tbuckley/cabot-search huggingface dataset:
Is there still place for endoscopic mucosal resection in patients with early oesophageal carcinomas?
Authors: D. Bogoevski, P. G. Schurr, A. M. Koenig, P. Busch, A. Kutup, J. R. Izbicki
Journal: Journal of Clinical Oncology (2009)

e15640 Background: The objective of this study was to investigate whether limited resection of the oesophagogastric junction can be successfully used in the treatment of the patients with early oesophageal carcinomas. Methods: A total of 111 patients with early oesophageal cancer (57 adenocarcinomas, 54 squamous cell carcinomas) had surgical resection with systematic lymphadenectomy (41 thoracoabdominal-TA, 52 transhiatal-TH and 18 with limited resection of the oesophagogastric junction- LROGJ). Results: In all patients, regardless from the surgical procedure, a complete resection (R0) was achieved. The median lymph node yield was significantly higher (p=0.0001) in TA patients (24 LN), compared with TH (14LN) and LROGJ (16LN). The median in hospital and ICU stay were shorter in patients with the LROGJ (12 and 2 days, respectively) compared with the TA (24 and 8 days) and TH patients (23 and 4 days). None of the 43 patients with high grade intraepithelial neoplasia (HGIEN) or oesophageal carcinoma limited to the mucosa had lymphatic spread, as compared with 15 of 68 (22.1%) with affection of the submucosa. Although lymph node metastases were usually limited to locoregional lymph node stations, two patients had metastases in distant lymph nodes (pM1a) The infiltration of the submucosa was accompanied with significant worsening of the overall survival (pT1a vs. pT1b; p=0.002). Multifocal neoplasia was detected in three patients with SCC HGIEN (30%) but not in AC HGIEN! Nine out of 44 (20.4%) patients with early SCC had multifocal neoplasia, compared to 6 out of 53 (11.3%) patients in AC (p=0.322). The sensitivity of the preoperative tumour dept staging (endoscopic ultra sound - EUS; and CT) was astonishing low (only 50% for cT1b), as was the specificity (66.7% for cT1a and only 87.5% for cT1b). On multivariate analysis, only histological tumor type (AC) was independent predictor of survival. Conclusions: Considering the limitations and pitfalls of endoscopic and classical resectional procedures, the quest for alternative and “patient tailored” treatment in patients with early oesophageal carcinoma carries on. A valuable alternative can be the limited resection of the oesophago-gastric junction under sparing of the healthy oesophagus and stomach. No significant financial relationships to disclose.
Diffuse follicle centre lymphoma presents with high frequency of extranodal disease
Authors: A. M. Wehbe, V. Neppalli, S. Syrbu, T. Knutson, D. Burns, J. Friedberg, B. K. Link
Journal: Journal of Clinical Oncology (2008)

19511 Background: Follicular lymphoma (FL) comprises about one third of non Hodgkins Lymphomas in adults. The WHO now recognizes Diffuse Follicle Center Lymphoma (DFCL) as an uncommon variant of follicular lymphoma. DFCL is characterized by distinct lack of follicle formation, and is composed of a diffuse proliferation of neoplastic, small cleaved follicular center cells and variable number of admixed centroblasts. Immunophenotypic data show that DFCL and FL are of identical phenotype, and are positive for follicular center cell markers CD10, BCL6 and BCL2. Little is described about the clinical presentation of this FL variant. In this study, we describe the clinical characteristics and presentation of DFCL, in light of an increase in the diagnostic recognition of this unusual entity. Methods: Patient data was compiled through medical record review of all newly diagnosed FL patients seen at University of Iowa Holden Comprehensive Cancer Center and The University of Rochester Wilmot Cancer Center between March 2004 and March 2007. Pathology was centrally reviewed. Results: One hundred fifteen patients with FL were identified. Five were recognized to have extra-cutaneous pure DFCL - grade 1 (4/5) and grade 2 (1/5), Ann Arbor stage 1 (2/5) and stage 4 (3/5). Three of the five were older than 75; 4 M and 1 F. FLIPI scores were 2, 3, 1, 1 and 4. Only one patient was anemic. LDH was elevated in 2 patients. Of interest, 4 of the 5 had extranodal disease at presentation (tonsil, cortical bone, bone marrow and spleen). Two of the patients with extranodal disease developed CNS complications within 1 year of presentation (thoracic cord compression and cerebral metastases). Four additional patients with FL were identified to have diffuse pattern in > 75% of the pathological sample, three of whom had extranodal disease at presentation. Conclusions: The DFCL variant of FL in this small series presents with more frequent extranodal involvement than expected for the follicular counterpart. Whether the diffuse morphology conveys a more aggressive biology of the disease is unclear and optimal management strategies cannot be determined until there are larger series with longer follow-up. No significant financial relationships to disclose.
Angiogenesis-related gene profile to predict outcome to multimodal therapy in advanced ovarian carcinoma.
Authors: J. Barriuso, M. Mendiola, A. Redondo, I. Sánchez-Navarro, A. Mariño-Enriquez, J. A. Fresno-Vara, E. Perez, A. Hernandez, E. Espinosa, D. Hardisson
Journal: Journal of Clinical Oncology (2010)

