tbuckley/cabot-search huggingface dataset:
10-year follow up of 120 patients with gastric MALT lymphoma after <i>Helicobacter pylori</i> eradication—Histological residual disease and second cancers
Authors: T. Wündisch, P. Dieckhoff, A. Gunther, M. Stolte, A. Neubauer
Journal: Journal of Clinical Oncology (2008)

8536 Background: Helicobacter pylori (Hp) eradication induces lasting remissions in most patients with localized gastric MALT lymphoma (GML). The long term outcome of a prospective multicenter trial with special respect to second cancers and histological residual disease is presented. Methods: 120 patients with stage I1E disease were followed up for a median time of 122 (range 1-171) months. Histology was the standard for remission evaluation. Histological residual lymphoma (hRD) was diagnosed when normalization of macroscopic findings were persistent but in further follow-up biopsies histologic evidence of lymphoma was present. Prospective data concerning B-cell clonality were collected, the status of t(11;18) was evaluated in 65 patients in retrospect. Results: 80% (96/120) of patients achieved complete histological remission (CR), 80% (77/96) are in continuous complete histological remission (CCR) The estimated mean survival time in the Kaplan Meier analysis is 147 months (95% confidence interval, 138–156). 17% (16/96) of patients showed hRD during follow-up after a median time of 32 (range, 3–68) months, a watch-and-wait strategy was applied and all but one patient entered into a second CR. It is of note, that in 24 patients one or more secondary cancers were documented, 8 lymphomas and 21 solid tumors. Among these were 5 gastric cancers with the lymphoma being in CCR. Conclusions: Cure of Hp infection results in CCR in most patients. Secondary cancers are of concern in these patients. Histological residual disease, B-cell monoclonality, and t(11;18) were present in a considerable number of CR patients. Therefore, a watch-and-wait strategy seems to be justified, when close follow-up is guaranteed. No significant financial relationships to disclose.
Clinical outcome of chemoradiotherapy in elderly patients with non-small cell lung cancer at G.V Montgomery Veterans Affairs Medical Center
Authors: M. Choi, W. Chan, J. Jaiwatana, T. Khansur
Journal: Journal of Clinical Oncology (2007)

19683 Background: More than 2/3 of lung cancer patients are age = 65 and the proportion of elderly patients are expected to rise in the United States. However data on the use of optimal chemoradiotherapy in this group of patients are limited. Methods: All lung cancer patients = 65 years, who received both chemotherapy and radiation therapy at the G. V. Montgomery VAMC between Jan 2000 to Dec 2005, were analyzed from tumor registry and computerized medical records. Patients who only received palliative radiation therapy for bone and brain metastasis were excluded. Results: Among 652 lung cancer patients diagnose, 46 patients = 65 years received both chemotherapy and radiation therapy over the 6 year study period. The median age was 72 (range:65–84) and 70% of the patients were = 70 years. All patients were male with 65% white and 35% black population. The majority of patients were stage III (85%) while there was one stage I and six stage II patients. 41 patients (89%) were able to complete the planned radiation therapy and median dose delivered was 6140 cGy. The chemotherapy regimen was carboplatin and paclitaxel either weekly during radiation therapy and every three weeks in sequential treatment. There was only 1 treatment related mortality and only 15% of patients survived less than 6 months. The 1, 2, 3 year survival rates were 67%, 24%, and 15% respectively and median survival was 15.3 months. 15 patients were treated sequentially(S) with chemotherapy (median cycle-3) followed by radiation therapy and 31 patients concurrently (C) with chemoradiotherapy. (median- 5 weekly treatment) The survival among the two groups did not differ statistically. (median survival-19.1 month (S) vs. 14 month (C) p=0.78) Conclusions: Both sequential and concurrent chemoradiotherapy is feasible and beneficial in elderly patients with lung cancer. Sequential treatments might be as effective as concurrent chemoradiotherapy in elderly VA patient population. No significant financial relationships to disclose.
Tumor specific scFv antibodies for the early detection of non-small cell lung cancer
Authors: T. V. Pedchenko, R. Mernaugh, D. L. Blum, P. P. Massion
Journal: Journal of Clinical Oncology (2008)

