tbuckley/cabot-search huggingface dataset:
Patient survival and health care utilization in Medicare beneficiaries diagnosed with cancer of unknown primary
Authors: K. B. Tong, K. N. Murtagh, H. Hubert, B. Santry, A. J. Layton, G. G. Anderson
Journal: Journal of Clinical Oncology (2006)

6064 Background: For patients presenting with cancer of unknown primary (CUP), identifying the site of origin can improve survival and treatment outcomes. We analyzed outcomes in patients who present with an initial diagnosis of malignant neoplasm without specification of site (ICD-9 199.0 and 199.1). Methods: Based on a 5% Medicare beneficiary sample from 2002 through 2004, we conducted a retrospective claims data analysis identifying patients who were cancer free in 2002 and who subsequently had a claim with a CUP diagnosis (ICD-9 199.0 or 199.1) in 2003. We evaluated survival and Medicare charges by procedure and diagnosis code for four consecutive quarters following CUP diagnosis. We assigned patients to one of two groups. The “differential” group consisted of CUP patients having a subsequent claim with a differential diagnosis code (ICD-9 140–229, excluding 199.0 and 199.1). The “unknown” group consisted of CUP patients with no later change in diagnosis. We applied chi-square and t-tests to examine differences in survival, resource utilization, and Medicare charges between groups. We developed Cox survival and linear regression models for multivariate analyses. Results: Of the 388 patients, 277 (71%) did not have a claim with a differential diagnosis during the follow-up period. Both groups were similar in race (80% white) gender (60% female) and age (range 70–79). The one-year mortality of the unknown group was 32.9% compared to 19.8% in the differential group (p=0.01). First quarter charges were higher for the unknown group: $2,549 vs. $1,683 (p &lt; 0.001). Total allowed charges were higher for the differential group over the one-year follow up period: $7,493 vs. $5,540 (p &lt; 0.05), even when adjusted for survival. Conclusions: Following a diagnosis of CUP, patients who obtain a differential diagnosis live longer and incur higher charges over time as a result of ongoing management and intervention. Improved diagnostic tests may affect patient survival and how Medicare resources are applied. No significant financial relationships to disclose.
Effects of low molecular weight heparin on angiogenic factors in advanced cancer patients
Authors: H. Coskun, N. Karakus, H. Vural, O. Akturk, G. Alanoglu
Journal: Journal of Clinical Oncology (2007)

21158 Background: The relationship between cancer and thrombosis is known for many years. Thrombosis can be associated with the biology and therapy of the disease in cancer patients. Low molecular weight heparin (LMWH) is shown to increase the duration of life in several types of cancer in clinical trials. Low molecular weight heparin is thought to be inhibiting with tumor growth and metastasis in several ways. In our study, we evaluate effects of LMWH therapy on angiogenic factors. Methods: Thirty-two advanced cancer patients who used prophylactic LMWH before chemotherapy. Median age was 64.5 years with range from 18 to 80. Sixteen healthy volunteers that are of same age and gender with study patients comprised the control group. VEGF, HGF, FGF, EGF, PDGF, ICAM, p-selectin, e-selectin levels were evaluated before and 7 days after LMWH therapy. Results: In baseline measurements HGF and ICAM levels were higher in treatment group compared the control group. But, levels of EGF and VEGF were not statistically significant higher in the treatment group compared to control group. After LMWH therapy, VEGF, FGF, PDGF, ICAM, e-selectin levels appeared to decrease and HGF, EGF, p-selectin levels appeared to increase but none of these changes were statistically significant. In a subset of seventeen patients with adenocarcinoma, levels of ICAM declined significantly after LMWH therapy this group. Before LMWH therapy; HGF was correlated with PDGF, VEGF, p-selectin, e-selectin; EGF was correlated with p-selectin; e-selectin was correlated with p- selectin. After therapy HGF was correlated with PDGF and EGF; PDGF was correlated with FGF and p-selectin; EGF was correlated with ICAM levels. Conclusions: In summary, with a short course of LMWH therapy a change in anjiogenic biomarkers was observed only in adenocarcinoma patients and this change was limited only to ICAM levels. The study focused on long term course was warranted. No significant financial relationships to disclose.
The Role of the Physician in the Investigation of Aircraft Accidents
Authors: Oliver K. Niess
Journal: JAMA (1963)

