tbuckley/cabot-search huggingface dataset:
Combined versus sequential adjuvant therapy of biliary tract cancer: What is the best option?
Authors: Alessandra Cassano, Gian Carlo Mattiucci, Eleonora Cerchiaro, Vincenzo Pio Di Noia, Rosa Autorino, Laura De Filippo, Antonia Strippoli, Vincenzo Dadduzio, Sabrina Rossi, Mario Larocca, Marco Campitiello, Matteo Ramundo, Francesco Ardito, Michele Basso, Felice Giuliante, Vincenzo Valentini, Carlo Barone
Journal: Journal of Clinical Oncology (2015)

e15155 Background: Biliary tract cancers (BTC) are composed by a heterogeneous and rare group of malignant tumors with poor prognosis. Surgical resection is the only potentially curative treatment. Currently, the standard of the adjuvant therapy is not yet defined due to the low number of pts and the few phase II-III available studies. The objective of this single retrospective center study is to compare the addition of CT to concurrent chemoradiation therapy (CT-CCRT) in an integrated model versus concurrent chemoradiation therapy (CCRT) alone in adjuvant setting. Methods: We reviewed clinical data about 123 pts with intra and extra-hepatic BTC treated with radical resection followed by adjuvant therapy from 2003 to 2013 at our institution. We compared the group of pts treated with adjuvant FOLFOX 6 schedule for 3 cycles followed by RT with 5-FU or Gem and further 3 cycles of FOLFOX (CT-CCRT) with pts treated with the same RT associated with Gem or 5-FU (CCRT). Results: Complete follow-up was available in 80 pts. Forty seven pts had intrahepatic and 33 pts had extra-hepatic adenocarcinoma. Thirty eight pts received CT-CCRT and 42 received only CCRT. Median OS was 33 months in the CT-CCRT group compared to 25 months in the CCRT group (p = 0.04). Median DFS was 25 and 21 months in the CT-CCRT and CCRT group, respectively (p = 0.03). Survival benefit of CT-CCRT over CCRT was observed in positive lymph nodes and R1 resection group (microscopically positive margins) (p = 0.01). Conclusions: Our study, although the small sample size, suggests that the CT-CCRT could represent a better option for patients submitted to radical surgery for BTCs in terms of OS and DFS. High risk patients, with nodal disease and R1 resection, seem to obtain the major benefit from this approach of therapy. Nevertheless, further randomized trials studies are needed.
2016 update of the EULAR recommendations for the management of rheumatoid arthritis: a utopia beyond patients in low/middle income countries?
Authors: Durga Prasanna Misra, Vikas Agarwal, Aman Sharma, Anupam Wakhlu, Vir Singh Negi
Journal: Annals of the Rheumatic Diseases (2017)

We read with great interest the recently published recommendations by the European League against Rheumatism (EULAR) on the management of rheumatoid arthritis (RA).1 The EULAR recommendations, although primarily targeted towards European countries, are read and followed across the world including low/middle income nations. Consequently, we were disappointed to note that the updated guidelines recommend the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) immediately following failure of monotherapy with conventional synthetic DMARDs (csDMARDs) in those patients with poor prognostic factors such as seropositivity for rheumatoid factor (RF) or anticitrullinated peptide antibodies (ACPA), highly active disease or early radiographic joint damage (recommendation number 8).1 This is in contrast to the 2015 guidelines provided by the American College of Rheumatology (ACR) for the management of RA,2 which offer the option of either combining csDMARDs or using bDMARDs or tofacitinib (tsDMARD) following failure of methotrexate monotherapy in RA, irrespective of the presence or absence of such poor prognostic indicators. Early use of bDMARDs in the management of RA poses certain specific problems, as discussed below.

