tbuckley/cabot-search huggingface dataset:
A simple technique for cranio-spinal irradiation in young pediatric patients
Authors: R. V. Prabhakar, P. Julka
Journal: Journal of Clinical Oncology (2007)

12501 Background: Craniospinal irradiation (CSI) is a complex radiotherapy technique. The implementation of craniospinal radiation makes atleast one junction between orthogonal cranial and spinal radiation fields. The traditional problem with CSI has been the concern over the dose delivered to the junctional area. We are presenting a simple technique of CSI which is easy to plan, treat and delivers a uniform dose to the entire cord. Methods: Ten patients of medulloblastoma suitable for CSI were taken in this study. All patients underwent CT based treatment planning. The patients were immobilized in prone position using the combination of uniframe and vacloc. CT scanning was performed for all the patients with 5 mm slice thickness. The cranium was treated with a dose of 36 Gy in 20# over 4 weeks and the spine with a dose of 30Gy in 20# over 4 weeks. Subsequently, the cranium was boosted to a dose of 20 Gy in 10 fractions over 2 weeks. For the cranial region, parallel opposed fields were used with half beam block provided by asymmetric jaws with the central axis in the caudal edge of the field. Subsequently, the gantry was brought to head top position and the couch was brought vertically down. The field length was opened to desired position to treat the spine by asymmetric jaws. In treatment planning system, doses were prescribed to the reference point placed in the cranial and spinal field. The maximum, minimum and mean dose to each anatomical structure was computed from dose volume histogram by summing the cranial and the spinal treatment plans. The junctional dose was calculated with special emphasis on field junction. Results: The results showed that the junction between the cranial and the spinal fields received relatively uniform dose. The hot spots in the cranial field were reduced by applying field in field technique. The daily setup time required for the treatment was considerably reduced with this technique. Patient with spinal field less than 30 cm from C2-C3 junction to the S1-S2 junction are ideally suited for this technique. Conclusions: Our technique of craniospinal irradiation is simple and technically sound. This technique can be applied for young pediatric patients undergoing CSI. The technique effectively deals with craniospinal irradiation No significant financial relationships to disclose.
Colorectal cancer survival following adjuvant chemotherapy with weekly i.v. fluorouracil 425 mg/m<sup>2</sup> and folinic acid 50mg
Authors: M. B. Jameson, M. Head, S. Deva
Journal: Journal of Clinical Oncology (2009)

e15089 Background: Adjuvant chemotherapy for colorectal cancer (CRC) using fluorouracil (5FU) and folinic acid (FA) has been proven effective and the QUASAR trial showed that a weekly administration schedule was as effective as, and less toxic than, the same daily doses delivered over 5 days every 4 weeks (the “Mayo regimen”). However the 5FU dose used (370 mg/m 2 ) was lower than in some trials and a higher 5FU dose was considered desirable if tolerated. We therefore implemented a weekly regimen using 5FU 425 mg/m 2 and DL-folinic acid 50mg in 2001 and retrospectively evaluated its efficacy and tolerability. Methods: Patients with non-metastatic CRC at assessment by medical oncologists in this institution between 2001 and 2004 were included in the analysis. Data was gathered on patient characteristics, duration of adjuvant chemotherapy and survival. Actuarial survival was calculated using the Kaplan-Meier method. Results: 417 patients (pts) were seen: 181 females, 236 males; median age 67 yrs (24–89); 291 with colon cancer, 126 with rectal cancer; 1 stage 1; 100 stage 2, 316 stage 3. Median follow-up was 6.2 years. 210 pts with colon cancer received adjuvant weekly 5FU/FA (32 stage 2, 178 stage 3) as did 58 pts with rectal cancer (50 of whom also received concurrent chemoradiation). 75% of pts with colon cancer received all 30 planned doses and 59% of rectal cancer pts received all 20 planned doses. 3 year survival for all pts treated with this regimen was 83.0% and for the subgroups with colon and rectal cancer it was 82.4% and 84.5% respectively. For stage 2 and 3 colon cancer pts treated with this regimen 3 year survival was 87.9% and 76.0% respectively; for stage III rectal cancer pts it was 84.1%. Conclusions: These outcomes compare favorably on indirect comparison with results from the QUASAR trial (which reported 3 year survival of 70.6%) and suggest that using a higher 5FU dose in this regimen is tolerable and may be advantageous. No significant financial relationships to disclose.
A humanizedaAnti-CD40 monoclonal antibody (SGN-40) demonstrates antitumor activity in non-Hodgkin’s lymphoma: Initiation of a phase I clinical trial
Authors: J. G. Drachman, C.-L. Law, R. R. Furman, K. Baumgartner, L. A. Kunkel, K. Ryan, D. Miller, M. McDonald, I. S. Grewal
Journal: Journal of Clinical Oncology (2005)