Experience of physicians, especially those in the armed forces, has demonstrated the important contribution the medical profession can make to aviation safety. Many complex factors are involved in the investigation of an air disaster and careful planning is important for the physician in overcoming obstacles that may be encountered. Collection and correlation of medical data with other factors relating to an accident are of paramount importance. The disciplines of pathology and toxicology play key roles in accident investigation. Only by gathering detailed data from each accident can the responsible safety agencies document their requirements for the materiel and the operational changes needed to make flying safer.
Radiofrequency ablation as an alternative treatment for renal carcinoma in the elderly
Authors: W. Tan, R. Paz- Fumagalli
Journal: Journal of Clinical Oncology (2004)

4709 Background:Renal Cancer accounts for 31,200 cases of new cancers each year in the US. In the elderly with multiple comorbid conditions the options for treament would include nephrectomy or hospice. Most patients are unfortunately not candidates for surgery and yet most patient would desire treatment. Radiofrequency ablation(RF) effectively uses heat to destroy living tissue. RF works by converting RF waves into heat,results in thermal damage to parenchymal tissue. Methods:We retrospectively reviewed the patients who had RF ablation as treament for their renal cancer, who were 65 years old and above at our institution. All patients had biopsy proven renal cancer. Results: Among the 29 patients who had RF ablation for a renal mass 8 had biopsy proven renal cancer, .Average age was 75. The size of the mass range from 1.6 cm to 4.4 cm. The most common reasons for doing RFA were cardiovascular disease, congestive heart failure, stroke, COPD,other concurrent cancers, history of prior nephrectomy in the other kidney. The most common complications include pain, infection, anemia and bleeding. 4 are still in remission with no recurrence after 12 months follow up and another 2 patients are still in remission for 6 months or more based on CT scan images. Conclusions: RF Ablation can be a safe therapeutic option for renal cancer for elderly patients but the long term effects and duration of remission are not well defined.Our study is limited because of short term follow up.Prospective studies with long term follow up and biopsy after the procedure could hopefully clarify its exact role in the therapy of renal cancers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron Chiron
Predictors of pathologic response to preoperative chemotherapy and concurrent radiotherapy for locally advanced breast cancer
Authors: R. Venkitaraman, S. G. Ramanan, K. R. Rajalekshmy, T. G. Sagar, V. Shanta
Journal: Journal of Clinical Oncology (2009)

e11545 Background: Combined modality treatment is essential for acheiving optimal results in the management of locally advanced breast cancer (LABC). Neoadjuvant chemoradiotherapy is considered a promising approach for LABC. Pathologic complete response to neoadjuvant treatment for LABC predicts prolonged survival. Aim: To determine the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer and to identify the predictors of pCR. Methods: Female patients with noninflammatory LABC received neo-adjuvant chemotherapy with concurrent radiotherapy, and then underwent mastectomy and axillary clearance. The pathologic response was analysed with respect to the baseline clinical factors and the receptor status on immunohistochemical studies of the initial biopsy specimen. Results: Of the 296 patients included in the study, 286 underwent mastectomy. Ninety-two (31 %) patients achieved a pCR. The significant predictor of a pCR was Oestrogen receptor negative status (p = 0.025), while progesterone receptor negative status (p=0.069 ), HER2 status (p= 0.62), age (p= 0.074), stage (p=0.6), grade (p=0.86), type of chemotherapy (p=0.37) and number of cycles of chemotherapy (p = 0.23) did not predict for pathologic response. Clinical complete response predicted for a pathologic complete response (p=0.0001). Conclusions: Neoadjuvant concurrent chemoradiotherapy results in good pathologic complete response rates in LABC. High pathologic compete response rates are achieved in patients with endocrine receptor negative disease, with neoadjuvant chemoradiotherapy, which might result in improved outcome in this high risk subset of patients. No significant financial relationships to disclose.
Abstract 11808: Contemporary Outcomes of Bypass Surgery versus Stent-assisted Endovascular Therapy for Infrainguinal Artery Disease in Patients with Critical Limb Ischemia
Authors: Yoshimitsu Soga, Shinsuke Mii, Osamu Iida, Hitoshi Okazaki, Keisuke Hirano, Kenji Suzuki, Terutoshi Yamaoka
Journal: Circulation (2012)

