tbuckley/cabot-search huggingface dataset:
Systemic therapy in anorectal melanomas: Does choice of systemic therapy matter?
Authors: Nitin Kumar Singhal, Vikas S. Ostwal, Shailesh V. Shrikhande, Avanish Saklani, Supreeta Arya, Mukta Ramadvar
Journal: Journal of Clinical Oncology (2016)

731 Background: Anorectal melanomas are relatively uncommon and there is no consensus on the optimal systemic therapy regime with survival advantage. Methods: Retrospective analysis of prospectively maintained database of patients treated at our institute between January 2102 and July 2015. SPSS 20 used for statistical analysis. The survival benefit was assessed in the form of progression free survival (PFS) and overall survival (OS) with the systemic therapy. Results: Out of 74 anorectal melanoma patients seen during this period 50 patients had metastatic disease and were evaluated for outcome analysis. Median follow up of patients was 8 months. Of these 50 patients, 36 received chemotherapeutic regimes (taxanes with platinums with or without oral metronomic therapy (OMT), dacarbazine/temozolamide or OMT alone) as per the description of treating physician, while 11 patients did not receive any systemic therapy due to poor general condition at presentation, or refused therapy. 3 patients defaulted during the initial work up. Median age at presentation was 54 years and common sites of metastasis were Liver, lung and lymph nodes. Median OS for patients who underwent excision was 22 months. In patients who received systemic therapy median OS was 13 months versus 8 months for those who did not receive it (p = 0.253). The Median PFS after 1st line systemic therapy was 3 months. 5 patients had grade III toxicities in the form of neutropenia, diarrhea. PFS was 3 months for temozolamide/dacarbazine, OMT along with chemotherapy or OMT alone whereas it was 5 months for taxanes with platinum. (p = 0.045). OS was 11 months for OMT with or without chemotherapy and 18 months for taxanes with platinum (p = 0.43). Conclusions: Palliative systemic therapy has some survival advantage in metastatic anorectal Melanomas. Taxanes with platinums appear to be the most efficacious among the presently used regimens even in anorectal melanomas. OMT also has the survival benefit with the advantage of oral therapy in palliative setting
The effect of early palliative care consultation for survival in patients with unresectable pancreatic cancer.
Authors: Kazuhiro Kosugi, Fumio Omata, Yoshiyuki Fujita, Akitoshi Hayashi
Journal: Journal of Clinical Oncology (2016)

131 Background: Additional early palliative care consultation (EPCC) on standard oncology care (SOC) was reported to prolong survival of patients with metastatic non–small cell lung cancer by one randomized controlled trial. However, its survival benefits for the patients with other advanced cancer have not fully been investigated yet. Pancreatic cancer is one of neoplastic diseases which seldom can be diagnosed in early stage and it is important to know the effectiveness of EPCC. The aim of this study was to determine the effectiveness of EPCC for survival of unresectable pancreatic cancer(UPC). Methods: A retrospective cohort study was conducted in tertiary referral hospital in Tokyo, Japan. 98 patients were diagnosed with UPC between Jan 2004 and February 2007. Candidate variable as predictors for survival analysis included basic characteristics of patients such as age and gender, EPCC, American Joint Committee on Cancer (AJCC) stage, Charlson comorbidity index (CCI), ECOG performance status (PS), and chemotherapy. EPCC was defined as referral to board certified palliative care physician within 30 days after initial diagnosis of UPC. Patients were classified to EPCC with SOC and SOC only group. Bivariate analyses was conducted to compare EPCC with SOC and SOC group. Kaplan-Meier estimates were calculated. Cox proportional hazard model was applied for multivariate analysis. Results: The basic characteristics of patients are described in table. Median estimates of survival [95%CI] were 64 days[21-99] in the group of EPCC with SOC, and 132 days [69-174] in the group of SOC only (P=0.0065, Log-rank test). Adjusted hazard ratio [95% CI] of AJCC stage, chemotherapy, and EPCC was 1.82 [1.02-3.49], 0.41 [0.25-0.70], 2.02 [1.03-3.70], respectively. Conclusions: EPCC may be a significantly poor prognostic factor in the patients with UPC. [Table: see text]
Sleep In Patients with Sickle Cell Anemia and Priapism. A Case-Control Study
Authors: Marina Roizenblatt, Frederico Pollack-Filho, Joao R Sato, Perla Vicari, Francisca Veloso, Martha Mariana A S Arruda, Sergio Tufik, Suely Roizenblatt, Maria Stella Figueiredo
Journal: Blood (2010)
A phase II open trial evaluating imatinib mesylate and zoledronic acid in patients with chronic myeloid leukemia with molecular residual disease
Authors: G. Etienne, S. Mathoulin-Pélissier, M. Fort, A. Guerci-Bresler, F. Guilhot, P. H. Rousselot, F. E. Nicolini, L. Legros, C. Cholet, J. Reiffers, F. Mahon
Journal: Journal of Clinical Oncology (2008)