Rheumatoid arthritis is one of the …
Real-time central review: A report of the first 3,000 patients enrolled on the Children’s Oncology Group Renal Tumor Biology and Risk Stratification protocol AREN03B2.
Authors: Elizabeth Anne Mullen, James I. Geller, Eric J. Gratias, Elizabeth Jones Perlman, Peter F. Ehrlich, Geetika Khanna, Arlene Naranjo, Ying He, Thomas Edward Hamilton, Fernando Anthony Ferrer, Richard D. Glick, Kenneth William Gow, Douglas C. Barnhart, Jessica J. Kandel, Roshni Dasgupta, Fredric A. Hoffer, Sabah-E-Noor Servaes, Conrad Vincent Fernandez, Paul Edward Grundy, Jeffrey Dome
Journal: Journal of Clinical Oncology (2014)

10000 Background: The Children’s Oncology Group (COG) Renal Tumor (RT) Biology and Risk Stratification Protocol incorporates real-time central review to direct risk stratification and enrollment on COG therapeutic studies. We assessed the feasibility of the real-time central review process and its impact on the accuracy of risk stratification. Methods: 3,000 patients were enrolled on AREN03B2 between 2/2006 and 1/2012, with submissions from 214 COG institutions. Eligible diagnoses included any RT and extra-renal Wilms tumor or non-CNS rhabdoid tumor. Enrollment on AREN03B2 was required to enroll on a RT treatment study. Submission of pathology slides, radiology images, operative reports, and tumor and blood for analysis was required within 7 days of surgery to meet enrollment deadlines stipulated by the therapeutic studies. Central pathology review for histology and stage, radiology review for presence of bilateral lesions and pulmonary metastases, and surgical review for operative stage were completed electronically by a panel of expert reviewers. An initial risk assignment (IRA) was made by the study chairs based on the multidisciplinary central reviews. Results: 2,913/3,000 met all eligibility and submission requirements. The median time from enrollment to IRA was 8 days. 1,205 discrepancies between central and institutional review potentially impacting IRAs were observed; including differences in initial histology in 253 unilateral and 69 bilateral tumors, pathologic staging of 294 tumors, diagnostic imaging of 92 bilateral cases and 112 cases of pulmonary metastases, and the surgical review of 244 cases of rupture and 141 instances of node sampling. Conclusions: Real time central review is feasible in a large multi-center study. Discrepancies between local and central risk stratification were identified in a substantial number of participants. Communication of these findings in real time supported increased accuracy of enrollment on appropriate clinical trials and strengthened the comprehensive annotation of a rich RT biorepository. Expansion of this process to other pediatric tumor registry protocols should be strongly considered.
Statistical Methods in the <i>Journal</i> — An Update
Authors: Yasunori Sato, Masahiko Gosho, Kengo Nagashima, Sho Takahashi, James H Ware, Nan M Laird
Journal: New England Journal of Medicine (2017)

The authors surveyed the types of statistical methods used in the Journal during 2015. Investigators used a greater variety statistical methods, and the methods were more sophisticated than those used in earlier epochs.
A randomized, multicenter phase II study investigating additional weekly cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: Reporting on the efficacy.
Authors: Michel M van den Heuvel, Andrew D. Vincent, Wilma Uyterlinde, Joachim Aerts, Fredirike Koppe, Henk Codrington, Peter W.E. Kunst, Edith Dieleman, Paul van de Vaart, Marcel Verheij, Jose Belderbos
Journal: Journal of Clinical Oncology (2012)