22104 Background: The early detection of lung cancer is a critical and challenging need in the management of this deadly disease. Patients with lung cancer are known to produce autoantibodies against tumors antigens early in cancer development. The amino acid sequences present within an antibody's (Ab1) variable region (idiotype) are unique and determine its antigen-binding specificity. Therefore, an antibody (anti-idiotype or Ab2) specific for Ab1 lung cancer autoantibody could be used to detect lung cancer. Methods: Three pooled serum samples with matching gender, age and smoking history were used in biopanning: 20 adenocarcinomas, 20 squamous carcinomas and 20 controls. Alarge (∼2.9 billion) naïve rodent phage-displayed scFv recombinant antibody was cross-absorbed against pooled, purified normal human IgG to remove scFv cross-reactive with IgG present in both normal and lung cancer patients, then panned against pooled, purified lung cancer IgG to select for scFv specific for lung cancer IgG. After two rounds of biopanning, bacterial colonies were picked and induced to express soluble scFv. These scFv were assayed against purified pooled normal and lung cancer IgG. ScFv (Ab2) reactive specifically with pooled lung cancer autoantibodies (Ab1) were then assayed by ELISA against an independent set of individual whole serum samples. Results: We selected and affinity-purified 8 scFvs with significantly higher binding activity to pooled cancer serum IgG as compared to pooled normal serum IgG. We tested 3 of these scFv candidates in a set of individual 31 cases and 13 controls serum presented in the original pools. The binding activity of scFv varied between different tested groups of serum. For example, binding activity of scFv clone selected as a positive for pooled cancer IgGs in biopanning, was above median for 8 out of 16 adenocarcinoma, 10 out of 15 squamous carcinoma, and 4 out of 13 control samples. Two out of these 4 control samples were from patients with previous cancer history. Conclusion: These results demonstrate that scFv specific for lung cancer autoantibodies can be selected from biopanning of scFv library against pooled serum samples but their prevalence in individual samples is extremely variable and will require larger set of candidate to discriminate cases from controls. No significant financial relationships to disclose.
The role of platelets in inflammation at sites of infection : toll like receptor 2/1 mediated platelet adhesion on bacterial peptide-mimetic surfaces
Authors: Kristin Klarström-Engström, C. Skoglund, Hanna Kälvegren, Torbjörn Bengtsson
Journal: Cardiovascular Research (2012)

The role of platelets in inflammation at sites of infection : toll like receptor 2/1 mediated platelet adhesion on bacterial peptide-mimetic surfaces
Use of multiplex mutation genotyping to identify novel and protective mutations in breast cancer
Authors: K. Kalinsky, L. M. Jacks, C. Hedvat, U. Bhanot, S. Patil, A. Heguy, M. Asher, M. Drobnjak, C. Hudis, M. E. Moynahan
Journal: Journal of Clinical Oncology (2009)

11004 Background: We recently analyzed 590 primary invasive breast tumors for PIK3CA mutations by multiplex massARRAY genotyping. We identified a 32.5% PIK3CA mutation rate (manuscript submitted). Associations between PIK3CA mutation status and favorable pathology, such as lower grade tumors, lymph node negativity and hormone receptor (HR) positivity, were observed. Multiplex analysis allows the rapid assessment of mutations not commonly described in breast cancer. To identify activated pathways that may serve as predictive biomarkers, tissue microarrays (TMA) underwent immunohistochemical (IHC) analysis. Methods: 590 archival formalin-fixed paraffin embedded (FFPE) tumors &gt; 1 cm were used to ensure adequate tissue procurement for mutation detection and TMA construction. MassARRAY (Sequenom) genotyping was performed on native DNA to identify PIK3CA, RAS, RET, and other known mutations. IHC staining of the TMAs included assessment of steroid nuclear receptors, HER2 expression, Akt pathway activation (including pAKT, p70S6K, eIF4E), and PTEN. Stained TMAs underwent digital quantitative image analysis and scoring (Aperio, Vista, CA). The Kaplan-Meier method and Cox models were used in univariate and multivariate analysis for associations of mutation status and clinicopathologic features on overall survival (OS) and breast cancer-specific survival (BCSS). Results: Compared to wild-type, PIK3CA mutated tumors (median f/u: 12.8 years) demonstrate a significant improvement in OS (p=0.03) and BCSS (p=0.004). For patients with any PIK3CA mutation, the improvement in BCSS is maintained in HR positive and ER negative subgroups. In addition to PIK3CA mutations, RAS and RET mutations are identified in a small proportion of breast tumors. Additional analysis to evaluate the association of mutation status and biomarker data derived from the TMA analysis will be performed for meeting presentation. Conclusions: We have recently defined the positive prognostic significance of PIK3CA mutations in breast cancer. RAS mutations are confirmed to occur rarely in breast cancer. The finding of RET mutations in breast cancer is novel. Future tumor biomarker identification directed towards predictive measurement will assist in tailoring therapy to appropriate patient populations. No significant financial relationships to disclose.
Renal and intestinal Pi transport adaptation to low phosphorus diet in uremic rats.
Authors: M Loghman-Adham
Journal: Journal of the American Society of Nephrology (1993)