18006 Background: The aim of this study was to evaluate whether or not a CMR could be induced by addition of zoledronic acid in patients with CCR during IM therapy. Indeed, this ras signaling inhibitor has shown significant anti leukemic activity in vitro against imatinib resistant cells and in vivo in mouse models of CML. Methods: A single arm multicenter phase II study was designed. This two stages design requires an overall sample size of 37 patients to assess the ability of the association of zoledronic acid and imatinib to achieve a complete molecular response and/or a BCR-ABL transcript rate reduction >2 log after a six-months treatment. Only chronic phases of CML treated for at least one year by imatinib, with a daily dose of 600 mg or more during at least four months and maintaining a complete cytogenetic response for at least one year, with a detectable BCR-ABL transcript by RT-PCR were included. The schedule regimen was as follows: 600 mg/day of imatinib in addition to 4 mg every three weeks of zoledronic acid (intravenous injection) during six months. The BCR-ABL transcript rate was assessed every six weeks by quantitative RT-PCR. Results: During the first stage, 17 pts were included. Among these pts, 12 had the complete treatment and 5 were withdrawn before: four for intolerance and one for progression with a BCR-ABL transcript rate increased to 1 log (week 21). The intolerance phenomenons consisted in: grade 2 persistent renal failures (week 6), grade 3 arthralgia (week 9), grade 2 bone pain and gingival recession with bleeding (week 18). After the first stage, none of the seventeen patients presented with a CMR or a Bcr-Abl transcript rate reduction > 2 log after six months of the association IM plus zoledronic acid. The median ratio of BCR-ABL/ABL transcripts was maintained stable on 6 months of treatment. Therefore, we concluded to no improvement of the zoledronic acid to imatinib treatment. Conclusions: The results tend to confirm those reported by Pavlu J et al. for the patients in complete hematological response (BJH 2007;137:423–428). However, taking into account of the possible immunological effect of zoledronic acid, a longer follow up will be necessary to draw a definitive conclusion. This work was supported by a grant from Novartis France No significant financial relationships to disclose.
Impact of diabetes mellitus on risk of major vessel invasion and distant metastasis in hepatocellular carcinoma.
Authors: G. C. Connolly, S. Safadjou, R. Kashyap, R. Chen, A. Ndauguba, R. Dunne, B. Maliakal, A. A. Khorana, M. Orloff, A. F. Hezel
Journal: Journal of Clinical Oncology (2011)

174 Background: Diabetes mellitus (DM) is identified as a negative prognostic indicator in hepatocellular carcinoma (HCC), though the basis for this is unknown. Methods: We conducted a retrospective review of 279 advanced and 191 transplanted HCC patients diagnosed between 1998 and 2008. Logistic regression analyses were conducted to assess the effect of clinical DM on clinical outcomes including distant metastasis and vascular invasion. Results: Eighty- four of 191 (44%) transplanted patients had DM at time of transplantation and 97 of 279 (34%) nontransplanted patients had DM at the time of diagnosis. The presence of DM was associated with an older age at time of diagnosis and a higher prevalence of hepatitis C virus (HCV) and nonalcoholic steatohepatitis (NASH). Also 30% (30/97) of diabetics compared to only 9.3% (17/182) of nondiabetics (p&lt;0.0001) among the cohort with advanced disease had distant metastasis at the time of initial diagnosis, and this difference remained significant when adjusting for CLIP stage, age, and etiologic risk factors in a multivariate logistic regression analysis (OR=8.3, p&lt;0.0001). The association of DM with invasive disease was echoed among early stage transplanted HCC patients in whom histologically confirmed macrovascular invasion was higher among patients with DM compared to those without (20.5% vs. 9.5%, p=0.032). The association of DM with increased risk of macrovascular invasion remained significant in a multivariate logistic regression analysis when adjusting for tumor size, number of nodules, age, obesity and etiologic risk factors (OR=3.2, p=0.025). Conclusions: DM was associated with significantly higher incidence of histological macrovascular invasion in a large cohort of HCC patients receiving liver transplantation and a significantly higher rate of distant metastatic disease at diagnosis in a large cohort of HCC patients with advanced disease. No significant financial relationships to disclose.
A phase I and pharmacokinetic (PK) study of high dose selenomethionine (SLM) in combination with irinotecan (IRI) in patients with advanced solid tumors
Authors: Y. Rustum, L. Pendyala, P. J. Creaven, P. Smith, R. Azrak, S. Cao, F. Durrani, D. D. Lawrence, V. Badmaev, N. C. Diane, M. G. Fakih
Journal: Journal of Clinical Oncology (2005)