Background: Little is known about the efficacy of stent-assisted endovascular treatment (EVT) in patients with critical limb ischemia (CLI) compared to bypass surgery (BSX) in a real-world practice. Method: The study was performed as a multicenter retrospective registry. Between January 2004 and December 2009, 1053 CLI patients (1053 first treated limbs) who underwent first BSX (230 patients) or EVT (823 patients) for de novo infrainguinal lesions were identified retrospectively and analyzed. The outcome measures were amputation-free survival (AFS), overall survival, limb salvage rate and freedom from perioperative death (POD) or major adverse limb events (MALE; includes any repeat revascularization and major amputation). Result: The mean follow interval was 35+/-20 months. Elderly patients were more frequent and diabetes, hyperlipidemia, dialysis, current smoker, coronary artery disease and heart failure were greater in the EVT group. Amputation-free survival does not differ between the BSX and EVT group...
Autoantibodies in rheumatoid arthritis: Anti-citrullinated protein antibodies (ACPA) and type II collagen specificities (B cells and autoantibodies: diagnosis and pathophysiology)
Authors: H Mahdi, O Snir, Rikard Holmdahl, P Venables, L Klareskog, M Widhe, Malmström
Journal: Annals of the Rheumatic Diseases (2008)
Use of bone marrow micrometastasis to predict disease-free and overall survival in esophageal cancer: Evaluation of 304 cases
Authors: Y. K. Vashist, K. E. Effenberger, K. Bachmann, K. Pantel, J. R. Izbicki, E. F. Yekebas
Journal: Journal of Clinical Oncology (2009)

4519 Background: The presence of bone marrow micrometastases (BMM) yields prognostic information for patients at higher risk for recurrence and death. Aim of the study was to evaluate the role of BMM in esophageal cancer (EC). Methods: 304 consecutive patients operated for EC and with BMM status were included into the prospective study. BMM were assessed by a pan-anti- cytokeratin monoclonal antibody, A45-B/B3. Associations between BMM status and clinicopathological parameters as well as disease-free (DFS) and overall survival (OS) were calculated with chi-square-, log-rank test and Cox multivariate analysis. Results: Out of 304 patients 109 (35.9%) were BMM positive (BMM+) and 195 (64.1%) negative (BMM-). Significant correlation was found between BMM and tumor size, nodal stage and recurrence (P=0.02, 0.002 and &lt;0.0001). DFS and OS were significantly better in BMM- compared to BMM+ patients (median 44.2 and 31.6 vs. 10.4 and 12.4 months, P&lt;0.0001). Sub-analyses revealed that nodal negative (N-) patients with BMM- had a significant better DFS and OS compared to N- and BMM+ patients (50.8 and 41.5 vs. 18.0 and 16.3 months, P&lt;0.0001). Nodal positive patients (N+) with BMM- had a better DFS and OS compared to N+ and BMM+ patients (22.1 and 24.8 vs. 9.0 and 11.3 months, P&lt;0.0001). In the Cox multivariate analysis BMM was the strongest predictor of DFS and OS with a hazard ratio of 3.1 and 2.9 (P&lt;0.0001). Also tumor size and nodal stage were found to be significant predictors, whereas age and sex were not. All analyses were repeated after stratification of the study group to underlying tumor type (adenocarcinoma (AC) and squamous cell carcinoma (SCC)). Significant differences were found at all levels as reported for the entire study group above within the AC and SCC group as well. Conclusions: To our knowledge this is the largest study evaluating the role of BMM in EC. Survival sub-analyses stratified to nodal and bone marrow status revealed a significant role of BMM in EC. Presence of BMM proved to be the strongest predictor of DFS and OS in AC and SCC of the esophageus. No significant financial relationships to disclose.
Phase I/II trials of thermochemotherapy with S-1/CDDP in patients with advanced gastric cancer
Authors: T. Ogata, J. Nishida, K. Seo, T. Kouno, M. Hamaya, S. Sato, K. Yoshida, A. Tsuchida, T. Aoki
Journal: Journal of Clinical Oncology (2005)

