tbuckley/cabot-search huggingface dataset:
Adenocarcinoma of stomach-epidemiology and treatment results of rural South Indian experience
Authors: R. Madiajagane
Journal: Journal of Clinical Oncology (2004)

4172 Background: Adenocarcinoma of stomach is one of the common problems in India. Most often this is diagnosed in locoregionally advanced or in Metastatic stage.Chemotherapy is needed in most cases of ca Stomach .This study deals with adenocarcinoma of stomach in the rural south Indian population.This is a retrospective analysis. Methods: The diagnosis was by endoscopic biopsy. Non Metastatic ca stomach was treated with initial surgery.Chemotherapy was offered to those with Metastatic,node positive or seosa or muscle positive patients The common chemotherapy protocol used was ELF (Etoposide 100 mg/m2,Leucovorin 30mg/m2,5FU 350 mg/m2 all IVF d1-d3) at three weekly interval for six cycles. Results: Total of eighty patients were analysed.The lesion was in70% distal, 17% proximal and 13% unknown site. In 60% the infiltration was upto serosa or beyond and in 7% upto muscle.20% had liver involvement. Nodes were involved in 44% and peritoneum was involved in 15%. 29 patients had adjuvant and 51 had palliative chemotherapy. All patients who had adjuvant chemo had surgery(partial gastrectomy in 69%,total gastrectomy in 24% and gastro esophagectomy in 7%).37% of patients on palliative chemo had surgery like partial gastrectomy, jejunostomy or gastrojejunostomy. 59%in adjuvant and 29%in palliation were regular for treatment.31% relapsed in adjuvant group.In the palliative group56%had stable disease and 44%had progressive disease.The follow up in adjuvant group was 1–155Wks(mean 36 and median 28)and in the palliative group 1 – 52 wks(mean 11 and median 5 wks).Toxicity is grade 1 or 2 and there was no toxic death. Conclusion: Chemotherapy is needed for most of these patients of ca stomach. ELF protocol was simple and relatively non toxic protocol.Inspite of this a fair proportion in both adjuvant and palliative groups were not regular on treatment. The main reason is unabated symptoms of malignancy (in palliation group) and nutritional complications of gastrectomy (in the adjuvant group). Apart from addressing superior chemotherapy, we also need to investigate areas to improve patient compliance, nutritional complications of gastrectomy and quality symptom management like standard gastric diversion procedure. No significant financial relationships to disclose.
Laparoscopic-assisted mesorectal excision (LAME) after neoadjuvant chemoradiotherapy (CRT)
Authors: J. Maurel
Journal: Journal of Clinical Oncology (2005)

3625 Background: Preoperative radiotherapy followed by mesorectal excision (MSE) reduces local recurrences compared to MSE (Kapiteijn et al, NEJM, 2001). Laparoscopic assisted colectomy is at least as effective as open surgery in colon carcinoma (Lacy et al. Lancet, 2002). The aim of this study was to evaluate the safety and efficacy of LAME after CRT. A secondary objective was to evaluate the outcome, in patients with complete pathological response without adjuvant treatment; Methods: Eligible criteria included adenocarcinoma of the rectum; uT2N1or uT3–4Nx stage by endoscopic ultrasonography (EUS) and non-metastatic disease by chest X-ray and helical abdominal scan. CRT consisted on 5FU (225 mg/m2 administered over 24 hours per 5 days) concomitant with pelvic irradiation (2.0 Gy per day, 23 fractions total). LAME was planned 5–7 weeks after CTR. Only patients with residual tumor after CRT received adjuvant chemotherapy with 5FU 3 g/m2 in 48 h CI and folinic acid (200 mg/m2) every 15 days per 6 cycles; Results: From Oct 2000 to March 2003, 55 patients were included. Median age was 63 (range 42 to 83), EUS staging: T2N1 2%;T3N0 54%;T3N1 34%;T4N0 6%;T4N1 2%and non evaluable 2%. All patients completed CRT and underwent surgical resection (R0 94%, R1 4%, R2 2%). There was not grade 3/4 hematological toxicity; Non-hematological toxicity was mild; diarrhea grade 3 in 2%, mucositis grade 3 in 2%. Conversion rate to open surgery was 29%. Median excised nodes were 10 (range 1–33). Complete pathological response (pCR) was observed in 22% of patients. Mean hospital stay was 7.4 days (range 4 to 43). With a median follow-up of 34 months, disease free survival (DFS) and overall survival was 84% and 89% respectively. A significant prolongation on DFS (p=0.00001) was observed in patients with pT0N0 (100%) vs pT1–4N0 (91%) vs pTxN1 (40%). Conclusions: LAME after CRT is feasible and survival is comparable to best series with open MSE. A surveillance strategy in patients with pCR after CRT and LAME, seems reasonable. No significant financial relationships to disclose.
Treatment (Tx) guidelines for skin and mucosal events in patients with solid tumors (pts) receiving TH‐302, a tumor selective, hypoxia‐activated prodrug.
Authors: M. J. Borad, N. Boyer, J. G. Curd, U. K. Sunkara, K. Awerkamp, M. E. Lacouture
Journal: Journal of Clinical Oncology (2011)