7019 Background: Modest benefits from concurrent chemoradiotherapy (CRT) in patients with locally advanced NSCLC warrant more effective treatment regimen. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. Feasibility data and toxicity have been published previously. We report treatment outcome of a multicenter phase II study of the combination of high dose accelerated RT and daily dose cisplatin with or without weekly cetuximab. Methods: Patients with locally advanced NSCLC received accelerated RT (66 Gy in 24 fractions) and concurrent daily cisplatin (6 mg/m 2 ) with (Arm A) or without (Arm B) additional weekly cetuximab (400 mg/m 2 loading dose one week prior to the RT start followed by weekly 250 mg/m 2 ). The Objective Local Response Control (OLRC) was determined at 6 and 24 weeks after treatment using response evaluation criteria in solid tumours criteria. Results: Between Feb 2009 and May 2011, 102 patients were included. Median follow-up was 13 months. Patients and tumor characteristics are shows in the Table. Stage distribution was: II (8%), IIIa (51%), and IIIb (40%). The CRT was well tolerated. The OLRC at 24 weeks was 79% in Arm A and 80% in Arm B. The one-year progression free survival and overall survival were 58% (45%-76%) and 76% (64%-91%) for Arm A and 49% (35%-68%) and 72% (58%-89%) for Arm B respectively. Conclusions: The addition of cetuximab to low dose cisplation CRT does not improve OLRC in an unselected patient cohort but data on longterm disease control and survival are to be awaited. [Table: see text]
Persistance of residual vein thrombosis after an episode of deep vein thrombosis of the lower limbs and the risk of new cancer and cardiovascular disease
Authors: F. Fulfaro, S. Siragusa, R. Anastasio, A. Malato, A. Casuccio, C. Arcara, G. Badalamenti, M. Valerio, I. Abbene, N. Gebbia
Journal: Journal of Clinical Oncology (2006)

8531 Background: In patients with a first episode of idiopathic or provoked Deep Vein Thrombosis (DVT), the presence of Residual Vein Thrombosis (RVT), detected by UltraSonography (US) at the 3rd month from the index DVT, is an independent risk factor for developing recurrent Venous Thromboembolism (VTE) in the subsequent 2 years. Its absence can safely permit to stop Oral Anticoagulants (OA). At the present, it is unknown whether RVT may also identify patients at increased risk for developing cancer and/or cardiovascular disease (CD). In patients with previous DVT of the lower limbs, we conducted a prospective study for evaluating the correlation between RVT findings and the risk of new cancer and/or CD. Methods: Three hundred-forty-five patients, with a previous episode of idiopathic or provoked DVT, were evaluated; presence/absence of RVT was detected at the 3rd month of OA and patients managed consequently. In the present study, the incidence of VTE recurrence, cancer and new CD was evaluated in the subsequent 3 years after the index DVT. The Kaplan-Meyer curve and the Breslow test has been used for the statistical comparison among groups. Results: The results among the 3 groups are listed in the Table. Patients without RVT had a significant reduction in recurrent VTE and new cancer in comparison to patients with RVT; they also showed a not significant trend in the reduction of CD; these data are applicable in patients with idiopathic or provoked index DVT. In patients with RVT, the advantage of prolonging anticoagulation over 12 months (Group A1) is lost at the end of the treatment. Conclusions: US-detected RVT, at 3rd month from the index DVT, is an independent risk factor for recurrent VTE and cancer; this risk remains over a period of 3 years, independently whether index DVT was idiopathic or provoked. In these patients, the advantage of indefinite anticoagulation should be assessed in properly designed study. [Table: see text] No significant financial relationships to disclose.
ESTUDIO COMPARATIVO DE PÉRDIDA DE PESO A CORTO PLAZO ENTRE TRATAMIENTOS ENDOSCÓPICOS DE LA OBESIDAD. RESULTADOS PRELIMINARES
Authors: E Espinet Coll, J Nebreda, C Vila, JA Gómez, A Juan-Creix, P Díaz, K Gunnard, D Irigoyen, S Bacchiddu
Journal: Endoscopy (2015)

En los últimos años se han desarrollado nuevas técnicas endoscópicas bariátricas como tratamiento coadyuvante a la intervención dietética y modificación psicoconductual en pacientes obesos.
Assessing the Effects of Psychotherapy
Authors: Rolf Sandell
Journal: Psychotherapy and Psychosomatics (1987)