2080 Background: SLM, an organic selenium (Se) compound, potentiates IRI activity, protects against toxicity, and allows dose-escalation of IRI in pre-clinical models. IRI dose-escalation in mice models was possible only in association with serum Se concentrations > 1200ng/ml. We initiated a phase I study of daily SLM with weekly IRI to investigate: 1) the maximum tolerated dose (MTD) of IRI when combined with high dose SLM; 2) the pharmacokinetics (PK) of both compounds. Methods: IRI was escalated in a standard 3+3 design. SLM was administered at a fixed dose of 2200 μg/day starting 1 week before the 1st dose of IRI. IRI was administered intravenously weekly x 4 repeated every 6 weeks (1cycle). Dose level (DL) 1 and DL2 consisted of IRI 125mg/m2 and 160mg/m2 respectively. Blood for Se was drawn on days 1, 2, 8, 15, 29 and 50 (and later where possible). Results: 10 evaluable pts were treated on study (M/F: 6/4; median age: 59; ECOG 0/1: 3/7; prior chemo: 10). At DL2, 3 out of 4 pts had G3 diarrhea (DLT). None of the 6 DL1 pts had a DLT (declared MTD). Diarrhea was ≤ G2 (1 pt with G2) and neutropenia ≤ G2 at DL1 except for 1 pt with G4 neutropenia. SLM was associated with mild intermittent garlic-like breath. Se PK showed a suboptimal concentration <1000 ng/ml on day 1 of IRI. The mean Se (SD) serum half-life was 183 (94) h, and CLt/F 0.10 (0.04) L/h. Modeling of data suggests steady state attainment after ∼30 days, with a median Se steady state level of 844 (range 585 -1300) ng/ml. Responses were evaluable in 8 patients: 1 pt with prior IRI-refractory colon cancer had a partial response that is ongoing (11 months +). This patient had complete reversal of total alopecia upon built up of Se concentrations > 1200 ng/ml. 4pts had prolonged stable disease (Colon, NSCL, pancreatic, and gastric cancer). Conclusions: The administration of SLM at 2200 μg PO QD is safe but does not allow IRI escalation > 125mg/m2/week. Unexpected responses and disease stabilizations were noted at the MTD suggesting possible synergy between SLM and IRI. The inability to escalate IRI may be related to suboptimal concentrations of Se on D1 of IRI. SLM escalation in combination with fixed dose IRI is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sabinsa Sabinsa
Population-based trends in positron emission tomography (PET) utilization after resection for colon cancer.
Authors: Christina Edwards Bailey, Chung-Yuan Hu, Y. Nancy You, Miguel A. Rodriguez-Bigas, Harmeet Kaur, Randy Ernst, John Michael Skibber, George J. Chang
Journal: Journal of Clinical Oncology (2013)

