tbuckley/cabot-search huggingface dataset:
Medicines use review in renal cancer: How are we doing? What could we do better?
Authors: Nicholas James MacLeod
Journal: Journal of Clinical Oncology (2012)

458 Background: Following guidance from the National Institute for Clinical Excellence (NICE), sunitinib became available for use in the West of Scotland (WOS) in March 2009 as first line treatment for patients with advanced renal cell carcinoma (RCC) who were suitable for immunotherapy and had a performance status (PS) of 0 or 1. We performed a Medicines Use Review of sunitinib in patients who commenced treatment between March 2009 and February 2010. Data were analysed in April 2011. Methods: Patients were identified from an electronic prescribing database. A mixture of prospective and retrospective data were collected using case notes and electronic patient records. Results: 89 patients commenced treatment during this time. 16 patients were excluded as they were enrolled in clinical trials. 73 patients were included in the study. 54 (74%) were male. At the time of analysis, 31 patients were alive. Mean age at first cycle was 62 years. 22 (30%) patients had non clear cell pathology (NCC). 59 (81%) patients had prior nephrectomy and 31 (42%) had prior drug therapy. Median duration of therapy was 6.9 months. Median survival (MS) was 14.4 months (15.1 months for clear cell patients and 8.1 months for non clear cell patients). The most common toxicities (grade 2 or above) were cutaneous, diarrhoea and fatigue. PS was not documented for 43 patients. Where PS was documented, 13 were PS 0, 13 were PS 1 and 4 were PS 2. 32 patients required at least one dose reduction. Three patients later had their dose re-escalated. Conclusions: Our survival figures are lower than those reported in the pivotal trial 1, but comparable to the expanded access programme 2. This may reflect the high proportion of our patients with NCC and with prior treatment. 1. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cancer. J Clin Oncol 27 (22): 3584-90, 2009. 2. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded access trial. Lan Oncol 10: 757-63, 2009.
Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations.
Authors: Fatima H. Karzai, Bamidele Adesunloye, Yangmin M. Ning, Ravi Amrit Madan, James L. Gulley, Andrea Borghese Apolo, Melony A. Beatson, Anna Couvillon, Nancy Harold, Howard L. Parnes, Philip M. Arlen, John Joseph Wright, Clara Chen, Nancy Ann Dawson, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2013)

128 Background: We have recently completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P). Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90410 trials we attempted to contrast and compare our studies with the failed phase III trials. Methods: Among the first 52 pts on the ART-P, 3 received L 15 mg daily, 3 had 20 mg daily, and the rest had 25 mg daily for 14 days of every 21−day cycle (C). We later enrolled 11 more pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily throughout each C. Pegfilgrastim was given on day 2. Patients on CALGB 90410 received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and on MAINSAIL received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90410 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: Median number of Cs in ART-P was 16 (3−38). PFS was 22 months and median OS has not been reached. Pts with measurable disease had 1 CR and 25 PR (86.7% RR). Two patients (3%) had deep vein thromboses. Of 1,219 cycles given, 14 cycles were complicated by febrile neutropenia (FN) (1.1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90410 trial, median OS was 22.6 months with median PFS of 9.9 months. Median number of Cs was 8, and 19 pts developed thromboses/emboli (3.6%). In addition, 7% of patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allows the ART-P combination to be given for more cycles than were given in MAINSAIL and CALGB 90401 potentiating a longer PFS, RR and possibly OS with an improved toxicity profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
Absence of human papilomavirus (HPV) in tissues samples of lung adenocarcinoma regardless of mutations in epidermal grown factor receptor or response to erlotinib: Data from the University Hospital Arnau de Vilanova of Lleida, Spain.
Authors: D. Marquez-Medina, M. Taberner Bonastre
Journal: Journal of Clinical Oncology (2011)