The normal response of the kidney and intestine to a low-phosphorus diet (LPD) is an increased rate of Na(+)-dependent Pi transport by their brush border membranes (BBM). Dietary phosphorus restriction is used to reduce Pi accumulation in chronic renal failure. It is not known, however, if the uremic state alters the adaptive responses to an LPD. The adaptive response of the renal and intestinal BBM vesicles (BBMV) to LPD in acutely uremic (NX) and sham-operated (SH) control rats placed on a normal diet or an LPD was studied. In renal BBMV, the initial Na+ gradient-dependent Pi transport was lower in NX than in SH rats. Na(+)-independent uptake was unchanged. Thyroparathyroidectomy did not reverse the reduced Pi transport in NX rats. Kinetic studies showed a reduction of the apparent Vmax for Pi in BBMV from NX compared with SH rats (738 +/- 69 and 1,078 +/- 90 pmol/5 s.mg for NX and SH rats, respectively; P < 0.05; N = 5) with no change in the apparent Km. In intestinal BBMV, the initial Na+ gradient-dependent Pi transport was not different between SH and NX rats. There was also no difference in Pi transport kinetics between SH and NX rats. The adaptive response to an LPD persisted in renal and intestinal BBMV from NX rats and was comparable to that observed in SH rats: +54% for SH versus +48% for NX rats in kidney BBMV and +70.2% for SH versus +71.8% for NX rats in intestinal BBMV.(ABSTRACT TRUNCATED AT 250 WORDS)
Primary angiosarcoma spleen-rare asymptomatic presentation
Authors: S. Bhaskar, M. Madhubashini, P. Venkat, B. Dhanvanth, K. R. Purushothaman, S. Srinivasan, K. Shilpa, L. Samoya, W. N. O'Connor
Journal: Journal of Clinical Oncology (2008)

21522 Background: Splenic primary angiosarcoma is a rare malignant vasoformative neoplasm with aggressive clinical features and dismal prognosis. Herein we present an unusual asymptomatic presentation with underlying massive splenic tumor, as it is a rare manifestation in clinical practice. Methods: Case studied from the medical unit was followed up with radiological, histo-morphological and immunochemical markers. Results: A 47-year-old male presented with distention of abdomen 2 months. With the exception of mild loss of weight and appetite, no further symptoms or co-morbid conditions were seen. Physical examination revealed massive hepatosplenomegaly and pallor of skin and anemia with hemolytic morphology. Serum chemistry is with in normal limits excepting increase in serum ALP. CT- abdomen with contrast studied showed gross hepatosplenomegaly with multiple discrete nodular lesions in the spleen as well in the liver suggesting mass lesion. Spine showed multiple osteolytic lesions suggestive of metastasis. USG abdomen showed gross hepatosplenomegaly with multiple hypoechoeic nodules and cystic lesions. Splenectomy was performed and the spleen weighed 1,750gms. The histolopathologic picture depicted classical features of primary splenic angiosarcoma, which was confirmed by immunochemical markers CD31, CD34 and vWF. Conclusions: Despite massive splenomegaly with primary tumor, other than hemolytic anemia no complications of malignancy were present. Literature review reveals splenic rupture as a frequent outcome of massive splenomegaly, which was not observed in this. It is an unusual presentation of an advanced primary malignancy with no clinical deterioration. No significant financial relationships to disclose.
Erlotinib versus carboplatin/vinorelbine in elderly patients (age 70 or older) with advanced non-small cell lung carcinoma (NSCLC): A randomized phase II study of the German Thoracic Oncology Working Group.
Authors: M. Reck, J. Von Pawel, J. R. Fischer, C. Kortsik, S. Bohnet, M. von Eiff, W. Koester, M. Thomas, P. Schnabel, K. M. Deppermann
Journal: Journal of Clinical Oncology (2010)