5078 Background: Management of advanced ovarian carcinoma (AOC) involves surgery in order to achieve surgical cytoreduction followed by platinum (C) – paclitaxel (P) chemotherapy. A complete clinical remission is achieved in 40% to 50% of patients. Parameters such as age, extent of residual disease after surgery, and the histopathological subtypes are imperfect predictors of response. Angiogenesis plays a major role in ovarian carcinogenesis and progression. The aim of this study is to build a profile able to predict clinical response to multimodal first-line therapy. Methods: 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a C plus P regimen were included. RNAs were collected from formalin-fixed paraffin-embedded AOC samples. Expression levels of 82 angiogenesis related genes were measured using quantitative real time polymerase chain reaction. Clinical response was evaluated using CT after the completion of multimodal therapy. Statistical analysis was performed using a regression method to generate multiple models based on the significant genes. The accuracy of the models was evaluated using Receiver Operating Characteristic (ROC) curves. The Akaike Information Criterion based selection was used to find the most accurate one. Results: The median age at diagnosis was 53 years (range, 21 to 82 years). All patients had advanced disease (FIGO stages III/IV). Most of them had FIGO stage III (51, 83.6%), grade 3 tumors (35, 57.4%), and serous histology (42, 68.9%). 52 patients (85.2%) achieved an initial response (complete response or partial response by RECIST criteria) to this therapy. We found an independent model able to predict response to therapy comprising 8 genes with an Area Under the Curve (AUC) of 0.955 (p < 0.001). Leave-one-out cross validation was applied to avoid overfitting of the model, obtaining a corrected AUC of 0.880, 95%IC: 0,776-0,985. Conclusions: It is possible to generate a predictive model of clinical response for ovarian cancer based on angiogenesis related genes using formalin-fixed paraffin-embedded samples. Although these results are promising, they should be validated prospectively in larger series of ovarian cancer patients. No significant financial relationships to disclose.
Signet ring cell cancer: Harbinger of doom?
Authors: Sharven Taghavi, Senthil N. Jayarajan, Adam Davey, Alliric Isaac Willis
Journal: Journal of Clinical Oncology (2012)

10 Background: Signet ring cell cancer (SRC) is associated with worse prognosis. However, studies in Asia have questioned this idea. Our aim is to determine differences in presentation and outcomes between SRC and gastric adenocarcinoma (AC) to establish if SRC conveys worse prognosis in the U.S. Methods: NCI SEER was used to analyze differences in presentation and outcomes of SRC and AC from 2004−2007. Results: 10,886 gastric cancers included 2,872 SRC and 8,014 AC. SRC presented younger (62.0 vs 68.9 years, p&lt;0.001) and less in males (53.7 vs 68.0%, p&lt;0.001). SRC were more likely Asian (16.5 vs 13.5%) or Hispanic (23.3 vs 14.9%) and less Black (10.7 vs 11.5%) or White (71.8 vs 74.1%); p&lt;0.001. SRC was more likely to be T-3 or T-4 (46.0 vs 33.8%), have nodal spread (72.5 vs 62.0%), and metastases (29.0 vs 24.1%); p&lt;0.001. SRC was more likely lower stomach (30.6 vs 24.6%) or body (30.8 vs 21.6%) and less upper stomach (24.7 vs 46.9%); p&lt;0.001. SRC more often overlapped regions (13.9 vs 6.9%, p&lt;0.001). SRC was associated with mortality (HR 1.07, CI 1.01−1.14, p=0.017) and decreased median survival (12.0 vs. 13.0 months, p=0.034). Multivariate analysis stratified by AJCC stage and radiation found SRC was not independently associated with mortality (HR 1.04, CI 0.98−1.11, p=0.195). Mortality was associated with age (HR 1.01, CI 1.01−1.01, p=0.001), Black race (HR 1.11, CI 1.02−1.21, p=0.013), and tumor grade ( table ). Survival was associated with Asian race (HR 0.88, CI 0.81−0.95, p=0.001) and surgery (HR 0.21, CI 0.19−0.22, p=0.001). Conclusions: In the U.S., SRC differs from AC in presentation with younger age, less male predominance, greater tumor extent, metastases, and Asian or Hispanic ethnicity. Survival for SRC is associated with Asian race and surgical resection. Overall, SRC survival is less than AC. However, adjusted for stage at presentation, SRC does not portend a worse prognosis. [Table: see text]
Expression profile of residual breast cancer after primary chemotherapy based on doxorubicin
Authors: M. A. Koike Folgueira, H. P. Brentani, D. F. Padrao, D. M. Carraro, M. L. H. Katayama, L. D. Mota, E. M. Barbosa, C. T. Oliveira, M. M. Netto, M. M. Brentani
Journal: Journal of Clinical Oncology (2005)

