tbuckley/cabot-search huggingface dataset:
Re-irradiation combined with chemotherapy after salvage surgery in head and neck carcinoma: A randomized trial from the GETTEC and GORTEC groups
Authors: F. Janot, D. De Raucourt, M. Castaing, E. Bardet, G. Dolivet, R. Bensadoun, M. Hamoir, P. Marandas, G. Mamelle, J. Bourhis
Journal: Journal of Clinical Oncology (2006)

5508 Background: Full dose re-irradiation combined with chemotherapy has been shown to be feasible after salvage surgery with an “acceptable” toxicity (Cancer 2001; 91:2071–6). We performed a prospective, multicentric, randomized study to assess its carcinologic value. Methods: Between 1999 and 2005, 130 head and neck cancer patients were treated with salvage surgery and then randomly assigned either to full dose re-irradiation combined with chemotherapy (arm A) or absence of post-operative treatment (arm B). Patients eligibility criteria were: recurrence or second primary in a previously irradiated area to at least 45 Gy, absence of distant metastasis, salvage surgery with macroscopic complete resection; possibility of starting adjuvant treatment within 6 weeks after salvage surgery. Patients in arm A received 60 Gy in 12 weeks combined with concomitant 5FU, Hydroxyurea, as previously described (Ann Oncol 1996;7:913–8). Cox model was adjusted with stratification factors: tumor site, center, type of event (recurrence vs second primary). Results: 65 patients were randomized in each arm, including 71% of local and/or regional relapse and 29% of second primary. There was no imbalance in the distribution of age, sex, tumor site, T and N re-staging, and histological gravity signs (N+ with ECE and/or positive margin). The most important acute toxicity related to re-irradiation and chemotherapy was mucositis with ≥ grade 3 in 29% of patients. A moderate and acceptable increase in ≥ grade 3 RTOG late toxicity was observed in arm A (trismus, mucosa, fibrosis). Progression-free survival was significantly improved in Arm A with a hazard ratio of 1.6 (CI 95%, 1.1–2.4, p = 0.01), but overall survival was not statistically different. Conclusions: This is the first randomized trial to evaluate the effect of full dose re-irradiation combined with chemotherapy after salvage surgery. The results showed that re-irradiation and chemotherapy were able to significantly improve progression-free survival, with no significant impact on survival and acceptable toxicity. Supported by ARC. No significant financial relationships to disclose.
Increased late toxicity in 12–20 year survivors of germ cell tumors (GCT)
Authors: D. Raghavan, M. S. Davis, D. Tsao-Wei, R. Ross, S. Groshen
Journal: Journal of Clinical Oncology (2006)

4509 Background: There is extensive literature on occurrence of late effects of cisplatin-based chemotherapy, but it comes from centers of excellence and may reflect case selection or ascertainment biases. Funded by the NIH SEER Program and the Lance Armstrong Foundation, we studied community-based late outcomes via identification of cases from the Los Angeles SEER Tumor Registry and comparison with a control group. Methods: We identified 951 patients treated in Los Angeles County through the records of the L.A. SEER Cancer Registry/Cancer Surveillance Program (CSP) for 1983–1987, giving a minimum follow-up of 12 years. Consent was obtained from physician of record and forms sent to the patients, requesting information about a broad range of demographic, treatment-related and psycho-social issues. In addition, patients were asked to provide a “control”, a friend of approximately the same age at time of diagnosis, known to the patient before diagnosis and known not to have a history of testis cancer. Questionnaires were also sent to controls, to allow data comparison with patients. Anticipated initial difficulties included mobility of young males and invalid addresses. This occurred in &gt; 50% of cases, and we used a planned strategy for acquisition through State agencies, Department of Motor Vehicles, etc. Results: Surveys were returned by 298 cases and 67 control subjects, and 35 patients refused. In 1983–87, success rates were lower, and 142 patients had died. An unexpected problem was reluctance or inability of subjects to identify friends of comparable age to provide a control population. Differences in groups are summarized in the Table. Conclusions: Long term survivors with GCT have an excess of late toxicity, including cardiovascular, neurological, hematologic, musculoskeletal and neoplastic problems, which increase with time. These data should assist in design of surveillance protocols. [Table: see text] No significant financial relationships to disclose.
Prediction of the response of human osteosarcoma xenografts to chemotherapy via gene expression profiling
Authors: J. Ju, Y. Xi, O. Fodstad, S. Bruheim
Journal: Journal of Clinical Oncology (2005)