7565 Background: Treatment of elderly patients remains a challenge. We compared the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib which has shown promising results in elderly patients and a modified platinum based regimen with proven efficacy (Deppermann ESMO 2003). Methods: Patients (pts), =/> 70 y, in advanced stage IIIb/IV NSCLC were randomized to erlotinib (E) 150 mg/d p.o. or carboplatin AUC 5 d1 and vinorelbine (CV) (25 mg/m2) d 1,8 every 21 d up to 6 cycles. Further key eligibility criteria: PS 0/1, adequate organ function, measurable disease (RECIST). Primary endpoint was progression-free survival (PFS), secondary endpoints included response rate (RR), overall survival (OS), tolerability, quality of life and correlation with EGFR-marker. Tumor assessments were performed every 42 days. In order to show a non-inferiority in PFS with a 80% power using the Cox Proportional Hazards Model 194 events were needed. Results: Between 06/06 and 08/08 284 pts were randomized to E (144) and CV (140). Median age 76/76 yrs, male 64.6%/70.7%, stage IV 86.1%/86.4%, squamous cell histology 25%/33.6%, never smoker 18%/15% (E/CV). PFS was in favour of CV, median PFS: 2.4 v 4.6 m (HR 1.6, 75% CI 1.22-2.09, p: 0.0005) (E v CV) as well as RR (7.8% v 28.3%, p: 0.0001). No significant difference in OS appeared (MST E: 7.3 m v CV: 8.4 m, HR: 1.24, 75% CI 0.9-1.71). In Never Smokers PFS (median PFS: 3.7 v 4.3 m, E v CV, HR 0.72, 75% CI 0.35-1.48) and OS (MST: 16.5 v 17 m, E v CV, HR 0.99, 75% CI 0.38-2.57) were comparable. More skin toxicity and diarrhea was observed by E compared to more myelotoxicity, neurotoxicity and obstipation with CV. Less severe adverse events were observed with E (81 v 102, E v CV). Conclusions: CV had an increased efficacy compared with E in the overall population whereas subgroups showed comparable results. Analysis of molecular EGFR-marker is ongoing and will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Roche AstraZeneca, Lilly, Merck, Roche
Complete pathologic response in the primary of rectal or colon cancer treated with FOLFOX without radiation.
Authors: A. Cercek, M. R. Weiser, K. A. Goodman, D. L. Reidy, W. D. Wong, J. G. Guillem, L. K. Temple, D. Schrag, P. Paty, L. Saltz
Journal: Journal of Clinical Oncology (2010)

3649 Background: Stage II/III rectal cancer is treated with chemotherapy (chemo) plus radiation therapy (RT) followed by surgery, and then post-op chemo. Pelvic RT reduces local recurrence, but most studies do not show a survival benefit. We retrospectively reviewed patients who received pre-op FOLFOX without RT as initial management of locally advanced rectal cancer, either because they had suspected metastatic disease, or relative contraindications to RT, or refused RT. We also reviewed preoperative FOLFOX-based chemo in patients with known synchronous metastatic disease who underwent resection of the primary. Methods: Six pts with stage II/III rectal ca (Table) who received pre-op FOLFOX without RT, and 14 pts with synchronous metastatic colon or rectal cancer treated with pre-op FOLFOX ± bevacizumab (bev) followed by resection of the primary were identified. Path reports were reviewed to assess the pathological complete (path CR) and near-complete (>90% treatment effect) response rates. Electronic records were reviewed for local and distant recurrence. Results: Of the 20 colorectal cancer pts treated with FOLFOX or FOLFOX-bev without RT, 7 (35%) achieved a pCR. Of the 6 patients who received pre-op FOLFOX for localized rectal cancer, 2 had pCR and three had 99%, 95%, 90% treatment effect. These 5 remain free of disease at time of last f/u. The sixth pt had minimal treatment effect in the primary:he failed in the liver and lung one year post resection without local failure. Of the 14 pts with metastatic colon or rectal ca, 4 received FOLFOX and 10 received FOLFOX-bev. Of these, 5 had pCR in the primary (4 with FOLFOX-bev, 1 with FOLFOX). Conclusions: Even considering possible recall bias, the path CR rate to FOLFOX seen in these primaries appears much higher than seen in metastases (path CR rate less than 0.5% in metastatic disease). This warrants further study, and supports our prospective trial of pre-op FOLFOX-bev, without RT, in selected patients with locally advanced rectal cancer. Patients with stage II/III rectal cancer treated with FOLFOX Patient ERUS stage at diagnosis Pathologic stage Treatment effect (%) 85 F T3 N1 T0N0 (pCR) 100% 48 M T3 N1 T0N0 (pCR) 100% 45 F T3 N1 T1NO 99% 59 M T2 N1 T2N1 95% 36 F T3 N1 T2N0 90% 53 M T3 N1 T3N1 10% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Alchemia, Biothera, Delcath, ImClone Systems, Merck, Novartis, Roche Pfizer Amgen, Biothera, Bristol-Myers Squibb, Curetech, Genentech, ImClone Systems, Lilly, Merck, Pfizer, Roche, Tercica
Chemotherapy for breast cancer given during pregnancy: A case serie
Authors: A. E. Ring, P. A. Ellis, A. Jones, C. Shannon, E. Galani, I. E. Smith
Journal: Journal of Clinical Oncology (2004)