6572 Background: CD40, a member of the Tumor Necrosis Factor (TNF) receptor family, is expressed on the cell surface of normal B lymphocytes, their progenitors, and B cell malignancies, including both indolent and aggressive forms of non-Hodgkin’s lymphoma (NHL). Because this represents an attractive target for immunotherapy, a humanized monoclonal anti-CD40 antibody (SGN-40) has been developed and tested in preclinical models. Methods: SGN-40-dependent proliferation and cell killing were tested in vitro using normal B cells and malignant lymphoma cell lines. Antibody-dependent cell-mediated cytotoxicity (ADCC) was assessed by adding peripheral blood mononuclear cells or purified NK cells to malignant cell lines in the presence of SGN-40. In vivo activity of SGN-40 was determined by xenograft models in SCID mice. Results: Although SGN-40 induces proliferation of normal B cells when crosslinked and exposed to exogenous IL-4, there was dose-dependent B cell depletion and no evidence of activation in non-human primates. Furthermore, malignant cell lines undergo significant antibody-induced cell death (AICD) via apoptosis and ADCC in vitro. SGN-40 is highly active in xenotransplant models, in which Ramos and IM9 cell lines are injected into SCID mice. Mice receiving control IgG died by day 35 whereas those receiving SGN-40 4 mg/kg x 5 doses survived until day 90. Furthermore, these effects are seen in the SCID-beige mice, which lack significant NK cell activity (i.e. ADCC). SGN-40 has in vivo activity in transplanted malignant cell lines that are markedly resistant to rituximab and shows synergy when used together with anti-CD20 therapy. Conclusions: Based on these encouraging data, as well as adequate safety data from non-human primates and an ongoing trial in multiple myeloma, we have initiated a phase I dose escalation trial of SGN-40 in NHL. Anti-CD40 mAb will be given for four consecutive weeks at 2–16 mg/kg/week. Pharmacokinetic data, development of human anti-human antibodies, toxicity, and clinical responses will be evaluated carefully in this heavily pre-treated population of patients. This study is currently open in four sites and patient accrual has begun. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Seattle Genetics Seattle Genetics Seattle Genetics
Surgery for limited-stage small cell lung cancer, should the paradigm shift? A SEER-based analysis
Authors: D. Schreiber, J. Rineer, D. Vongtama, A. Kim, A. Wortham, P. Han, K. Choi, M. Rotman
Journal: Journal of Clinical Oncology (2008)