9521 Background: Despite the increased survival rates of osteosarcoma patients attributed to adjuvant chemotherapy, at least one third of the patients still succumb to their disease. Furthermore, ultra-aggressive combination chemotherapy is associated with considerable acute and long term toxicity. This is of particular concern in patients who may be cured by a simpler and less toxic regimens or do not have micrometastatic disease. Hence, further improvements in the management of osteosarcoma seemingly depend on diagnostic and prognostic tools that may allow for a more risk adapted and individualized treatment. Methods: We have used Codelink human 20K microarrays to obtain gene expression profiles from a panel of ten human osteosarcoma xenografts. As a parameter of antitumor activity, the specific growth delay (SGD) induced by each drug in the individual xenograft lines was assessed. Pearson correlation coefficients between antitumor activity and gene expression have been calculated. Genes were selected for drug efficacy prediction with p<0.01 and where the difference between expression of a gene in the most sensitive and any of the resistant xenografts was at least two fold. Results: For doxorubicin, 94 genes met these criteria, and 86 genes were selected as candidate predictors of the sensitivity to cisplatin. There was an overlap for 31 genes between these two groups. Twenty-nine genes were selected that correlated with ifosfamide antitumor activity, with no overlap. The most abundant types of genes present among the selected genes represented cellular functions that may be linked to drug resistance, i.e. cell cycle regulation, cell growth, signal transduction and transport mechanisms. For example, the ABC-transporter family members ABCB6 and ABCF2 as well as glutathione S-transferees M3 were inversely correlated with the sensitivity to both doxorubicin and cisplatin. The CD44 antigen, which has been linked with resistance to undergo apoptosis, was inversely correlated to ifosfamide antitumor activity. Conclusions: We have identified several sets of response markers that can potentially be used for predicting chemosensitivity of human osteosarcoma patients. No significant financial relationships to disclose.
A humanized antibody against CD40 (SGN-40) is well tolerated and active in non-Hodgkin’s lymphoma (NHL): Results of a phase I study
Authors: A. Forero-Torres, R. R. Furman, J. D. Rosenblatt, A. Younes, K. Harrop, J. G. Drachman, R. Advani
Journal: Journal of Clinical Oncology (2006)

7534 Background: CD40 is a member of the TNF receptor family and is widely expressed on hematologic malignancies of B-cell origin. SGN-40 is a humanized antibody against CD40 with effector cell function and mild agonistic activity. Preclinical toxicity studies and efficacy data supported initiation of a multi-institutional phase I study to test the safety, pharmacokinetics, immunogenicity, and efficacy of SGN-40 in patients with relapsed NHL. Methods: Cohorts of 3–6 pts were treated weekly with a maximum dose of 2, 3, or 4 mg/kg/wk SGN-40. A dose escalation schedule is used such that patients receive 1 mg/kg on D1 and D4, 2 mg/kg on D8, and higher doses on weeks 3–5. Responding patients may receive a second cycle. Further dose escalation up to 8 mg/kg is planned. Results: 16 pts have been treated with multiple histologic subtypes: follicular (1), marginal zone (MZL; 1), mantle cell (4), and diffuse large B-cell (DLBCL; 10). One patient (2 mg/kg) developed a reversible Grade 3 unilateral conjunctivitis and ipsilateral loss of visual acuity. No other dose limiting toxicity has been observed up to 4 mg/kg. Preliminary pharmacokinetic data suggest that the antibody has a relatively short half-life, perhaps reflecting a route of elimination or binding that is not saturated at current doses. Two partial responses have been observed at 3 mg/kg (1 MZL, 1 DLBCL) and one partial response has been observed at 4 mg/kg dose (DLBCL relapsed after autologous stem cell transplant with small volume tumor). Conclusions: Using an intra-patient dose escalation schedule, SGN-40 has been well-tolerated at doses up to 4 mg/kg/wk. Further dose-escalation is ongoing to determine the maximum tolerated dose. Three objective responses have been seen, including two in patients with extensively treated aggressive disease. Correlative studies are underway measuring soluble CD40, cytokine release, effect of FcR polymorphisms, and SGN-40-induced immunogenicity. Given the favorable tolerability and activity, phase II studies in NHL are planned. [Table: see text]
Phase I/II trial of a novel regimen of GM-CSF, IL-2 and pegylated interferon-alpha2b (PEG-Intron) for stage IV melanoma and renal cell carcinoma (RCC)
Authors: M. Odaimi, I. El-Jassous, E. Richa, F. Forte, T. Terjanian, M. Vesoniaraki, J. Lowry, S. Murukutla, M. Dhar, J. Burton
Journal: Journal of Clinical Oncology (2004)