e13616 Background: TH‐302 is essentially inactive in normoxic conditions and is activated in regions of severe hypoxia (<1% O2 saturation), releasing a bromo‐isophosphoramide mustard that alkylates DNA. The epidermis and superficial mucosa contain areas of severe hypoxia; TH‐302 can produce events in these regions that likely represent the local activation of TH‐302. Methods: Tx guidelines to prevent and manage TH‐302‐induced events were empirically developed with research personnel during three phase I/II clinical trials (Table). Results: Dermatologic events associated with TH‐302 in the three trials (n = 355) included rash (41%), stomatitis/mucosal inflammation (33%), hyperpigmentation (14%), hand foot syndrome (7%), and cheilitis (3%). Of these, 7% were grade 3; none were grade 4 or 5. The skin/mucosal events were dose‐proportional, predictable, and reversible. Implementation of tx guidelines decreased the frequency and severity of these events. Conclusions: The tx guidelines allow TH‐302 administration at clinically active doses and should be prospectively investigated in future comparative studies. Toxicity Prophylaxis Grade 1 Grade 2 Grade 3 Intertriginous rash Desitin or zinc oxide cream (40%) BID to perineal area; cool packs to inguinal region during TH‐302 infusion; gentle skin care Preparation‐H to perineal area before infusion + continue prophylaxis + Silvadene 1% cream BID Silvadene 1% cream + triamcinolone 0.1% cream BID Continue grade 2 tx regimen + interrupt TH‐302 until grade 0‐1 Mucositis Oral cryotherapy during TH‐302 infusion Continue prophylaxis + anti‐inflammatory or antibacterial mouthwashes Interrupt TH‐302 until grade 0‐1 + manage oral pain with elixir (hydrocortisone 200 mg, nystatin 2 million units, tetracycline 1500 mg, and Benadryl equal to 250 cc) swish and swallow 1 teaspoon TID and pain control Continue grade 2 tx regimen + reassess pt after 2 weeks Hand‐foot syndrome Ammonium lactate 12% cream or heavy moisturizer BID Continue prophylaxis + cryotherapy to hands/feet Continue prophylaxis + clobetasol 0.05% cream QD Interrupt TH‐302 until grade 0‐1; discontinue prophylaxis; increase clobetasol 0.05% to BID + pain control
Active Her-2/neu signal transduction in breast cancer –relevance of a ligand-independent activation mechanism and impact on the efficacy of trastuzumab-based treatment
Authors: G. Hudelist, W. Koestler, J. Attems, K. Czerwenka, R. Mueller, M. Manavi, G. Steger, E. Kubista, C. J. Zielinski, C. F. Singer
Journal: Journal of Clinical Oncology (2004)