e21124 Background: Not all non-small cell lung cancers (NSCLC) are related with smoke exposure. The relationship between human DNA papillomavirus (HPV) and the development of NSCLC is discussed since 1979. Literature reports a 10-20% rate of HPV infection in NSCLC samples, but it percentage widely ranges from 0’2 to 80% according several variables. 1) Cytology or sputum samples from NSCLC generally yield a poorer rate of HPV detection than tissue biopsies of the same population (2’8 vs. 20%); 2) The rate of HPV infection is considerably lower in Occident than in Oriental countries (10 vs. 35’7%); and 3) HPV infection seems to be more frequent in specific NSCLC subtypes. Oriental nonsmoker women with lung adenocarcinoma, the same population that exhibit a higher incidence of activating mutations of the epidermal growth factor receptor (EGFR), present a higher rate of infection. In this sense, a recent publication reports that HPV infection is more common in samples from lung adenocarcinomas that respond to gefitinib, a drug that only works in presence of EGFR mutations. Anyway, a direct relationship between HPV infection and mutations of EGFR has not been explored yet in NSCLC. Methods: We analyzed 43 formalin-fixed, paraffin-embedded samples of NSCLC. Genomic DNA was isolated with the DNA easy tissue kit (Qiagen GMBH, Hilden, Germany), andlinear array HPV genotyping test (Roche, Switzerland) was used to amplify HPV DNA from 37 genotypes including 13 high risk HPV genotypes. This test amplifies target DNA by PCR and nucleic acid hybridization. Differences according, smoke habit, gender, response to erlotinib and presence of mutations of EGFR mutations were evaluated. Results: Samples from 22 male and 21 female patients were analyzed. Eleven of them exhibit mutations of EGFR, and 24 of them received erlotinib in their treatments. DNA of VPH was detected in one patient only. Conclusions: No relationship between HPV infection and NSCLC can be confirmed in our data. Gender, smoke exposition, histology, presence of EGFR mutation or response to erlotinib did not influence the rate of HPV detection.
Assessing the value of weekly full blood counts (FBC) in patients with advanced serous gynecologic cancers receiving weekly carboplatin/paclitaxel (wCP) chemotherapy.
Authors: D. Ulahannan, G. J. S. Rustin, M. Hall
Journal: Journal of Clinical Oncology (2011)

5083 Background: Weekly paclitaxel (wP) with 3 weekly or weekly carboplatin (wC) are the most active regimens in serous gynaecological cancers (Van der Berg 2009, Katsuma 2009). wCP has also been shown to have fewer adverse effects and is now regularly used to treat such patients who traditionally have FBC prior to every infusion (d1, d8, d15). A retrospective analysis was conducted to quantify the incidence of thrombocytopenia and neutropenia (N) in patients deemed ‘well enough’ medically to receive their wCP. Methods: 26 patients (22 ovary, 4 serous endometrial) treated with wCP for advanced serous gynaecological cancers over 2 years were identified from the chemotherapy database. FBCs for each planned wCP infusion were documented. Treatment was administered if on medical review they were deemed ‘well’ enough, platelets were >100 x 109/L and neutrophils were >1.0 x 109/L. Results: 208 infusions of wCP were planned, 24 patients received wC (AUC 2-3, calculated GFR) with wP (80-90 mg/m2), two had wP 80mg/m2, one with 3 wC (AUC 6). Patients had received between 0 - 6 (median 2) previous lines of chemotherapy. The mean number of weekly treatments given was 8 (range 1-12). 14 infusions were omitted for reasons unrelated to haematological parameters and so excluded from study sample. 194 planned infusions of wCP were included for assessment of influence of FBC on intention to treat. Neutropenia (Grade 3 CTC, 0.5-1.0 x 109/L) occurred in 3 patients [5/194 or 2.5%]; one receiving wC AUC 3 had G3 N at d8 every cycle (3 /194), 2 receiving wC AUC 2.5 had G3 N (0.9 and 0.7 x 109/L) at d15 of one cycle. Thrombocytopenia (all Grade 2 CTC) was recorded on 3 occasions [3/194 or 1.5%] in 2 patients, both at d1, one went on to receive d1 treatment but stopped at d8 for PD and lower platelets (51 x 109/L). The other’s wCP was delayed 2 weeks and wC dose reduced to AUC2 (from AUC 2.5). Conclusions: The incidence of thrombocytopenia and neutropenia detected on routine day 1, 8 and 15 FBC is less than 3% in ‘well’ patients on wCP. This suggests that ‘well’ patients only require bloods on d1 of each cycle of wCP. Excluding d8, d15 bloods will ensure more efficient delivery of wCP and will be more cost effective.
Long-term follow-up of treatment of acute malignant colorectal obstruction with self-expanding metallic stent as a preoperative brigde to surgery.
Authors: R. Querol, C. Pericay, A. Pisa, E. Dotor, J. Perendreu, J. Falcó, I. Moya, M. Pampols, M. Seguí, E. Saigí
Journal: Journal of Clinical Oncology (2010)