639 Background: Expression profile of the remaining malignant cells in breast cancer after the last cycle of primary chemotherapy (PCT) based on doxorubicin (AC) might help to identify a resistant phenotype. Methods: To analyse changes in gene expression in samples of primary breast tumors before and after systemic chemotherapy, ten pt (median age 46.5 years, 3 post-menopausal) clinically staged as II (n=2) or III (n=8) breast cancer were submitted to PCT, receiving at least 90% of the planned doxorubicin dose in a median interval of 66.5 days. Samples were obtained by tumor biopsy before PCT and after 4 courses of AC, upon surgical intervention. Surgery was performed at least 28 days after AC last course. All pts presented a tumor reduction according to RECIST. Samples were hand-dissected to eliminate non-tumoral tissue. RNA was extracted, amplified and gene expression analysed using a cDNA microarray plataform having 4608 genes. Results: One hundred and seven genes were found differentially expressed by both a permuted Student t test at a False Discovery Rate (FDR) level ≤ 0.001 and p≤0.05 by paired Student t test. Unsupervised hierarchical clustering employing 34 differentially expressed genes at FDR level < 0.001 and Bayesian Error Rate < 50% allowed a proper discrimination of 100% post treatment samples. The discriminators included genes up-regulated such as SEPT1, a member of GTPase family, a growth factor receptor (PDGFRL) implicated in transcapillary transport in tumors and Pumilio homolog1 (PUM-1), an essential protein for stem cell maintenance and self-renewal. Genes involved in proliferation were repressed including IRS1 (insulin receptor substrate-1), PTPRC (a regulator of citokyne receptor signaling), CORO1C (coronin) and CSE1L (CAS) which depletion leads to cell cycle arrest. Notably HMG2L1 (high-mobility group protein 2-like1) was also down regulated reflecting enhanced excision repair mechanism. Conclusion: Genes differentially expressed in residual breast cancer after PCT may potentially represent a signature profile for doxorubicin reistance. Supported by FAPESP. No significant financial relationships to disclose.
Potential budget impact of capecitabine versus 5-FU/LV as adjuvant chemotherapy for stage III (SIII) colon cancer in Canada and its provinces
Authors: K. Virik, C. Skedgel, T. Younis
Journal: Journal of Clinical Oncology (2007)