649 Background: Proteolytic shedding of the Her-2/neu extracellular domain (ECD) has been demonstrated to initiate receptor phosphorylation and thereby Her-2/neu activation in vitro. The aim of the present work was to investigate the clinical relevance of ECD cleavage for Her-2/neu activation and the clinical relevance of active intracellular Her-2/neu signalling reflected by tyrosine kinase phosphorylation in patients treated with trastuzumab-based therapy. Methods: Sera from 62 patients receiving trastuzumab-based treatment for Her-2/neu over-expressing metastatic breast cancer were analyzed for pre-treatment ECD levels by enzyme-linked immunosorbent assay (ELISA). The degree of Her-2/neu phosphorylation/activation of tumor specimens was assessed by immunohistochemistry using a Her-2/neu phosphorylation state specific antibody (PN2A). The Her-2/neu phosphorylation status was then correlated with the patients' ECD levels and clinical course of disease. Results: Serum ECD levels were significantly higher in 15 (24%) patients with tumours exhibiting activated Her-2/neu as compared to those without detectable Her-2/neu phosphorylation (median 148.2 ng/ml vs. 28.5 ng/ml, p=0.01). Whereas response rate only tended to be higher in patients with Her-2/neu-phosphorylated breast cancer (47% vs. 34%, p=0.197), both uni- an multivariate analyses revealed that the median progression-free survival under trastuzumab-based treatment was significantly longer in patients with Her-2/neu-phosphorylated breast cancer 11.7 (95% CI 5.2 to 18.3) as compared to the progression-free survival of 4.5 (95% CI 3.4 to 5.6, p=0.001) months observed in patients with tumours without phosphorylated Her-2/neu. Conclusions: These data strongly suggest that proteolytic cleavage of the ECD represents a biologically relevant ligand-independent mechanism of Her-2/neu activation in vivo. The influence of Her-2/neu activation status upon the efficacy of trastuzumab merits further investigation in larger prospective trials. No significant financial relationships to disclose.
Histopathologic and immunohistochemical findings of skin rash to HER1 and HER1/2 inhibitors during anticancer therapy.
Authors: B. Nardone, V. G. Kaklamani, K. M. Nicholson, M. Newman, J. Guitart, P. Gerami, N. Talarico, A. Rademaker, D. P. West, M. E. Lacouture
Journal: Journal of Clinical Oncology (2010)

2581 Background: Inhibitors of human epidermal receptors (HER) have shown benefit against a wide range of solid tumors. However, their use is associated with a rash in up to 90% of patients, which impacts quality of life and may lead to therapeutic dose modification or interruption. The histologic characteristics of affected skin are not clearly understood, precluding the development of rational therapies. The aim of this study is to evaluate differences in histologic and immunohistochemical (IHC) alterations in skin rash due to lapatinib, a dual HER1/2 inhibitor (iHER1/2) and the single HER1 inhibitors (iHER1) cetuximab, erlotinib, and panitumumab. Methods: Skin biopsies were collected from 8 patients with skin rash for each iHER (n=32). Two dermatopathologists performed blinded independent analysis of epidermis, dermis, follicle, and inflammatory infiltrates. In addition, specimens were stained for 17 receptor/pathway biomarkers. Blinded IHC analysis was conducted to determine percentage and intensity of expression for each biomarker and compared between four iHER. Results: A significant increase in the expression of pAKT in the epidermis and dermis when comparing iHER1/2 lapatinib, to iHER1 cetuximab, erlotinib, and panitumumab; a significant decrease in the expression of K16 and p27 in dermis; and a significantly higher expression of ERK1 in the dermis compared to erlotinib. Moreover, decreased epidermal atrophy and follicular neutrophilic infiltrate were observed in skin of patients on iHER1/2 when compared to the 3 iHER1. Conclusions: Our findings suggest a lower inhibition of epidermal kinetics and decreased follicular inflammation in iHER1/2-induced rash. These findings underscore differences in skin toxicity with specificity of HER blockade and are concordant with clinical data suggesting lower severity of skin toxicity with the iHER1/2 lapatinib, compared to iHER1 cetuximab, erlotinib, and panitumumab. Less severe skin rash may improve quality of life and ensure consistent dosing with iHER therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Residual Lymphocytes in GM-CSF and IL-15 Differentiated Monocyte-Derived Dendritic Cells Enables Cytotoxic T Lymphocyte Responses.
Authors: Melinda Y. Hardy, Andrew J. Kassianos, Ray Wilkinson, Annelie Vulink, Derek N.J. Hart, Kristen J. Radford
Journal: Blood (2007)
Use of the novel biomarker (HOXB2) to predict response to pancreatectomy for pancreatic cancer
Authors: A. V. Biankin, J. G. Kench, D. Segara, D. A. Skalicky, S. A. Biankin, P. H. Cosman, N. D. Merrett, E. A. Musgrove, S. M. Henshall, R. L. Sutherland
Journal: Journal of Clinical Oncology (2007)