7525 Background: Although chemotherapy with radiation is currently recommended in limited-stage small cell lung cancer (L- SCLC), several small series have reported improved survival outcomes in those who underwent surgical resection. We employed a US population based database to determine if there is a survival benefit to surgery in the management of L-SCLC. Methods: The Surveillance, Epidemiology and End Results (SEER) registry was used to identify patients with L-SCLC between 1988–2003 coded by SEER as limited or regional disease. Kaplan-Meier analysis was used to compare overall survival (OS) for all patients. Stratifications included stage, type of surgery and whether or not they received radiation. Chemotherapy data is not available in the SEER database. Results: 15,384 patients were identified, of whom 1,469 had surgery (9.5%). 380 of these patients also received radiation therapy (S + RT). Of those who had surgery, 940 underwent lobectomy, 404 underwent wedge resection and 125 underwent pneumonectomy. Surgical resection was associated with improved median survival in both those with limited (63 vs 15 months, p=<0.001) and regional disease (24 vs 12 months, p=<0.001) compared to those who did not have any surgical procedure. In the 940 patients who were able to undergo lobectomy, median survival was 53 months (95% CI 45.4–60.6). Of those who didn't have surgery but did have radiation, median survival was 19 months (95% CI 17.9–20.1) for limited disease and 15 months (95% CI 14.6–15.3) for regional disease. However, the addition of radiation to surgery (S + RT) did not provide any additional survival benefit. Conclusions: In this large series of surgery for L-SCLC, the addition of surgical resection, particularly lobectomy, results in dramatic improvements in OS. The role of surgery in the curative management of L-SCLC should be evaluated in a prospective setting. No significant financial relationships to disclose.
Abstract 16308: Shear Stress triggers an Integrin-Dependent Recruitment of Potassium Channels to the Plasma Membrane of Atrial Myocytes
Authors: Hannah Boycott, Raphael Martins, Camille Barbier, Gilles Dilanian, Alain Coulombe, Stephane Hatem, Elise Balse
Journal: Circulation (2012)

During the cardiac cycle atrial myocytes are continuously exposed to shear stress (SSt), which occurs when laminar sheets of cells move relative to each other. Physiological levels of SSt can modul...
A phase II study of pegylated liposomial doxorubicin (PLD) and gemcitabine (G) in the treatment of hepatocellular carcinoma (HCC) not suitable for loco-regional therapy
Authors: D. Pastorelli, G. Cartei, F. Zustovich, S. Zovato, G. Artioli, R. Ceravolo, M. Nicoletto, S. Binato, M. Mattiazzi
Journal: Journal of Clinical Oncology (2007)

4585 Background: There is no gold standard pharmacological treatment for HCC not suitable for loco-regional therapy. Antracyclines have been often used for the chemotherapy of HCC with low efficacy and well known toxicity. Availability of new drugs and in particular of PLD could enhance the chance of treatment and contain side-effects. Gemcitabine is active against the most solid tumors. Patients and Methods: We enrolled 35 patients (PTS) with histological diagnosis of HCC not suitable for loco-regional treatment and adequate haematological function.; median age was 63.2 (range 44.0–77.4); male/female=29/6; PS=0 in 30 PTS, PS=1 in 4 PTS and PS=2 in 1 PT. Eighteen PTS had metastatic disease. Prior treatments were TACE in13 PTS, PEI in 9, surgery in 12, RFTA in 5 and chemotherapy in 3. Nineteen patients had Child-Pough A-B cirrhosis HBV-HCV related. PLD was administered at the dose of 30mg/m 2 over a 60’ infusion every 28 days and G at the dose of 1,000mg/m 2 over 30’ infusion days 1 and 8 every 28 days. Instrumental response evaluation was performed every 3 cycles and treatment was continued until disease progression or major toxicity evidence. Results: All PTS were valuable for toxicity: G1–2 toxicity was neutropenia in 5 PTS, thrombocytopenia in 7, mucositis in 3 and PPE in 3. G3–4 toxicity was neutropenia in 6 PTS and thrombocytopenia in 1. Thirty-four PTS were valuable for response with CR in 2, PR in 6, SD in 12 and PD in 14. Thirty-four PTS were valuable for TTP: median was 6.2+ months (range 1.9–31.7+). All PTS were valuable for OS: median was 8.8+ months (range 1.9–36.5+). Conclusions: The combination of PLD and G is safe and effective in treatment of HCC. No life-threatening toxicity was experienced and disease control rate was about 60%. No significant financial relationships to disclose.
Abstract 11795: Smooth Muscle Cells From the Arterial Anastomosis Are the Major Precursors of Forming Neointima in Both Artery and Vein Grafts
Authors: Jizhong Cheng, Ming Liang
Journal: Circulation (2014)