6581 Background: Adjuvant chemotherapy for SIII colon cancer is an accepted standard of care. Oral Capecitabine (CAP) has been shown to be at least equivalent and possibly superior to 5FU/LV (Mayo regimen) with regards to a superior relapse free survival. This new option is associated with a higher drug cost but improved toxicity profile and appears to be cost-effective (CE). An economic analysis was undertaken to examine the potential budget impact for CAP in Canada and its provinces for 2007 onwards. Methods: A previously developed cost-effectiveness model was adapted to a prevalence perspective to project the net budgetary impact of CAP over a 5 year horizon. The projected population and incidence of colon cancer for each Canadian province from 2007–2016 was obtained and the proportion of patients with SIII colon cancer suitable for adjuvant chemotherapy was estimated from the literature. The average budget impact in the first 5 years (start up phase) and subsequent years (steady state) was assessed in Canadian $. Results: The projected average annual impact for Canada is 13.9 million (M) during the start up phase and $11.8 M during the steady state phase (NL $210K, PEI $63K, NS $424K, NB $282K, QC $2.92M, ON $4.66M, MB $464K, SK $336K, AB $993K and BC 1.45M). Budget impact is greater during the initial start-up phase (2007–11), as the steady state impact (2012–16) includes relapses avoided over a 5-year period. Sensitivity analyses for key parameters will be provided. Conclusions: The annual budget impact of CAP decreases over time and reaches a steady state after 5 years when the full impact of decreased recurrences is captured. As CAP appears to be CE, budget impact analysis has the potential to assist in the planning of healthcare funding resources regarding this treatment option. [Table: see text]
External beam radiation therapy or high intensity-focused ultrasound for localized prostate cancer: A matched pair analysis in the prostate-specific antigen era.
Authors: Gilles Pasticier, Sebastien Crouzet, Pascal Pommier, Christian Carrie, Olivier Rouviere, Jean-Yves Chapelon, Muriel Rabilloud, Laurent Roche, Florence Mege-Lechevallier, Helene Tonoli-Catez, Xavier Martin, Albert Gelet
Journal: Journal of Clinical Oncology (2015)

109 Background: In the absence of randomised study data institutional series have shown High Intensity Focused Ultrasound (HIFU) to produce excellent overall and cancer specific survival rates in patients with localized prostate cancer (LPCa) compared with alternative curative treatments. The aim of this study was to evaluate the oncologic outcome of patients treated with HIFU versus conformal external beam radiation therapy (C-EBRT) without previous or associated androgen deprivation(AD).This study was designed to overcome limitations of case series studies by using a matched pair design in patients treated contemporaneously with HIFU and C- EBRT in two institutions in the same town. Methods: 256 eligible patients with intermediate risk prostate cancer (d’Amico classification) treated between 2000 and 2005 were prospectively followed and matched to a 1:1 basis following know prognostic variables: prostate-specific antigen (PSA) level and Gleason score.190 perfect matches of patients (95 in each group) were further analysed. Progression free survival rate were the primary endpoint. Other endpoints were secondary used of salvage therapy, and survival rate without salvage palliative androgen deprivation therapy (S-ADT).The progression free survival rates were calculated with Kaplan-Meier estimate. For progression free calculation, failure was defined using the Phoenix definition (nadir + 2ng/ml) or at the time of a salvage treatment for local relapse evidenced by control biopsy. Results: The seven years progression free survival rate was not significantly different after HIFU than after C-EBRT (47% versus 52%, p: 0.311) . The palliative androgen deprivation free rate at seven years was significantly different after HIFU than after C-EBRT (85% versus 58%, p: 0.002). Conclusions: The progression free survival rate was not significantly different after HIFU use than after C-EBRT but the rate of patients who need palliative S-ADT was significantly different after HIFU or C-EBRT: Higher rate of S-ADT was associated with C-EBRT use than with HIFU use.
Prospective, multicenter, randomized GITMO-IIL trial comparing intensive (R-HDS) to conventional chemoimmunotherapy (CHOP-R) in high-risk follicular lymphoma (FL) at diagnosis
Authors: M. Ladetto, F. De Marco, F. Benedetti, U. Vitolo, C. Patti, R. Passera, A. Rambaldi, A. M. Gianni, P. Corradini, C. Tarella
Journal: Journal of Clinical Oncology (2007)