4245 Background: To patients with advanced gastric cancer in whom radical surgery was impossible, FP therapy with 5-FU and CDDP has commonly been administered in Japan. We conducted phase I/II studies of thermochemotherapy, in which 24-hour continuous administration of CDDP and S-1 was combined with hyperthermia, in patients with advanced gastric cancer in whom radical resection was difficult. Methods: The subjects were 11 patients with stage IV. Initially, for the Level 1 regimen, 50 mg/m2 of S-1 was administered for 14 days, and 60 mg/m2 of CDDP was continuously administered for 24 hours on Day 8 of treatment. For the Level 2 regimen, the dose of S-1 was increased to 60 mg/m2, and the dose of CDDP was 60 mg/m2. For the Level 3 regimen, the doses of S-1 and CDDP were established as 70 mg/m2. At all levels, 4 weeks comprised 1 course. Grade 3 toxicity or a more than 2-week delay in the subsequent dosing related to adverse reactions was regarded as DLT. Hyperthermia was performed in the upper abdomen using a Thermotron-RF-8 device for 40 minutes or more on Days 1, 8, 15, and 22 of treatment. Results: A total of 33 courses were performed, with a mean number of 3 courses. At Level 2, the subsequent dosing was delayed for more than 2 week in serial patients; therefore, the Level 2 regimen was regarded as MTD. Grade 3 hematological toxicity was observed in 12% of the patients receiving the Level 2/3 regimens. There was no grade 3 or higher non-hematological toxicity. The response rate was 64% (CR: 0, PR: 7, NC: 4). In the patients who underwent initial treatment, the response rate was 83% (PR: 5, NC: 1); with respect to sites, the response rates for the primary focus, lymph nodes, liver metastasis, and cancerous ascites were 60%, 50%, 100%, and 33%, respectively. Conclusion: Hyperthermia with S-1/CDDP for advanced gastric cancer exhibited potent antitumor effects without serious adverse reactions, suggesting its usefulness. Furthermore, the Level 2 regimen, consisting of 60 mg/m2 of S-1 administered from Day 1 until Day 14, 60 mg/m2 of CDDP administered on Day 8, and hyperthermia performed on Days 1, 8, 15, and 22, which is repeated at 4-week intervals, should be recommended. No significant financial relationships to disclose.
The safety of oral uracil-tegafur plus leucovorin in the treatment of colorectal cancer in patients with partial DPD deficiency.
Authors: D. D. Cubero, A. Del Giglio
Journal: Journal of Clinical Oncology (2010)

e13146 Background: Fluoropyrimidines are the cornerstone of chemotherapeutic regimens for most gastrointestinal tract tumors. The metabolization of these drugs depends on an enzyme called dihydropyrimidine dehydrogenase (DPD). The quantitative or qualitative deficiency of this enzyme is responsible for at least 50% of severe toxicity cases. We evaluated the safety of using oral uracil-tegafur (UFT) in patients with a partial deficiency in DPD. Methods: The study included 5 colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. After a full recovery from all side effects, we changed the regimen to oral uracil-tegafur (300 mg/m2/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle. The DPD deficiency status was confirmed by gene sequencing. Results: We analyzed 22 uracil-tegafur cycles in 5 patients. We did not observe any episodes of grades 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting, and diarrhea). Conclusions: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analyzed. We believe that oral uracil-tegafur plus leucovorin is a safe alternative for the treatment of patients with partial DPD deficiency. No significant financial relationships to disclose.
Durable disease control with sunitinib and everolimus in well-differentiated neuroendocrine tumors of the pancreas with a high ki67 index.
Authors: Karen Paula Geboes, Stéphanie Laurent, Charlotte Verroken, Ercan Cesmeli, Bieke Lambert, Peter Smeets, Aude Vanlander, Frederik Berrevoet, Louis Libbrecht, Liesbeth Ferdinande
Journal: Journal of Clinical Oncology (2014)

e15161 Background: Everolimus and sunitinib have shown clinically meaningful improvements in progression free survival in well differentiated NET of the pancreas. Treatment with these agents is usually suggested in patients with Rindi grade 1 & 2 tumours, with a ki67 index up to 20%. Some patients with well differentiated tumours have a higher ki67 index. Methods: Since 2008, 11 patients with advanced well differentiated NET of the pancreas with a ki67 index of 15% or more (median 23 (IQR: 16–38%)) and uptake of lesions on octreoscan and/or gallium68 dotatoc were treated with sunitinib and/or everolimus. Some also had positive lesions on FDG-PET scan. Results: Four patients showed progression at the time of first evaluation. Two of them had a Rindi grade 2 tumour and two had bone lesions. All were subsequently treated with cisplatinum-etoposide and 3 patients had a response. The median ki67 index in the 7 other patients was 23 (IQR: 18–36%). Overall in these patients, the disease was controlled for a median of 18 (14-23) months on sunitinib and/or everolimus. Three patients have only been treated with sunitinib thus far. Two of them have been referred for PRRT and are alive and well 6 and 16 months after the start of PRRT. Four patients were treated with both sunitinib and everolimus. One of them is alive without treatment after failure of both oral drugs and 21 months after start of PRRT. The 3 remaining patients are still either on everolimus or sunitinib. Conclusions: Sunitinib and/or everolimus may induce a durable disease control in patients with a well differentiated NET of the pancreas with a ki 67 index above 15% and positive lesions on functional imaging with gallium68 dotatoc and/or octreoscan. Uptake on FDG-PET should not refrain from trying these treatments. Patients with bone lesions are less likely to respond.
Abstract PR08: Pulling out all the stops: Exploiting macropinocytosis inhibition for the treatment of pancreatic cancer
Authors: Cosimo Commisso, Craig Ramirez, Rengin Soydaner-Azeloglu, David L. Bajor, Robert H. Vonderheide, Dafna Bar-Sagi
Journal: Cancer Research (2015)