715 Background: Experience with chemotherapy for breast cancer during pregnancy is limited. This retrospective case series presents the accumulated experience of four London hospitals in giving chemotherapy to 28 pregnant patients with breast cancer. This represents one of the largest series of such patients to date. Methods: A retrospective case note review was performed at four London hospitals to identify women who received chemotherapy for breast cancer whilst pregnant. Results: Twenty-eight women were identified who had received chemotherapy for breast cancer whilst pregnant, with stage I (2), stage II (11), stage III (11) and stage IV disease (4). The mean maternal age at diagnosis was 34 years (range 28–42), the mean gestational age at diagnosis was 17 weeks (range 4–33). Seventeen patients underwent surgery whilst pregnant, at a mean gestational age of 16 weeks (range 5–29). Chemotherapy was given in the adjuvant (17), neoadjuvant (7) and palliative settings (4). Sixteen patients received anthracycline-based chemotherapy, and 12 CMF. One patient was treated in the first trimester, but had a spontaneous abortion. The remaining 27 patients were treated in the second and third trimesters, commencing at a mean gestational age of 22.7 weeks (range 15–33). A total of 116 cycles of chemotherapy were given, with a median of 4 cycles during pregnancy (range 1–6). Chemotherapy was well tolerated at full doses without major complications. The mean gestational age at delivery was 37 weeks (range 30–40). No congenital malformations were reported, and the mean birth weight of the infants was 2.9kg (range 1.4 to 3.5). Two of the newborns experienced respiratory distress and a total of 5 required transfer to a specialised neonatal unit, but all made full recoveries. Conclusions: In terms of peri-partum complications and immediate fetal outcome, chemotherapy can be safely administered to women with breast cancer in the second and third trimesters of pregnancy. No significant financial relationships to disclose.
Dose-Response Studies on the Ability of 7,12-Dimethylbenz[ a ]anthracene and Benz[ a ]anthracene to Initiate Skin Tumors 2
Authors: T. J. Slaga, G. T. Bowden, J. D. Scribner, R. K. Boutwell
Journal: JNCI Journal of the National Cancer Institute (1974)

Dose-response curves depicting the turnerinitiating abilities of the powerful carcinogen 7,12-dimethylbenz[ a]anthracene (DMBA) and the supposedly weak carcinogen or noncarcinogen benz[a]anthracene (BA), applied to Charles River CD-I female mice, revealed that: A single topical dose of either 0.5, 5, 10, 20, 100, or 200 nmoles DMBA, followed 1 week later by twice weekly applications of 0.25% croton oil, induced 0.4, 2.3, 6.0, 5.5, 6.2, and 16 papillomas per mouse, respectively, at 24 weeks. One topical application of 5, 40, or 200 nmoles DMBA, followed by twice weekly applications of 17 nmoles 12-O-tetradecanoylphorbol-13-acetate (TPA), produced 3.8, 15, and 26 papillomas per mouse at 20 weeks after promotion. When DMBA was injected intra peritoneally in amounts of 0.6, 1.2, 2.4, or 4.8 μmoles and followed by twice weekly TPA promotion, the mice developed 7.8, 11.8, 11.6, and 4.4 papillomas per mouse at 20 weeks. BA initiated papillomas in 50% of mice by 15 weeks after a single dose of 2.2 μmoles BA followed by twice weekly applications of 16 nmoles TPA. A single topical application of 1.1, 2.2, 4.4, or 8.8 μmoles BA, followed by promotion, induced 0.9, 1.6, 2.6, and 2.9 papillomas per mouse by 24 weeks. Results suggested that every complete carcinogenhas both initiating and promoting abilities, whereas certain weakly carcinogenic or noncarcinogenic polycyclic hydrocarbons may have either initiating or promoting activities.