10526 Background: Pancreatectomy is the only therapeutic intervention that offers the chance of long term survival for patients with pancreatic cancer, however, only 10% of patients who undergo pancreatectomy survive &gt; 3 years with prognostic factors only determined after pathological examination of the resected specimen. Identification of a biomarker of response to surgical resection that can be determined preoperatively offers the potential to significantly improve survival and quality of life for patients with PC by improving patient selection for pancreatectomy. Methods: We examined the aberrant expression of over 20 genes identified using transcript profiling or known to be important in carcinogenesis using immunohistochemistry and in-situ hybridisation in a cohort of 124 patients with pancreatic cancer to identify potential biomarkers of prognosis and response to operative resection. Results: Aberrant expression of p53, p21WAF1/CIP1, p27KIP1, p16INK4A, cyclin D1, cyclin E, DPC4/Smad4, EGFR, beta-catenin, sfrp4, LMO4, HOXB2, S100P, S100A6, S100A2, RAI3 and CRBP1 were identified in a significant proportion of PC. Multivariate analysis of clinicopathological variables (tumor size, differentiation, subtype, lymph node metastases, perineural invasion and vascular space invasion), treatment parameters (margin involvement, adjuvant therapy, resection type), and aberrant expression of the above candidate biomarkers identified that HOXB2 expression and resection margin involvement by tumor were the only 2 independent prognostic factors. Patients who had absent HOXB2 expression and had clear margins after pancreaticoduodenectomy (48%) had an actual survival of 40% at 3 years and 21% at 5 years, compared to those with HOXB2 expression and/or positive surgical margins who had all died by 28 months. Conclusion: HOXB2 expression may represent a surrogate marker of advanced disease, can potentially be assessed preoperatively using FNAB, and is currently the best predictor of outcome and response to operative resection to be reported. Preoperative assessment of HOXB2 expression has potential clinical utility in predicting response to operative resection for PC to allow better selection of patients for operative intervention. No significant financial relationships to disclose.
Dysfunctional breathing in asthma patients
Authors: Svetlana Chikina, Natalya Daragan, Alexander Chuchalin
Journal: European Respiratory Journal (2011)

Dysfunctional breathing (DB) coexisting with BA presents difficulties for clinicians. Criteria to distinguish these conditions are not defined. This study was aimed at investigating DB in patients with or without BA.   Methods:  This was a single-center cross-sectional study. We used the language of dyspnoea, HADS scale, the Nijmegen questionnaire, spirometry, capnometry, and blood gas analysis.   Results:  29 BA patients and 7 DB patients participated in the study. Of BA patients, 5 had clinical signs of DB (BA+DB group). Patients with DB and BA+DB described their dyspnoea as “ I am gasping for breath ” (28.6% and 40%, respectively, vs 4.2% of “pure” BA) and “ My breathing requires more concentration ” (42.9% and 42.9% vs 10.3%, respectively). Only 1 BA patient (4%) described expiratory difficulties.  FEV 1  was 2.35±0.95  L  in “pure BA”; 2.08±0.62  L  in BA+DB and 3.13±0.9  L  in DB group (p  Anxiety, hyperventilation and blood hypocapnia prevailed in BA+DB group; median HADS-A scores were 12.0 (11.0 – 13.0), 9.0 (4.0 – 11.0) and 7.0 (3.0 – 8.0), the Nijmegen scores were 30.0 (27.0 – 31.0); 21.0 (15.0 – 32.0) and 14.5 (8.0 – 25.5) in BA+DB, DB and “pure” BA groups, respectively.   Conclusion:  Most BA patients perceive inspiratory dyspnoea but its quality depends on coexisting DB. Alveolar and arterial CO 2  are not indicative in up to 75% of patients with DB. Therefore, distinguishing DB from BA should be primarily based on verbal descriptions of dyspnoea.
Elevated ras oncogene expression correlates with lymph node metastases in breast cancer patients.
Authors: J Lundy, R Grimson, Y Mishriki, S Chao, S Oravez, F Fromowitz, M V Viola
Journal: Journal of Clinical Oncology (1986)

The protein product of the ras cellular oncogene(s) (p21) was assayed in primary breast carcinomas from two groups of patients who had different axillary lymph node status. Using an immunohistochemical assay, the intensity and percent of neoplastic cells demonstrating ras p21 antigen staining were significantly higher in the primary tumors from patients with lymph nodes positive (LN+) for malignancy (20 patients) compared with the lymph node negative (LNO) group (21 patients). The expression of p21 also correlated with tumor size. Age and estrogen receptor status did not influence p21 staining. The antigen expression of p21 was similar in intensity and distribution in the primary tumor and regional lymph node metastases. Enhanced expression of p21 in primary breast cancers that metastasize to regional nodes indicates that ras p21 may be a determinant of the malignant potential of breast cancer cells and may represent a new class of more biologically relevant tumor markers.
Thromboembolic events and bleeding in patients with metastatic carcinoma treated with chemotherapy and bevacizumab.
Authors: Ana Isabel Ferrer, Jose Luis Sanchez, Maria Carmen Rodriguez, Carmen Soriano, Luis Alberto Aliaga, Sandra Garcia Nieto, Maria Carmen Alonso, Antonio Fernandez
Journal: Journal of Clinical Oncology (2012)