8006 Background: The GITMO-IIL trial evaluated if an intensified treatment with ASCT is better than conventional chemotherapy (both supplemented with Rituximab) in high-risk FL at diagnosis. Methods: Eligibility required a FL with aaIPI&gt;1 or IIL&gt;2 score and an age of 18–60. Primary endpoint was EFS. The analysis was intention to treat. Secondary endpoints were PFS, DFS, OS, rate and prognostic value of MR. R-HDS and CHOP-R have been already described (Ladetto et al ASH 2005, Rambaldi et al Blood 2002). Planned sample size was 240 to detect a 20% absolute increase in the 3-years EFS. However the trial was stopped at 136 pts due to R-HDS superiority in EFS at a planned interim analysis. Cross-over was allowed after CHOP-R failure. Centralized PCR-based molecular analysis was planned on BM cells. Results: Age, stage, LDH, bulky disease, B-symptoms ECOG PS, extranodal disease aaIPI, IIL and retrospectively assigned FLIPI were similar in the two arms. CRs were 59% with CHOP-R and 85% with R-HDS (p&lt;0.001). At a median follow-up of 39 months EFS and PFS are 36% and 38% for CHOP-R and 66% and 72% for R-HDS. OS is 83% in each arm. 67% of relapsed R-CHOP pts underwent R- HDS. MRs were 44% after CHOP-R and 80% after R-HDS (p&lt;0.001). MR was associated to a better PFS (p&lt;0.001). Of note, 3yrs PFS of pts with or without MR was similar in the two arms (MR: 67% with CHOP-R and 76% with R-HDS) (no MR: 25% for CHOP-R and 32% for R-HDS). MR was the strongest independent prognostic factor for PFS, EFS and DFS by multivariate analysis. Conclusions: This is the first phase III trial including MR analysis in a high proportion of pts and comparing intensified versus conventional therapy in the rituximab age. This trial indicates that: a) R-HDS has a better EFS and PFS in truly high-risk FL patients; b) MR is the strongest outcome predictor available in FL; c) the similar outcome in pts achieving (or not achieving) MR, regardless of treatment received, indicates that the superior performance of R-HDS is mostly due to its superior MR rate. [Table: see text]
High pretherapeutic Hb- levels tend to decrease SLC: Updated results of a randomized multicentric trial of hf-acc radiotherapy and concurrent chemotherapy in advanced HNC
Authors: R. Semrau, R.-P. Mueller, H. Stuetzer, S. Staar, U. Schroeder, V. Rudat, A. Dietz, P. Volling, M. Schroeder, M. Flentje, H. E. Eckel
Journal: Journal of Clinical Oncology (2005)

5525 Background: Concurrent chemoradiation (RCT) might be first treatment of choice in advanced unresectable HNC. Between 1995 and 1999 a two arm multicentric randomized study with hyperfractionated (HF) and accelerated (ACC) RCT versus HF-ACC-RT was performed. Subgroup analysis tested the influence of pretherapeutic Hb-level to survival and locoregional control. Methods: Untreated stage III/IV oropharyngeal and hypopharyngeal carcinomas were randomized to either HF-ACC-RCT with 5-FU (600mg/m2/d) and carboplatin (70mg/m2/d) on days 1–5 and 29–33 or HF-ACC RT alone. Total RT-dose in both arms was 69.9 Gy in 38 days in ccb-technique (week 1–3: 1,8Gy/d/ week 4–6: bid RT with 1.8/1.5 Gy fractions). A total of 263 pts. have been randomized, 60% of pts. had a pretherapeutical Hb-level >13,5 g/dl. Results: The actuarial analysis presented is based on 240 pts. 113 pts. received RCT and 127 pts. RT. There were 178 oropharyngeal and 62 hypopharyngeal cancers. After a median follow up time of 57 months the survival in local control (SLC) is significantly better in RCT than in RT (p=0,008), with median SLC times of 17 months and 11 months respectively. Also overall survival (OS) shows a benefit for RCT (p=0,016), with a median OS of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. Patients with pretherapeutical hemoglobin levels >13,5 g/dl had higher SLC (p=0,011) and OS rates (p=0,003). RCT improved SLC significantly only in patients with pretherapeutic hemoglobin levels >13,5 g/dl (p=0,009), whereas patients with pretherapeutic hemoglobin levels <13,5 g/dl did not show a significant benefit from RCT (p=0,53). Multivariate analysis of oropharyngeal patients revealed that pretherapeutical Hb levels less 12,7 g/dl and >14,75 g/dl were associated with reduced SLC. Late toxicity in RCT and RT is not significantly different. Conclusions: Concurrent HF-ACC-RCT is superior to HF-ACC-RT alone in oropharyngeal carcinomas. Pretherapeutic hemoglobin level >13,5 g/dl improves SLC and OS and is important for efficacy of concurrent chemotherapy. Hb- levels >14,75 g/dl reduced SLC in multivariate analysis. No significant financial relationships to disclose.
Abstract 14033: Hemodynamic Responses and Histological Effects of Radiofrequency Catheter Ablation to Renal Artery Sympathetic Nerve
Authors: Masaomi Chinushi, Daisuke Izumi, Kenichi Iijima, Katuya Suzuki, Hiroshi Furushima, Yoshifusa Aizawa, Mitsuya Iwafuchi
Journal: Circulation (2012)

Background: Radiofrequency (RF) catheter ablation of the renal artery is therapeutic in patients with drug-refractory essential hypertension, although details of the therapeutic mechanisms have not...