The reverence of the experimental method in psychotherapy research, even where it is pointless or unwarranted, is taken as an instance of the rhetoric function of science. The distinguishing features of an experiment, manipulation and randomization, are explicated. The vital assumption of the effect of the experimental treatment being constant among subjects is demonstrated, and it is concluded that this assumption is unwarranted, on both theoretical and empirical grounds, as applied to psychotherapy.
Efficacy and safety outcomes in heavily pretreated patients (pts) with relapsed ovarian cancer (ROC) after single-agent trabectedin.
Authors: Vanda Salutari, Gabriella Ferrandina, Bruno Vincenzi, Marco Marinaccio, Emanuele Naglieri, Vera Loizzi, Silvia Carpano, Domenica Lorusso, Rosa Pasqualina De Vincenzo, Distefano Maria Grazia, Giulia Amadio, Giuseppe Tonini, Giovanni Scambia
Journal: Journal of Clinical Oncology (2013)

e16538 Background: Trabectedin is a marine-derived antineoplastic agent, initially isolated from the tunicate Ecteinascidia turbinata and currently produced synthetically. In combination with pegylated liposomal doxorubicin, trabectedin is approved in Europe for the treatment of pts with platinum-sensitive (PS) ROC. The aim of this multicenter, retrospective study was to evaluate the efficacy and safety of single agent trabectedin in the palliative treatment of heavily pretreated patients with ROC. Methods: Patients with measurable ROC and at least 2 prior treatments were eligible. Patients received single agent trabectedin (1.3 mg/m 2 , n = 56; 1.1 mg/m 2 , n=42) as a 3-hour i.v. infusion every 3 weeks. An analysis of the overall response rate (ORR; primary end point) as per RECIST, time to progression (TTP) and overall survival (OS) were performed. Results: Overall, 98 pts were enrolled: median age at diagnosis of recurrence was 53 years (range: 29-79). Forty-four pts (44.9%) were fully PS, while 23 (23.5%) were partially PS and 31 (31.6%) were platinum-resistant. Median number of previous chemotherapy regimens was 4 (range: 2-6). The ORR was 28.6% (5 complete and 23 partial responses); 32 pts (32.6%) experienced stabilization of disease, which lasted ≥6 months in 2 pts, while 38 (38.8%) pts progressed during treatment. The ORR was higher in PS pts (38.6%) compared to partially PS (26.1%) and platinum resistant cases (16.1%), although the statistical significance was not reached (p=0.071). No difference in the ORR was found according to number of prior treatments or trabectedin dose. After a median follow-up of 8 months, median TTP and OS were 5 and 13 months, respectively. The most common grade 3/4 toxicities were transient and non-cumulative anemia and neutropenia in 6.1% and 17.5% of cases, respectively. AST and ALT were increased in 7.1% and 13.3% of pts. Cardiac toxicity was documented in 4 anthracycline pretreated pts, of whom one died due to acute arrhythmia. Conclusions: Single agent trabectedin represents a valid approach in the palliative treatment of pts with heavily pretreated ROC with meaningful clinical benefit and acceptable and manageable safety profile.
Targeted therapies for the treatment of non-small cell lung cancer: Bull’s eye or missed target?
Authors: Shakun M. Malik, John R Johnson, Karen Bijwaard, Robert Becker, Patricia Keegan, Richard Pazdur
Journal: Journal of Clinical Oncology (2012)