365 Background: While most colon cancer staging and treatment guidelines do not routinely include PET imaging, its use has been increasing. The primary aim of this study is to evaluate the trends in PET utilization during the first 2 years after diagnosis of colon cancer. Methods: A retrospective cohort study of patients ≥ 65 years old with colon cancer who underwent surgical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (2001-2007, Medicare Part A/B only) and had at least 2 years of follow-up was performed. PET utilization was assessed using the test for trends and multivariate logistic regression for patient, tumor and treatment response characteristics. Results: Of 28,762 patients who underwent primary resection of colon cancer, 3,897 (13.6%) had at least one PET scan within 2 years after surgery. The utilization rate steadily increased from 7.5% in 2001 to 18.7% in 2007 (p = 0.01). A total of 7,175 PET scans were performed on 3,897 patients, among which 2,348 (60.2%) had 1 PET scan, 834 (21.4%) had 2 PET scans and 715 (18.4%) had &gt;2 PET scans. The majority of PET scans were performed within 2 months after surgery (n=1314) and a 2 nd peak was observed at 9 months. Additional factors significantly associated with increased PET scan use included SEER region, stage, and grade (Table). Conclusions: The utilization of PET scans after colon cancer resection has steadily increased since 2001 with the majority of PET scans being performed within 2 months after surgery and its use was subject to geographic variation. Further study is needed to examine the impact of this pattern on long-term oncologic outcomes. [Table: see text]
Phase II trial of sequential dose-dense epirubicin/cyclophosphamide (E/C) followed by docetaxel/capecitabine (D/X) as adjuvant or neoadjuvant chemotherapy for patients with HER2-negative breast cancer (BC)
Authors: S. De la Cruz, J. M. Aramendia, J. Espinós, O. Fernandez-Hidalgo, M. Santisteban, L. Arbea, J. Aristu, C. Garran, R. Martinez-Monge, F. Martinez-Regueira, Y. Nieto
Journal: Journal of Clinical Oncology (2008)

635 Background: Recent improvements in adjuvant chemotherapy for HER2- BC include: 1) dose density and 2) concurrent or sequential anthracycline/taxane regimens. Further, the addition of capecitabine to docetaxel (D/X) may prove valuable in this setting, based on its superiority over docetaxel alone in metastatic breast cancer (MBC), which is possibly explained by docetaxel-induced upregulation of thymidine phosphorylase (TP), the target of capecitabine. In addition, immediate prior use of E/C also upregulates tumor TP. We report the results of dose-dense E/C followed by D/X in patients with HER2-negative nonmetastatic BC. Methods: Pts with HER2-, either node-positive (N+) or locally advanced breast cancer (LABC), and normal end-organ function were eligible. Treatment included 4 cycles of dose-dense E/C (100/600 mg/m2) + G-CSF Q2 weeks, followed by 4 cycles of docetaxel (75 mg/m2)/capecitabine (1,000 mg/m2 Q12 hours x 14 days) Q3 weeks. LABC pts were treated preoperatively. Subsequently, all pts received radiotherapy, and hormone treatment if estrogen (ER) or progesterone receptor (PR) +. Results: 55 pts were enrolled: 35 N+ (median 2 nodes involved, range 1–13), 20 LABC. Median age was 50 (27–73). ER and PR were present in 80% and 72% of tumors, respectively. Five pts developed grade (G) 3 neutropenic fever (4 after E/C, 1 after D/X). Hand-foot syndrome (HFS) was prominent (45% G3) in the first 20 pts (1,000 mg/m2 of capecitabine). The dose of capecitabine was subsequently reduced to 800 mg/m2. At this dose, the next 35 pts had only 14% G3 HFS. No G4–5 toxicities were observed. All 20 patients treated preoperatively responded clinically, with 10 CRs. Six patients (30%) experienced a pathological CR, and 3 additional patients had pT0N1 tumors. At median follow-up of 2 (1–2) years only 2 pts have relapsed, with event-free and overall survival rates of 96% and 98%, respectively. Conclusions: Sequential dose-dense E/C followed by D/X (requiring a lower capecitabine dose than that approved for MBC) has favorable toxicity and activity profiles for the adjuvant or neoadjuvant treatment of HER2- BC. These early encouraging results warrant further testing of this combination. No significant financial relationships to disclose.
Microsatellite high colorectal cancer: Does the underlying mechanism for instability matter?
Authors: John Robert Hyngstrom, Miguel A. Rodriguez-Bigas, George J. Chang, Melissa W. Taggart, John Michael Skibber, Barry W. Feig, Y. Nancy You
Journal: Journal of Clinical Oncology (2012)