e14098 Background: Ten to thirty percent of colonic cancers are diagnosed at acute colic obstruction stage. Self- expanding metallic stents (SEMS) for preoperative bridge to surgery treatment of obstructive colorectal cancer has been used with good short-term results. However, long-term prognosis is still controversial because SEMS portend adverse oncologic outcomes with increased risk of metastasis. Methods: We retrospectively reviewed no metastatic patients who had been treated with SEMS for obstructive colorectal cancer as preoperative bridge to surgery from May 2001 to October 2008. Results: 45 patients (pts.) were included: 32 men and 12 women with median age of 76 (42-90 years). Mean time interval between SEMS insertion and surgery was 6.33 days (1-20 days). Mean time of hospitalization was 18.82 days (1-44 days). According to the sixth edition of American Joint Committee on Cancer one pt. (2.2%) was stage I, 17 pts (37.7%) stage II and 27 pts (60%) stage III. In stage I, 1 pt (100%) didn't receive chemotherapy as adjuvant treatment. In stage II, 5 pts (29.4%) didn't receive chemotherapy, 8 pts (47%) were treated with MAYO, 2 pts (11.7%) with capecitabine and 2 pts (11.7%) with Folfox. In stage III 5 pts (18.5%) didn't receive chemotherapy, 12 pts (44.4%) were treated with MAYO, 3 pts (11.1%) with capecitabine and 7 pts (25.9%) with Folfox. Follow-up: 16 pts ( 3 pts with stage II and 13 pts with stage III) had metastatic disease (36.8% lung, 26.3% peritoneal, 21.05% liver, 10.5% retroperitoneal lymph nodes, 5.2% ovarian). PFS was 6.7 years and median OS was 7.77 years, with a 5-year survival rate of 70%. Conclusions: SEMS insertion as a “bridge to surgery” have good postoperative results and have no disadvantages in long-term prognosis No significant financial relationships to disclose.
STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS
Authors: Takuji Shionoya
Journal: The Journal of Experimental Medicine (1927)

Thrombus formation has been studied in normal rabbits with an experimental method of establishing extracorporeal circulation. In the normal animal circulation in the extracorporeal loop usually ceases in from 6 to 10 minutes, or at most, in very large and vigorous animals, in 25 minutes.(1) Cessation of the circulation is due most frequently to obstruction of the venous cannula (sometimes of the arterial cannula) by a mass of white thrombi and secondary fibrin formation around it. The site of the clot is determined somewhat by the swiftness of the blood stream. In the collodion tube red mural thrombi are obtainable as a rule. They are flat and present a wide base resting on tiny white thrombi. After the complete obstruction of the circulation, the blood in the apparatus clots very rapidly. When the obstruction occurs very quickly either in the arterial or venous cannula, or when the blood stream is very slow, the clotting in the loop may occur before platelets are laid down in large numbers or before the formation of the white thrombi is evident. Mixed thrombi are found in the jugular vein, and have their inception in the white thrombi, in the cannula or from the injured intima. They extend in the direction of the blood flow.
Differences in the clinical presentation, severity, and treatment outcome for symptomatic versus asymptomatic pulmonary embolism in cancer patients
Authors: G. V. Savla, G. Gladish, X. Zhou, S. Vadhan-Raj
Journal: Journal of Clinical Oncology (2008)