Abstract Oncogenic Ras stimulates macropinocytosis, an endocytic mechanism of fluid-phase uptake that produces large intracellular vesicles known as macropinosomes. Recently, we have linked the macropinocytic uptake of extracellular albumin and its subsequent degradation to amino acid supply and proliferation in Ras-transformed cells. The ability of albumin to serve as a nutrient source in oncogenic Ras-expressing cells is blocked by inhibiting its internalization via treatment with 5-(N-Ethyl-N-isopropyl) amiloride (EIPA). We determined that EIPA treatment diminished the growth of pancreatic tumor xenografts and that this effect was selective for tumors with a high macropinocytic index. Currently, we are exploring the feasibility of employing macropinocytosis inhibition as an anticancer therapeutic modality utilizing an autochthonous mouse model of pancreatic cancer. In these autochthonous tumors, macropinocytosis is a prominent feature of pancreatic cells found in mid- to late-stage PanIN lesions, as well as in fibroblasts and immune cells residing within the tumor stroma. We have found that EIPA treatment results in a rapid and robust reduction in proliferative capacity both in tumor cells and the surrounding stromal cells. Intriguingly, our preliminary data indicates that EIPA treatment reduces the number of activated fibroblasts associated with PanIN lesions, decreases collagen deposition and results in an increase in blood vessel diameter. Studies have demonstrated that targeting components of the extracellular matrix within the tumor stroma can cause expansion of the vasculature, which can be harnessed to improve drug delivery and permeability to the tumor. Altogether, our findings suggest that macropinocytosis inhibition could be exploited not only to target the tumor cells, but also to target the tumor stroma and enhance the delivery of chemotherapeutics. This abstract is also presented as Poster B37. Citation Format: Cosimo Commisso, Craig Ramirez, Rengin Soydaner-Azeloglu, David L. Bajor, Robert H. Vonderheide, Dafna Bar-Sagi. Pulling out all the stops: Exploiting macropinocytosis inhibition for the treatment of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr PR08.
Efficacy of neoadjuvant therapy with cisplatin, fluorouracil, and cetuximab in locally advanced nonresectable epidermoid skin carcinoma
Authors: G. Mamelle, E. Fournier, F. Kolb, F. Janot, P. Duvillard, C. Robert, C. Mateus
Journal: Journal of Clinical Oncology (2009)

e17008 Background: No standard therapy is known for locally advanced unresectable cutaneous epidermoid carcinoma. Chemotherapy (platin ± fluorouracil) and radiotherapy are commonly used separately or in association (1) mostly as palliative treatments. We report six patients with locally advanced unresectable skin epidermoid carcinomas in whom the association of cisplatin, fluorouracil and cetuximab induced a tumor reduction allowing secondary complete surgical resection. Results: All 6 patients had voluminous tumours located on the face (nose, ear, cheek, forhead). For 5 patients, tumours were recurring after one or several surgical resections. One patient had a rapidly progressing non resectable inflammatory tumour on the nose when he was first diagnosed. All patients received 2 to 3 cycles of chemotherapy associating cisplatin 100 mg/m 2 J1, fluorouracil 1,000 mg/m 2 J1–5, cetuximab J1-J8-J15 (J1 = J21). Tolerance was manageable. A dramatic response with rapid tumour regression, allowing subsequent surgical resection was observed for all patients. Histology showed a complete sterilisation without any active tumoral residue in 2 patients and complete resection (R0) in the remaining patients. Conclusions: The association of cisplatin, fluorouracil and cetuximab is approved for treatment of metastatic head and neck carcinoma (2, 3) but has not been evaluated yet in cutaneous epidermoid carcinoma. The dramatic tumor responses observed in our 6 patients warrant evaluation of this association both in the neoadjuvant and in the metastatic settings for patients with non resectable skin squamous cell carcinomas. No significant financial relationships to disclose.