7573 Background: This phase I/II trial was done to assess toxicity and anti-tumor effects of subcutaneous (SC) GM-CSF, IL-2 & PEG-IFN-α2b for stage IV melanoma (MEL) and RCC. Due to reported activity of GM-CSF in MEL, and its biologic effects (esp. on dendritic cells), it was added. Preliminary data in RCC suggests activity and reduced toxicity of pegylated IFNs. Methods: Phase I used a modified Fibonacci design. GM-CSF was escalated first, over 2 dose levels (125 & 250 μg/m2). IL-2 was then escalated from 3 to 5 MU/m2. Initially, the PEG-IFN dose was 1.5 μg/kg; later it was increased to 3.0 μg/kg, due to recent data. GM-CSF was given SC d 1–12. IL-2 was given SC d 3–5, 8–12 & 15–19, and PEG-IFN was given SC on d 17 & 24 q 35 d. A correlative study was done to measure changes in PBM subsets during treatment, and is reported separately. Results: 16 pts (8 MEL; 8 RCC) have been enrolled, with 15 evaluable for toxicity and 14 for tumor response. All planned dose levels were tested, without any dose-limiting toxicity. 6 patients had grade 3 non-hematologic toxicity, with 3 being fatigue; of note was that 2/3 pts had fatigue with non-pegylated IFN (due to a shortage of PEG-Intron). The other grade 3 toxicities were one episode each of reversible hypotension of uncertain cause in cycle 3, hyperglycemia and depression. There was 1 episode of transient grade 3 neutropenia. There was no grade 4 toxicity or treatment-related mortality. Other toxicities were 2 grade 2 injection site reactions and eosinophilia in 1 pt. No ORs were observed, but 1 MEL pt had a skin lesion regress, with biopsy-proven immune cell infiltrates. This pt, and 2 others had SD for >3 mo, while other pts experienced early PD. Conclusions: This 3-cytokine, SC regimen was shown to be safe and well-tolerated. Evidence of biologic activity was seen in 1 patient, and 3 patients had disease stabilization. Changes in immune cell subsets populations were observed (reported separately). A phase II dosing schedule was established and enrollment to complete the 1st stage of phase II is ongoing. Supported in part by Schering-Plough. No significant financial relationships to disclose.
Annals On Being a Doctor Story Slam - Why I Went to Seattle
Authors: Allan S. Detsky
Journal: Annals of Internal Medicine (2016)

Web Exclusives19 January 2016Annals On Being a Doctor Story Slam - Why I Went to SeattleFREEAllan S. Detsky, MD, PhDAllan S. Detsky, MD, PhDFrom the University of Toronto and Mount Sinai Hospital, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/V15-0013 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals On Being a Doctor Story Slam - Why I Went to Seattle This story, "Why I Went to Seattle", by Dr. Allan S. Detsky, is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation. (Duration 6:41)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals On Being a Doctor Story Slam, visit go.annals.org/StorySlam. Author, Article, and Disclosure InformationAuthors: Allan S. Detsky, MD, PhDAffiliations: From the University of Toronto and Mount Sinai Hospital, Toronto, Ontario, Canada.Note: This story is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation.Corresponding Author: Allan S. Detsky, MD, PhD, University of Toronto and Mount Sinai Hospital, 600 University Avenue, Room 429 Toronto, Ontario M5G 1X5, Canada; e-mail, adetsky@mtsinai.on.ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 January 2016Volume 164, Issue 2 Page: SS2 ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Histologic subtypes of ductal intraepithelial neoplasia (DIN) of the breast: Characteristic associations and biology
Authors: J. D. Schwartz, C. Christy, B. Grube, M. Rishi, F. Tavassoli, V. Bossuyt, L. Harris, M. P. DiGiovanna, D. R. Lannin
Journal: Journal of Clinical Oncology (2009)

