase I/II study, 7 remain on therapy with sunitinib for more than 2 years, 4 of whom had matched baseline PET and CT data to assess tumor metabolic activity on and off sunitinib dosing. PET scans were obtained at baseline, during initial treatment, during the off-treatment period, and again after &gt; 2 years therapy. These 4 pts were followed for a median 39 months (range 35–45 months) and for a median of 35 cycles (range 27–47). Two achieved PR and two SD. Results: Initially, all 4 exhibited suppression of tumor FDG avidity with treatment followed by rebound during the off-treatment period. By 6 months, all showed complete suppression of FDG activity. After &gt; 2 years on sunitinib, GIST lesions in 2 pts showed no activity on PET, even while off sunitinib, while GIST in 2 pts demonstrated rebound flare when off therapy. The GIST lesions have not progressed despite the transient metabolic rebound while off sunitinib. Conclusions: Metastatic lesions in pts with IM-resistant GIST benefiting from long-term sunitinib therapy display two patterns on PET imaging. GIST in certain pts who benefit from therapy demonstrates metabolic rebound of activity when off dosing, while lesions in other pts remain metabolically inert on PET even during the brief dosing breaks. Functional imaging may yield insights to differences in the underlying biology of GIST subtypes in different pts. [Table: see text]