20688 Background: Pulmonary embolism (PE) is a common complication in cancer patients (pts). However, the incidence and outcome of symptomatic (sym) versus (vs.) asymptomatic (asym) PE in cancer pts remains uncertain. The objectives of this study were to evaluate the frequency of sym and asym PE in cancer pts and to determine the differences in the pt characteristics, treatment and the outcome between the two groups. Methods: Medical records of 55 consecutive cancer pts who were newly diagnosed with PE at MD Anderson Cancer Center during early 2006 were retrospectively reviewed and followed for one year from the time of PE diagnosis. Mastora’s PE Score System [Eur Radiol (2003)13:29–35] was used to evaluate the PE burden. All statistical analysis was done using SAS software. Results: In cancer pts, asym PE was more commonly seen than sym PE (56% asym vs. 44% sym), predominantly affecting males (61% vs. 38%, p= 0.08). Asym PE was more commonly diagnosed in the outpatient setting (90% vs. 54%, p =0.0023) on routine CT scan of the chest done for cancer staging (90% vs. 33%, p<0.0001). The burden of PE, as calculated by Mastora’s PE Score System was not significantly different between the two groups (see Table). All PE pts were treated with anticoagulation treatment except for five asym pts who did not receive treatment due to contraindications (e.g. bleeding). At one year follow-up, the all cause mortality in both the groups was not statistically different (48% vs. 56%). We, therefore, examined for the presence of underlying lung disease to explain the differences in the clinical presentation of PE. Interestingly, sym PE pts had significantly greater incidence of underlying non-malignant (e.g. pneumonia) lung disease (71% in sym vs. 32% in asym, p=0.0045) which might explain for the symptoms at presentation in this group. Conclusions: Our findings underscore the importance of detection of asym PE on routine staging CT scans and its appropriate treatment in cancer pts. Region Asym (n = 31) mean ± Std Sym (n = 24) mean ± Std Central 11.7 ± 14.9 9.2 ± 14.1 Peripheral 14.7 ± 14.1 11.9 ± 12.4 Global 13.7 ± 13.0 11.0 ± 12.5 No significant financial relationships to disclose.
How can we prove that a preventive measure in elite sport is effective when the prevalence of the injury (eg, ACL tear in alpine ski racing) is low? A case for surrogate outcomes
Authors: Josef Kröll, Jörg Spörri, Sophie Elspeth Steenstrup, Hermann Schwameder, Erich Müller, Roald Bahr
Journal: British Journal of Sports Medicine (2017)

When dealing with small cohorts, as is typical in elite sport, the well-known four-step ‘sequence of prevention’ described by van Mechelen  et al 1 (figure 1) potentially represents a vicious circle: When introducing a prevention measure, an otherwise reasonable call for targeting specific subgroups (ie, relevant groups of athletes, injury locations and specific injury causes) may undermine study power, breaking down an already-small baseline cohort into undersized pieces. Consequently, statistical testing becomes impossible.



Figure 1 
The four-step ‘sequence of prevention’ as described by van Mechelen  et al .1



To illustrate the problem we (1) discuss a recently implemented preventive measure in alpine ski racing as an example, (2) highlight the influence of sample size and effect size on study power and the possibility for statistical hypothesis testing and (3) provide a solution to increase study power for comparable injury prevention initiatives in elite sports.

In elite alpine ski racing, we recently tested potential preventive measures (eg, ski equipment changes) that target a specific body part (eg, knee/ACL injuries),2 their specific mechanisms (eg, aggressive ski–snow interaction driven by the skiing equipment)3 4 and specific disciplines (eg, different ski alterations in downhill, super-G and giant slalom).5 Based on this research process,6 the International Ski Federation (FIS) introduced new equipment rules for the 2012–2013 season.

The effect of these changes was assessed by repeating step 1 …
Decision of palliative chemotherapy in late-stage cancer: The doctor-patient relationship and the decision-making process as seen by an oncologist.
Authors: Florian Scotte, Marie Pechard, Ivan Krakowski, Christophe Tournigand, marcel-Louis Viallard
Journal: Journal of Clinical Oncology (2016)

48 Background: We conducted a literature review on the administration of palliative chemotherapy in cancer patients at advanced stage. We wondered about ethical tensions encountered by the oncologists during the decision process to meet or not the patients' demand to have access to a palliative chemotherapy at a late stage of the disease. Methods: We conducted a multicenter, qualitative study of senior oncologists in university hospitals and cancer centers in France, by carrying out interviews with eleven oncologists. Results: The study are consistent with the literature showing that factors are in favor of treatment continuation: the patient's age, his desire to continue treatment and his life expectancy. The decision making process of chemotherapy discontinuation is marked by uncertainties, personal representations of the doctor and subjectivity in front of the objective facts that could make this decision difficult. The working conditions in cancer care and the valuation of the chemotherapy prescription can impact the decision. The constant medical progress in oncology make more complex the decision of stopping specific treatments. This study showed the singularity of the doctor-patient relationship in oncology. This can explain the difficulty to stop chemotherapy. Conclusions: The oncologist can use the collegiality which are necessary for decision to limit specific treatment. The objective is to propose the adequate care to the patient in all its dimensions. Some actions can be proposed to improve our practice: early use of palliative care for patients, analysis of practices and training to deal with uncertainty and the limits of possibilities in clinical practice.
Long-term survival of patients with colorectal liver metastasis (CLM) receiving liver resection (LR): Survival and prognostic factors (PF) of 257 patients
Authors: N. Demmel, C. Saebisch, C. Nibler, N. Nüssler, M. Karthaus
Journal: Journal of Clinical Oncology (2008)