633 Background: Most invasive breast cancers are associated with more than one histologic subtype of DIN. The clinical and biologic significance of these DIN subtypes is under-appreciated. Methods: We reviewed 853 cases of DIN diagnosed at our University based Breast Center between 2003 and 2008, 568 (67%) of which were associated with an invasive cancer. Cases of pure invasive cancer without DIN were excluded. Results: A single histologic subtype was present in 41% of the cases, two subtypes in 43%, and three in 16%. The most common DIN subtypes present were solid (52%) and cribriform (50%), while the comedo (18%), micropapillary (11%), papillary (9%) and flat (6%) subtypes were less common. Comedo and solid DIN were frequently found together (Odds ratio [OR]) for coexpression 1.94, p&lt; .001) as were micropapillary and papillary subtypes (OR 2.58, p&lt; .005). Comedo DIN was much less likely to be found with papillary (OR .24, p&lt; .005), flat (OR .34, p&lt; .05), cribriform (OR .42, p&lt; .001) or micropapillary (OR .48, p&lt; .05) subtypes. We also examined multiple biological parameters and their association with the different DIN subtypes as shown in the table below. Solid and comedo subtypes tend to be hormone receptor negative, Her2 positive and high grade while the cribriform subtype tends to be hormone receptor positive, Her2 negative and low grade. Papillary and comedo DIN are most likely to be larger lesions. Papillary DIN is least likely to be associated with an invasive cancer. Conclusions: The histologic architecture provides clues to the underlying molecular changes and biological behavior of DIN. This study will begin to help us understand the molecular basis for the different histologic subtypes of DIN, their different clinical behaviors and tendencies to progress to invasive cancer. [Table: see text] No significant financial relationships to disclose.
A randomized trial of weekly high-dose calcitriol and weight-bearing exercise for cancer treatment–induced bone loss (CTIBL) and bone metabolism in ER+ breast cancer (BC) patients.
Authors: L. J. Peppone, R. N. Rosier, K. M. Mustian, M. N. Ling, A. Huston, O. Palesh, J. Q. Purnell, M. C. Janelsins, L. Sprod, G. R. Morrow
Journal: Journal of Clinical Oncology (2010)

9100 Background: CTIBL is a long-term side effect of hormone therapy (HT) and occurs in up to 80% of women being treated for BC. Daily calcitriol (active vitamin D) therapy improves bone metabolism and bone mineral density (BMD), but hypercalcemia is a common side effect. Weight-bearing exercise also enhances bone metabolism and BMD. The aim of this pilot trial is to examine the effect of novel weekly, high-dose calcitriol therapy in combination with weight-bearing exercise on bone metabolism in BC patients. Methods: 40 female ER+, non-metastatic BC patients receiving HT were randomized to 1 of 4 arms for 12 weeks: 1) weekly, high- dose calcitriol (45 μg QW), 2) an individualized weight-bearing exercise program, 3) both, or 4) a daily multivitamin (control). Bone resorption (N- telopeptide of Type I Collagen [NTx]) and bone formation (bone-specific alkaline phosphatase [BSAP]) were measured and changes from baseline to week 12 were calculated. We also created a bone metabolism index [BOMI] (Δ BOMI= Δ Z-score BSAP - Δ Z-score NTx), which comprehensively represents the balance between resorption and formation. Results: Data from the first 16 patients show calcitriol therapy was well-tolerated, with only 8% indicating grade 1 hypercalcemia and no instances of hypercalcemia at grade ≥ 2. A significant increase in bone formation was found for individuals receiving calcitriol + exercise (Δ BSAP= +11.1 μ g/L; p=0.03) and calcitriol (Δ BSAP= +8.6 μ g/L; p=0.04) compared to the control group (Δ BSAP= -4.8 μ g/L). Increases in the bone metabolism index were greater for participants receiving calcitriol + exercise (BOMI=0.98; p=0.24), calcitriol (BOMI=0.58; p=0.49), and exercise (BOMI=0.39; p=0.71) compared to participants in the control group (BOMI=0.16). Conclusions: Calcitriol therapy at 45 μ g QW was well tolerated and interim analyses demonstrate that the combination of calcitriol and weight-bearing exercise may be effective at improving bone metabolism and reducing CTIBL. Clinical trials are warranted to determine the effect of weekly high-dose calcitriol therapy and weight-bearing exercise on BMD in ER+ BC patients. Funding: NCI R25CA10618. No significant financial relationships to disclose.
Suramin: an anticancer drug with a unique mechanism of action.
Authors: C A Stein, R V LaRocca, R Thomas, N McAtee, C E Myers
Journal: Journal of Clinical Oncology (1989)