3074 Background: Targeted drugs approved for advanced non-small cell lung cancer (NSCLC) include bevacizumab [(monoclonal antibody directed against vascular endothelial growth factor-A (VEGF-A)], erlotinib [(an epidermal growth factor receptor kinase (EGFR) inhibitor)] and crizotinib [(an anaplastic lymphoma kinase (ALK) inhibitor)]. The development programs for erlotinib and bevacizumab did not prospectively employ in vitro diagnostic tests to select patients (pts). Post-hoc exploratory analyses for bevacizumab based on VEGF-A levels have not identified subgroups with differential treatment effects: however for erlotinib, pts with activating EGFR mutations had greater improvement in overall response rates (ORR) and progression-free survival. Crizotinib is the first targeted therapy for NSCLC in which pts were selected using an analytically validated investigational test for ALK translocations. Crizotinib received accelerated approval on August 26, 2011 for the treatment of pts with locally advanced or metastatic ALK-positive NSCLC as detected by an FDA-approved test (Vysis ALK Break Apart FISH Probe Kit) that was approved by FDA on the same day. Methods: NDA file for crizotinib was examined. Results: Two single arm trials assessing efficacy of crizotinib monotherapy in ALK positive pts showed ORR of 61% and 50%. At FDA’s request, a cohort of 23 pts that tested negative for the ALK translocation evaluated showed ORR of 26%. Two additional pts had a single assessment and, if confirmed, the response rate would be 37% in this “marker negative” subgroup. Further exploration of this subgroup is a postmarketing commitment. Conclusions: Evaluation of target status (positive or negative) in all pts provides optimal information to guide clinical practice. As observed with crizotinib, responses may be observed in the “marker negative” subgroup. This unexpected finding may reflect the drug’s activity via alternate pathways, selection of a suboptimal biomarker for assessing ALK activation, or selection of a suboptimal cut-point for positive/negative. Accurate diagnostic tests will facilitate drug development with possible greater observed treatment effect and potentially smaller clinical trials.
Treatment Situation for Newly Diagnosed Multiple Myeloma (MM) Patients in Germany (GER)- First Results from a Representative Multicentre Treatment Survey.
Authors: Mathias R.F. Freund, W. Knauf, H. Goldschmidt, H. Einsele, M. R. Nowrousian, W. E. Berdel, W. Poenisch, C. Straka, L. Kellermann, S. Bammer, R. Angermund
Journal: Blood (2005)
Investigation of PARP1 as a therapeutic target in small cell lung cancer.
Authors: Lauren Averett Byers, Monique B. Nilsson, Fatemeh Masrorpour, Jing Wang, Lixia Diao, Vikas Bhardwaj, James Welsh, Luc Girard, Kevin R. Coombes, John N. Weinstein, Scott Michael Lippman, Bonnie S. Glisson, John D. Minna, John Heymach
Journal: Journal of Clinical Oncology (2012)

7096 Background: Small cell lung cancer (SCLC) is an aggressive malignancy that differs from non-small cell lung cancer (NSCLC) in its metastatic potential and response to treatment. To date, no molecularly-targeted agent has prolonged survival of SCLC patients. Using a proteomic approach, we previously identified high expression of the DNA repair protein poly (ADP-ribose) polymerase 1 (PARP1) in SCLC cell lines and tumors. Here we test in vitro sensitivity of SCLC to PARP inhibition or knockdown. Methods: Cell lines were treated with PARP inhibitor olaparib or AG014699 for 14d +/- chemotherapy. Relative cell viability was assessed by cell count. siRNA against PARP1 was compared with scrambled siRNA and mock transfected cells. To assess DNA repair, RAD51 foci were counted after 1µM or 5µM olaparib and after 8Gy irradiation (RT). Results: SCLC cell lines were highly sensitive to PARP inhibition by olaparib (IC50s &lt;0.5 µM for H69; ≤2µM in H524, H82, and H526) and AG014699 (IC50s &lt;0.5 µM for H82, H69, and H524; 2.2 µM for H526 and H841). In contrast, A549 (NSCLC) was resistant to both drugs (IC50s &gt;8µM). Because BRCA1/2 and PTEN mutations are associated with greater sensitivity to PARP inhibitors, we compared SCLC sensitivity with that of BRCA1-mutated (HCC1395) and PTEN-mutated (MDA-MB-468) breast lines. As expected, HCC1395 and MDA-MB-468 were sensitive to both PARP inhibitors. Remarkably, however, SCLC cell lines were as sensitive or more so. Combination of olaparib with topotecan or irinotecan (commonly used in SCLC) decreased tumor cell viability more than either agent alone (p &lt;0.03). Consistent with the drug studies, knockdown of PARP1 by siRNA decreased growth of SCLC compared with that of controls. RAD51 foci increased in SCLC after olaparib treatment (&gt;4-fold) and RT (&gt;18-fold). Conclusions: SCLC lines were as sensitive to PARP inhibition as BRCA1- or PTEN-mutated breast cancer lines. Moreover, PARP inhibition enhanced the effect of chemotherapy on SCLC lines. Increased formation of RAD51 foci in SCLC cells after olaparib or RT suggests a deficiency in homologous recombination that may account for the sensitivity to PARP inhibitors. These results support the investigation of PARP inhibition as a novel therapeutic approach in SCLC lung cancer.
A Health Questionnaire Based on Paper-and-Pencil Medium Individualized and Produced by Computer
Authors: John G. Mayne
Journal: JAMA (1969)