Introduction:  Smooth muscle cell (SMC) accumulation leads to neointima formation in injured vessels. Multiple sources for neointima SMCs have been found.   Hypothesis:  The local SMCs or their precursors from anastomosed arteries are the major contributors to neointima formation in artery or vein grafts.   Methods:  To identify the sources of the neointima cells, we use the Wnt1-Cre mice to label and track SMCs in the neighboring arteries and to study their contribution to neointima formation.   Results:  SMCs in common carotid artery were labeled with LacZ or GFP in LacZ-Stop flox /Wnt1-Cre and in RFP flox -GFP/Wnt1-Cre mice, respectively. Two graft models, vein or artery grafts, were studied. The common carotid arteries in these transgenic mice were anastomosed with donor arteries or veins from wild type mice. In artery grafts, the labeled cells in the neointima were evaluated after 1 month, > 90% of neointima cells were originated from the anastomosing host arteries. Most of the neointima cells were also smooth muscle α-actin (SMA-α) positive and expressed smooth muscle myosin heavy chain (SMMHC), the SMC terminal differentiated marker. In vein grafts, about 60% SMA-α + -cells were from anastomosing arteries. Bone marrow cells did not contribute to neointima SMCs in vein grafts, but do costained with markers of inflammatory cells. Wnt1 expression was not detected in the neointima cells in vein grafts, artery grafts, and in injured femoral arteries. Neointima SMCs showed synthetic phenotype and were positively labeled with BrdU  in vitro  and  in vivo . Treatment with IGF-1 receptor inhibitor suppressed SMC proliferation and neointima formation in vein grafts.   Conclusions:  Our results indicate that the SMCs from neighboring artery predominate the neointima cells in vein and artery grafts. Wnt1-Cre mice could be used to explore the role of SMC from neighboring vessel in vascular remodeling.
Impact of preoperative radiation dose escalation on pathologic outcomes and radiation toxicity in locally advanced rectal cancer (LARC): A matched-pair analysis.
Authors: C. B. Patel, K. M. Kattepogu, I. J. Park, C. Eng, M. E. Delclos, B. W. Feig, C. H. Crane, J. M. Skibber, P. Das, M. A. Rodriguez-Bigas, S. Krishnan, G. J. Chang
Journal: Journal of Clinical Oncology (2011)

e14036 Background: Compared with postoperative chemoradiotherapy (CRT), preoperative CRT has been shown to improve local control and reduce toxicity for LARC patients. However, the dose of preoperative RT in such regimens is empirically chosen based on experience with postoperative CRT regimens. We hypothesized that higher RT dose improves tumor downstaging without increasing toxicity. Methods: Between 1995 and 2003, LARC patients were treated with preoperative RT and concurrent protracted venous infusion 5-fluorouracil (5FU). 76 patients in the high dose (boost) CRT group (5FU + 52.5 Gy in five weeks, 1.8 Gy/morning and an additional 1.5 Gy/afternoon in the fifth week) were matched (based on type of surgery and clinical T/N stage) with 76 patients in the low dose CRT group (5FU + 45 Gy in five weeks, 1.8 Gy/day). Radiation toxicity, pathological complete response (pCR), and T downstaging were tabulated. Discrete and categorical variables were compared using McNemar’s chi-square test. Results: Both groups were balanced for patient gender, age, and matched parameters. There was a trend in increased grade I/II skin toxicity in the boost group (Table) but no difference in grade III toxicity. Rate of pCR did not differ between the boost and no boost groups (17.1% vs. 15.8%, p=0.83) but T downstaging was greater with RT boost (76.3% vs. 51.3%, p<0.001). Conclusions: CRT with radiation dose escalation in LARC improves T downstaging without significantly increasing toxicity. This approach could improve resectability of more advanced tumors, particularly within the distal rectum. Parameter Boost (n=76) No boost (n=76) P value Gender (M) 49 (64.5%) 50 (65.8%) 0.87 Age (years) 57.1 ± 13.0 55.9 ± 11.7 0.54 Procedure LAR: 19 (25.0%) Same N/A CAA: 36 (47.4%) APR: 21 (27.6%) Initial T stage T2: 2 (2.6%) Same N/A T3: 71 (93.4%) T4: 3 (4.0%) Same N/A Initial N stage N+: 34 (44.7%) Same N/A Grade I/II Skin 53/76 (69.7%) 34/63 (54.0%) 0.06 Radiation toxicity Nausea 21/76 (27.6%) 12/63 (19.0%) 0.24 Diarrhea 44/76 (57.9%) 41/63 (65.1%) 0.39 Pain 14/76 (18.4%) 8/63 (12.7%) 0.36 Abbreviations: APR, abdominoperineal resection; CAA, proctectomy with coloanal anastomosis; LAR, low anterior resection.
Lung volume reduction surgery for a decompensated COPD – Case report
Authors: Cornel Petreanu, Cornel Savu, Nicolae Galie, Gina Ciolan
Journal: European Respiratory Journal (2011)