We administered suramin, an anti-parasitic drug and reverse transcriptase inhibitor, to 15 patients with metastatic cancer. This compound is known to inhibit the binding of growth factors (eg, epidermal growth factor [EGF], platelet-derived growth factor [PDGF], tumor growth factor-beta [TGF-beta]) to their receptors and thus antagonize the ability of these factors to stimulate growth of tumor cells in vitro. There were no complete responses (CRs), four partial responses (PRs) (two of ten adrenal cortex, one of four renal, one of one adult T-cell leukemia-lymphoma [HTLV-1]), and two minimal responses (MRs) (two of ten adrenal cortex). Toxicity included proteinuria (14 patients), reversible liver function test abnormalities (eight), vortex keratopathy (five), adrenal insufficiency (three), coagulopathy secondary to increased circulating levels of glycosaminoglycans (11), and one case of a reversible acute demyelinating polyneuropathy resembling the Guillain-Barrè syndrome. We conclude that suramin is an active agent in the treatment of metastatic cancer, and further work is necessary to define its scope.
Clinical implications of angiogenic factors in patients with hematological malignancies: HGF levels have a prognostic impact especially in patients with AML
Authors: J. G. Kim, S. K. Sohn, D. H. Kim, N. Y. Lee, J. H. Baek, K. B. Lee
Journal: Journal of Clinical Oncology (2004)

6614 Background: Angiogenesis may have a role in the pathophysiology of hematological malignancies and also be a therapeutic target. Increased levels of angiogenic factors have been correlated with poor prognosis in several solid tumors. Accordingly, we evaluated the serum level of variable angiogenic factors and analyzed their prognostic significance in newly diagnosed patients with hematological malignancies. Methods: The ELISA were performed to quantify basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), tumor necrosis factor-α (TNF-α), angiogenin, and matrix metalloproteinase-9 (MMP-9) in stored samples obtained before treatment from patients with AML (30 patients), ALL (10 patients), CML (14 patients) and MDS (9 patients). Results: VEGF, HGF, angiogenin, and MMP-9 levels were significantly higher in patients with CML than in healthy individuals (p<0.0001 for VEGF, HGF and MMP-9, p=0.024 for angiogenin). HGF levels were also higher in patients with AML than healthy individuals (p<0.001). Higher HGF levels correlated significantly with white blood cell count (p=0.014), monocyte counts (p=0.009), and serum levels of LDH (P=0.009) in AML patients. Among 24 AML patients who received remission induction chemotherapy, 17 patients (70.8%) obtained a complete remission (CR). In univariate analysis, HGF levels (p=0.015) and age (p=0.034) were significant parameters predictive for an achievement of CR. In multivariate analysis using logistic regression model, HGF levels was the only parameter strongly predictive for CR (p=0.047). Leukemia free survival (LFS) for AML patients with lower HGF concentrations was superior to that for those with higher HGF concentrations (1-year LFS rates = 75.0% versus 37.5%, P=0.065). Conclusions: The current study demonstrated elevated serum VEGF, angiogenin, and MMP-9 in patients with CML and elevated serum HGF in patients with CML and AML. The HGF concentrations were significantly correlated with an achievement of CR and high HGF levels were associated with worse survival in patients with AML. No significant financial relationships to disclose.