e19576 Background: An increased risk of thromboembolic events (TE) and bleeding (Bl) has been observed in some trials among cancer patients (CP) treated with bevacizumab (B) and chemotherapy (QT). Our aim is to assess specific risk of TE and Bl in unselected CP treated with QT and B in general clinical practice. Methods: Retrospectively, we collected data of all metastatic CP treated with QT and B in our 3rd level hospital, since April 2007 to December 2011. Clinical histories were review to collect any TE or bleeding occurred during or immediately after the treatment. We compare risk of TE/bleeding with 94 control CP treated with QT during the same period. Results: A total of 143 CP were treated with B and QT. Of them, 105 patients (73,4%) due to metastatic colorectal cancer, 19 patients (13,3%) due to metastatic breast cancer and 12 patients (8,4%) due to metastatic non-small cell lung cancer. Median duration of B treatment was 175 days (range 18-1079). During the treatment, 9 patients (6,3%)had a venous TE, 1 patient (0,7%) had and artherial TE, and 5 patients (3,5%) had severe bleeding. Among the 94 control patients, 8 had a venous TE (8,5%), 2 had an artherial TE (2,1%) and 1 had a severe bleeding (1,1%) Risk of TE was not statistically different between groups, (OR 1.58, IC 95% 0.63-3.96) Neither for venous TE (OR 1.38, IC95% 0.51-3.72) nor for artherial events (OR 3.08, IC95% 0.27-34.5) No differences in bleeding risk was found (OR 0,29, IC 95% 0.03-2.58). Conclusions: B added to QT treatment does not appear to increase risk of TE or bleeding in general metastasic population. Although a larger number of patients would evaluate better this risk, we could assess that if patients are selected by other clinical risk factors, bevacizumab does not confer an increased risk of TE or haemorrhage.
Irinotecan plus carboplatin versus etoposide plus carboplatin in extensive disease small cell lung cancer: A randomized phase II trial
Authors: A. Schmittel, L. Fischer von Weikersthal, M. Sebastian, H. Link, K. Schulze, E. Thiel, U. Keilholz
Journal: Journal of Clinical Oncology (2005)

7046 Background: Superiority of irinotecan/cisplatin combination over etoposide/cisplatin has recently been suggested in a small phase III study in patients with small cell lung cancer (SCLC). This trial compared the efficacy of irinotecan/carboplatin (PI) versus the frequently preferred standard regimen etoposide/carboplatin (PE) in SCLC. Methods: Chemotherapy-naïve extensive disease SCLC patients were randomly assigned to receive carboplatin AUC 5 mg x min/mL either in comination with 50 mg/m2 of irinotecan on days 1, 8 and 15 (Arm A) or with etoposide 140mg/m2 days 1–3 (Arm B). In arm A treatment was repeated every 4 weeks, in arm B every 3 weeks. Response assessment was performed after cycles 2, 4 and 6 and every 3 months thereafter. Toxicity was assessed once weekly.Results: 74 patients were randomized. Today 59 patients are already evaluable for response assessment. CR/PR/SD/PD was observed in 10%/61%/6%/23% with PI and 0%/50%/11%/43% with PE. Significant differences in grade 3 and 4 toxicity was observed for thrombopenia (18% PI vs 50% PE) and neutropenia (27% PI vs 62% PE). There were no significant differences in febrile neutropenia. Grade 3 and 4 diarrhea was manageable and as expected significantly more frequent with PI (12%) than with PE (6%). Median PFS was superior with 9 months (95% CI 6.8 - 11.2) with PI and 6 months (95% CI 4.2 - 7.8) with PE (p=0.02). Conclusions: Irinotecan plus carboplatin improves response rate and PFS over standard PE. Hematotoxicity is favourable. Per protocol this trial is currently extended into a randomized phase III trial to assess impact on overall survival. No significant financial relationships to disclose.