Introduction:  Lung surgery reduction is a known method which can improve the quality of life for certain COPD. Parts of the lung that are particularly damaged by emphysema are removed, allowing the remaining, relatively good lung to expand and work better.   Clinical features:  The work presents a patient with stage IV COPD admitted in our service after a severe decompensation. Comorbidities: severe obesity, chronic coronary ischemic disease and diabetes, left pneumotorax (secondary a giant bulla of emphysema) and infectious pneumonia. We maintained the antibiotherapy and we aplied an anterior pleurotomy on the left medioclavicular line. The evolution was initially good with suppression of the tracheotomy9s canule and of the pleurotomy9s tube in five days.   Surgery:  48 hours after removing the chest tube, the pneumotorax recedived and we decided the surgery treatment. We performed the resection of the giant bulla and mechanical pleurodesis.  After opening of the bulla we used a fold of visceral pleura to covering the cavity in separated points.   The outcomes:  The postoperator evolution was very good with spontan closure of the traheostomy and with ablation of the tube in a week.The respiratory test indicated a improved with 15%.   Discussion  Lung volume reduction surgery is indicated in selected cases, after surgery both lung functional tests and clinical performance of the patient beeing improved.
Sunitinib in non-clear cell renal cell carcinoma (ncc-RCC): A phase II study
Authors: E. R. Plimack, E. Jonasch, B. N. Bekele, L. A. Smith, J. C. Araujo, N. M. Tannir
Journal: Journal of Clinical Oncology (2008)