4079 Background: LR is currently the curative approach of CLM. Validated PF are helpful for decisions regarding primary surgery and chemotherapy of CLM. The question of adjuvant ctx after LR is still open. The aim of the study was to analyze PF for survival after resection of CLM. Methods: Consecutive pts with CLM and LR were studied. Between 01/1990 and 12/2003 a total of 257 pts with CLM (colon 121, rectal ca 136) received LR in a Munich CRC center. 106 pts had synchrone and 151 had metachrone CLM. After LR of CLM 155 (60%) out of 257 received Ctx. Results: Post-op mortality was 1.2% (3/257). Median survival after LR was 55.6 mo with a 5-ys of 47.1% and a 10-ys survival of 18.1 %. Median (55.8 vs 55.7 mo) and 5-ys OS (46.3 vs 47.6 mo) did not differ between syn- or metachrone LM. Initial LN status of pts with CLM was pN0 in 115/256 pts, while this was pN1 in 67 pts, pN2 in 43 and pN3 in 28. LN-status was associated with inferior OS. Median OS was 64.7 mo in pN0, while this was 53.8 in pN1, 41.2 in pN2 and 32.0 mo in pN3 pts with a 5-ys survival of 58% for pN0, 46.7% for pN1, 42.9% for pN2 and 21.4% for pN3 respectively (p=0.0025). A R0 LR of CLM was performed in 167/256, while this was R1 in 20, R2 in 11 and Rx in 59 pts. Pts with R0 resection had an OS of 65.4 mo, while this was significantly inferior in R1 (24.4 mo) and R2 resections (19.9 mo; p=0.0001). LM number (1 vs 2–3 vs >4) was associated with a worsening median (65.4 vs 48.1 vs 41.2 mo) and 5-ys survival (55.4 vs 37.9 vs 29.1 mo; p=0.0012). LM size ( <5 vs 5–10 >10 cm) was associated inversely with median (60.2% vs 42.9% vs 30.2%) and 5-ys OS (50.9% vs 39.8% vs 0%; p=0.0007). Adjuvant Ctx following LR improved median (63.6 vs 47.5 mo) as well as 5- ys OS (54.1% vs 39.1%). A total of 64 of 256 pts remained free of disease (med OS 136 mo) while 45 had new metachrone LM, 87 had LM and extrahepatic M and only 26 pts had a extrahepatic distant M. Conclusions: No difference in OS was observed between pts with syn- or metachrone CLM, while an increasing number and size of LM was associated with a worsening OS. Postoperative ctx after LR of CLM improved 5-ys survival and should be investigated in further trials. No significant financial relationships to disclose.
Incidence of methacronous cancer after total colectomy with ileorectal anastomosis or total proctocolectomy in classical FAP patients.
Authors: Samuel Aguiar, Paulo Roberto Stevanato, Fabio Oliveira Ferreira, Erika Maria Monteiro Santos, Ranyell Spencer Sobreira Batista, Ademar Lopes
Journal: Journal of Clinical Oncology (2014)

646 Background: Total proctocolectomy (TPC) with ileal pouch is considered the procedure of choice in classic familial adenomatous polyposis (FAP), but total colectomy (TC) with rectal sparing can be performed in selected cases. The objective of this study is to determine and compare the incidence of methacronous cancer in the remanescent rectum in patients submitted to TPC or TC. Methods: We performed a retrospective analysis of 55 patients operated beteween 1992 and 2011. Patients were identified from 34 FAP families, registered at the AC Camargo Hereditary Colorectal Cancer Registry. Patients with attenuated FAP were excluded. The main endpoint was the occurence of cancer at the remanescent rectum. Results: Thirty seven patients were submitted to TPC and 18 to TC with ileo-rectal anastomosis. Among patients submitted to TPC, just one (2.7%) had methacronous adenocarcinoma just above the dentate line. Among patients submitted to TC with rectal sparing, 4 (22.2%) have another cancer at the remanescente rectum. This difference was statistically significant (0.035). The stage was initial in all cases, and all patients were submitted to salvage surgery. No deaths related to rectal cancer had occured. Conclusions: Surgical treatment of classical FAP still remains proctocolectomy with ileal pouch, whenever possible. Considering that methacronous cancer uses to be detected in initial stages, rectal sparing can be considered in very selected cases of classical FAP.