575 Background: Microsatellite instability (MSI) testing in colorectal cancer (CRC) provides prognosis, predicts chemotherapy response, and guides diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. MSI can be sporadic or hereditary, arising from somatic or germline mutations in DNA mismatch repair (MMR) genes respectively. The clinical implications of these distinct mechanisms are uncertain. Methods: Patients who underwent MSI testing for CRC between 2000 and 2011 were identified. MSI-high (MSH) CRCs were defined by: pathogenic mutation in MMR genes; &gt;30% of markers with allelic shift in PCR-based MSI testing; or loss of expression in at least 1 MMR protein on immunohistochemistry. The subset with MLH1 gene promoter methylation, BRAF mutation, or EPCAM mutation was considered sporadic. Clinicopathologic features and disease-free survival (DFS) were examined in reference to microsatellite stable (MSS) CRCs. Results: MSH CRC’s, 92 germline and 49 sporadic, were compared with 105 MSS CRCs. Compared to MSS CRCs, both germline and sporadic MSH CRCs more commonly arose in the proximal colon (63% and 92%, vs. 30%; p&lt;.001), exhibited mucinous/signet ring histology (40% and 47%, vs. 16%; p&lt;.001) and lymphocytic infiltrate/Crohn’s like reaction (15% and 49%, vs. 8%; p&lt;.001). Further comparison between germline vs. sporadic MSH CRCs revealed significant differences in median age (44 yrs. vs. 66; p&lt;.001), proximal colon tumor location (63% vs. 91%; p&lt;.001), AJCC stage (33% vs. 51% Stage III or IV; p&lt;.025) and presence of lymphocytic/Crohn’s like reaction (49% vs. 15%, p&lt;.001). Moreover, sporadic MSH CRCs more often had poor prognostic features including poor differentiation (51% vs. 28% in germline, p&lt;.025) and lymphovascular invasion (57% vs. 34% in germline, p&lt;.007). No difference was observed in stage-stratified DFS between germline vs sporadic MSH CRCs. Conclusions: Patients with sporadic MSH CRCs exhibit distinct clinicopathologic features compared to those with germline MSH tumors. Despite poor prognostic features, no apparent survival difference was observed. Further characterization of these distinct groups is warranted to explain the discordance between risk factors and outcomes.
Targeted siRNA inhibition of NPM-ALK in anaplastic large cell lymphoma causes disease specific growth inhibition which augments chemotherapeutic agents
Authors: F. Y. Hsu, W. F. Anderson, P. B. Johnston
Journal: Journal of Clinical Oncology (2005)

9517 Background: The chromosome translocation t(2;5)(p23;q25) results in the formation of a fusion gene of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which is found in about 50% of anaplastic large-cell lymphomas (ALCLs). The fusion protein contains a constitutively activated ALK kinase that transforms cells through stimulating several mitogenic signaling pathways, such as phospholypase C-; STAT3- and STAT5; PI-3 kinase, and the recently identified Src kinase-mediated pathways. All these signaling events promote cell proliferation or anti-apoptosis effects. These data suggest that NPM-ALK plays an important role in regulating cancer cell growth and that inhibiting the action this fusion protein could be an effective cancer therapy. Methods: We developed an RNA interference system to efficiently and specifically down-regulate the expression of the fusion protein in lymphoma cell lines by designing NPM-ALK-targeting siRNA complementary to the breakpoint; therefore, an oncogene-specific gene targeting is accomplished in ALCL cells. Cell viability, proliferation, and apoptosis was measured after NPM–ALK repression. Results: We observed a cancer type-specific viability loss only in t(2;5)-positive ALCL cell lines, SUDHL 1 and Karpas 299, but not in lymphoma cells lacking the chromosome translocation, Jurkat and Granta 519. Dual mechanisms were identified in causing viability loss, including down-regulated cell proliferation and modestly increased cell apoptosis. Chemotherapy drug, doxorubicin, induced cell apoptosis increased synergistically with NPM-ALK repression, suggesting NPM-ALK repression sensitizes the ALCL cells to chemotherapy. A prolonged effect on cell growth was observed in the ALCL cells, noting lower colony formation ability associated with the siRNA-mediated temporary gene targeting. Conclusions: These results reveal the importance of continuous NPM-ALK expression in maintaining lymphoma cell growth, and suggest a novel combinational therapy specifically for NPM-ALK-positive ALCLs aimed at repressing the fusion gene with chemotherapy treatment. No significant financial relationships to disclose.