5112 Background: Sunitinib has been shown to produce high response rates (RR) with improved progression-free survival (PFS) in pts with clear-cell RCC (cc-RCC). Retrospective data suggest sunitinib may be effective in ncc-RCC. Methods: This single-arm trial used a 2- stage design with 20 pts accrued during the first stage, with planned accrual of 40 additional pts if the observed RR is ≥ 10% or if > 25% of pts are progression-free at 12 wks. Eligibility criteria required pts to have ncc-RCC, PS 0–2, measurable disease and a maximum of 2 prior regimens. Patients with brain metastases were allowed to enroll. Sunitinib was given at 50 mg daily, 4 wks on, 2 wks off. RR and PFS are primary endpoints. Results: Between 3/2007 and 12/2007, 20 pts were enrolled (papillary 13, unclassified 3, chromophobe 1, translocation 1, collecting duct 1, sarcomatoid 1). Sixteen pts (80%) had prior nephrectomy and 5 pts (25%) received prior systemic therapy for advanced disease. Twelve pts (60%) had poor-risk features defined as ≥ 3 of the following: < 1 year from initial diagnosis to initiation of therapy, KPS ≤ 70%, anemia, elevated serum LDH, elevated corrected serum calcium, or ≥ 2 metastatic sites. Seventeen pts are evaluable for toxicity and response. Median follow-up duration is 15 wks (range 4–34). Common (> 2 pts) grade 3/4 adverse events include fatigue (4 pts), neutropenia (3 pts) and stomatitis (3 pts). Two pts required 25% dose reduction for fatigue. To date, there are no objective responses. Nine pts had progressive disease at or before completion of cycle 1. The remaining 8 [47%] pts (6 papillary, 1 chromophobe, 1 collecting duct) had stable disease. To date only one of these has progressed. Another patient with stable disease came off study for toxicity. Median PFS = 48 days [95% CI; 38-NE]. Four pts died at 28, 44, 44 and 103 days after initiation of therapy. Nine pts continue to receive therapy on protocol (6 with SD, 3 too early to evaluate). In this preliminary analysis, 6/20 pts (30%) are progression-free at 12 wks (95% CI, 12- 54); therefore accrual will continue to a total of 60 pts. Conclusions: In this phase II trial of sunitinib in ncc-RCC, preliminary results are disappointing in terms of RR and PFS. These may be partly explained by the high percentage of pts with poor-risk features. Accrual continues and updated results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer
Radiograph-Negative Lateral Ankle Injuries in Children
Authors: Kathy Boutis, Amy Plint, Jennifer Stimec, Elka Miller, Paul Babyn, Suzanne Schuh, Robert Brison, Louis Lawton, Unni G. Narayanan
Journal: JAMA Pediatrics (2016)

IMPORTANCE Lateral ankle injuries without radiographic evidence of a fracture are a common pediatric injury.These children are often presumed to have a Salter-Harris type I fracture of the distal fibula (SH1DF) and managed with immobilization and orthopedic follow-up.However, previous small studies suggest that these injuries may represent ankle sprains rather than growth plate fractures.OBJECTIVES To determine the frequency of SH1DF using magnetic resonance imaging (MRI) and compare the functional recovery of children with fractures identified by MRI vs those with isolated ligament injuries. DESIGN, SETTING, AND PARTICIPANTSA prospective cohort study was conducted between September 2012 and August 2014 at 2 tertiary care pediatric emergency departments.We screened 271 skeletally immature children aged 5 to 12 years with a clinically suspected SH1DF; 170 were eligible and 140 consented to participate.INTERVENTIONS Children underwent MRI of both ankles within 1 week of injury.Children were managed with a removable brace and allowed to return to activities as tolerated. MAIN OUTCOMES AND MEASURESThe proportion with MRI-confirmed SH1DF.A secondary outcome included the Activity Scale for Kids score at 1 month. RESULTSOf the 135 children who underwent ankle MRI, 4 (3.0%;95% CI, 0.1%-5.9%)demonstrated MRI-confirmed SH1DF, and 2 of these were partial growth plate injuries.Also, 108 children (80.0%) had ligament injuries and 27 (22.0%)had isolated bone contusions.Of the 108 ligament injuries, 73 (67.6%) were intermediate to high-grade injuries, 38 of which were associated with radiographically occult fibular avulsion fractures.At 1 month, the mean (SD) Activity Scale for Kids score of children with MRI-detected fibular fractures (82.0%[17.2%]) was not significantly different from those without fractures (85.8% [12.5%]) (mean difference, -3.8%; 95% CI, -1.7% to 9.2%).CONCLUSIONS AND RELEVANCE Salter-Harris I fractures of the distal fibula are rare in children with radiograph fracture-negative lateral ankle injuries.These children most commonly have ligament injuries (sprains), sometimes associated with radiographically occult avulsion fractures.Children with fractures detectable only by MRI had a comparable recovery with those with sprains when treated with a removable ankle brace and self-regulated return to activities.This work has the potential to simplify the care of these common injuries, safely minimizing the inconveniences and costs of overtreatment.