The relatively inexpensive mark-sense paper-and-pencil technique for administering a computer-generated and computer-processed health questionnaire is easy for patients to understand, simple to revise, and permits large-scale testing at low cost. The total questionnaire is designed to be administered in two or more portions or levels. Because each level after the first is a more detailed inquiry into positive responses made to questions of preceding levels, this multilevel approach permits the inquiry to be individualized to the patient. The questionnaires are generated from a question library, and the completed forms are read by an optical scanner. A summary of the patient's responses is printed for the physician's use.
Subtyping muscle-invasive bladder cancer to assess clinical response to trimodality therapy.
Authors: Jason A. Efstathiou, Ewan Gibb, David Tomoaki Miyamoto, Chin-Lee Wu, Michael Drumm, Jonathan Lehrer, Hussam Al-Deen Ashab, Nicholas Erho, Marguerite du Plessis, Kaye Ong, Akshay Bhat, Kent William Mouw, Elai Davicioni, William U. Shipley
Journal: Journal of Clinical Oncology (2017)

287 Background: Trimodality therapy with TURBT followed by chemoradiation is an acceptable alternative to cystectomy for muscle invasive bladder cancer (MIBC). Recently, genomic profiling has demonstrated MIBC can be divided into three or more subtypes with differing responses to chemotherapy, suggesting genomic subtype may impact therapeutic response. Here, we explore the utility of genomic information to better select patients for bladder-sparing trimodality therapy. Methods: Transcriptome-wide gene expression profiles were generated for 189 MIBC TURBT samples from patients undergoing trimodality therapy at the Massachusetts General Hospital. Of these, 108 passed microarray QC and 100 had complete clinical information. The patient tumors were classified as basal, basal claudin-low, infilrated luminal or luminal subtype. The subtype and the expression of a number of bladder cancer genes were assessed for their association with need for salvage cystectomy and for overall survival. Finally, transcriptome-wide differential expression analysis was used to explore gene set enrichment in trimodality therapy response groups. Results: Our chemoradiation cohort (n = 108) was classified into the four subtypes: basal (n = 45), basal claudin low (n = 13), infiltrated luminal (n = 17) and luminal tumors (n = 33). Survival analysis (n = 100) showed that patients of the luminal subtype trended to better overall survival, but did not reach significance (HR = 0.63, p = 0.1). Fewer patients with infiltrated luminal tumors (12%) required a salvage cystectomy compared to all other subtypes (34+/-1.5%, p = 0.08). We found high expression of BLACAT1 and NORAD (a lncRNA with a role in genome stability) correlated with worse (p = 0.01) and better prognosis (p = 0.008), respectively. Likewise, patients with high levels of the luminal-associated PPARG showed a significant increase in overall survival (p = 0.0002). Gene set enrichment revealed differential regulation of immune pathways in the trimodality therapy responders relative to the non-responders (p &lt; 0.05). Conclusions: Preliminary data exploring MIBC subtyping suggests the possibility of using genomics to predict response to trimodality bladder-sparing therapy.