tbuckley/cabot-search huggingface dataset:
The prognostic factors responsible for survival of women with neuroendocrine small-cell cervical carcinoma—A study of 188 women
Authors: D. S. Kapp, J. Cohen, J. Y. Shin, A. Husain, N. N. Teng, J. S. Berek, K. Osann, J. K. Chan
Journal: Journal of Clinical Oncology (2007)

5539 Background: To determine the clinical and pathological factors associated with survival in women with neuroendocrine small-cell cervical carcinoma. Methods: A review of the literature identified 136 patients with neuroendocrine small-cell carcinoma and an additional 52 patients identified from tumor registry databases at four hospitals. Survival analyses and predictors of outcome were analyzed using Kaplan-Meier method and Cox regression analysis. Results: Of 188 patients, the median age was 41.5 years (range: 20–87 years); 135 had stages I-IIA, 45 IIB-IVA, and 8 had stage IVB disease. Of all patients, 55.3% underwent primary surgery, 16.0% had chemoradiation therapy, 12.8% primary radiation therapy, 3.2% chemotherapy alone, and 12.8% had unknown or no primary treatment. Of the women who had initial surgery, 46.8% patients underwent a radical hysterectomy, and 6.4% had a simple hysterectomy. 49.5% of patients with nodal information had lymph node metastases. After initial surgery, 15.4% of all patients had adjuvant radiation therapy, 13.8% chemoradiation, 6.9% chemotherapy, and 2.1% had neoadjuvant chemoradiation. Of the 81 patients who received chemotherapy, 51.9% had etoposide and cisplatin combinations, 25.9% other cisplatin combinations, and 7.4% had cisplatin alone. The 5-year disease-specific survivals for those stage I-IIA, IIB-IVA, and IVB were 36.8%, 9.8%, and 0.0%, respectively (p&lt;0.001). Those with tumors &lt;2 cm showed a trend toward better survival (67.4% vs. 34.4%) compared to those with larger tumors (p=0.057). Women with stage I-IIA disease who underwent a radical hysterectomy had a survival of 42.5% vs. 38.4% without radical surgery. Chemotherapy (adjuvant or radiation sensitizer) was associated with improved survival in patients with stages IIB-IVA disease compared to those who did not receive chemotherapy (17.8% vs. 6.0%; p=0.043). On multivariable analysis, early stage of disease and chemotherapy were independent prognostic factors for improved survival. Conclusions: Advanced stage of disease is a poor prognostic factor for survival in neuroendocrine small-cell cancer of the cervix. Chemotherapy appears to offer a survival advantage, particularly in patients with stage IIB-IVA disease. No significant financial relationships to disclose.
Prognostic relevance of pretreatment soluble vascular endothelial growth factors (A,C,D) and their receptors (R1, R2, and R3) in advanced melanoma patients
Authors: R. Mouawad, C. Soubrane, D. Khayat
Journal: Journal of Clinical Oncology (2007)

8540 Background and aims: Circulating vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) were described as prognostic factors in several cancers. The aim of this study is to evaluate the prognostic values of these parameters in metastatic malignant melanoma diseases. Methods and Patients: Using enzyme-linked immunosorbent assays, VEGFs (A, C, D) and their receptors (1, 2, and 3) were measured in sera of 75 patients with metastatic malignant melanoma in comparison to 30 healthy controls. Disease free survival (DFS) and overall survival (OS) were calculated from the beginning of the treatment until either the progression or the death and analyzed using the Kaplan-Meier method. Results: Pretreatment median sVEGF-A, sVEGF-C as well as VEGFR-3 levels were significantly higher in MMM patients as compared to healthy ones p=0.0017, p=0.005, p&lt;0.00001 respectively). None of the studied markers correlated with gender, age or LDH levels. An inverse correlation between soluble VEGFR-2 and VEGF-D levels was observed (r=−0.33 p=0.040). High soluble VEGF-C and VEGFR-3 were correlated to high tumor burden (p=0.02, p=0.045). However, a relationship with lymph node metastasis was observed with sVEGF-A but not with sVEGFR-3. As shown by univariate analysis, only elevated levels of sVEGF-R1 concentration were found to exert a significantly unfavorable impact on both disease-free (χ 2 =6.64, p= 0.014) and overall survival (χ 2 =8.03, p= 0.0046). Conclusions: Our results suggest that, in metastatic malignant melanoma patients, soluble VEGF-A and VEGF-R3 pretreatment levels may prospectively identify high-risk patients with a worse prognosis; serum VEGFR-1 level may be a predictive factor of time to progression and overall survival. A multivariate analysis (Cox test) is ongoing in order to confirm if this parameter is an independent prognostic factor. No significant financial relationships to disclose.
Pilot program of fast-track germline genetic analyses as part of integrated breast, ovarian, or gastrointestinal personalized cancer care program.
Authors: O. Caron, B. Bressac-de-Paillerets, D. Malka, A. Remenieras, C. Bourgier, C. Uzan, M. Spielmann, M. Blayau, T. Frébourg, S. Delaloge
Journal: Journal of Clinical Oncology (2010)

1546 Background: Current developments of personalized cancer medicine include complex analyses of somatic tumor genetics. Knowledge of germline genetics should also modify the trt strategy in a near future, regarding for example surgical choices (taking into account subsequent cancer risks), as well as medical choices of potential specific dedicated therapeutics (ex., parp-inh). Delay to obtain genetic results is however currently hardly compatible with therapeutic timing. Methods: We set up in a single institution a pilot process to identify candidate subjects for fast genetic testing (i.e., pts with recent cancer diagnosis, history suggestive of genetic predisposition and potential consequences on trt choices) and get their germline genetic results in less than 4 months. Subjects were to be identified during multidisciplinary team (MT) meetings and referred to oncogenetic clinics (appointment arranged in less than 8 working days). The usual rules of genetic testing were applied: discussion of pro/con of genetic predisposition knowledge, use of written informed consent, psychological evaluation. Blood sample was rapidly sent to internal or external genetic labs. When results became available, pts were immediately informed by mail. Results were communicated individually to pts during a visit to geneticist. MT was informed thereafter. Results: From 01/01/2008 to 31/10/2009, 64 pts (59 with breast cancer, 4 with ovarian cancer, 1 with diffuse gastric cancer suspicion) followed the process. Median time from first to second MTM was 114 days (42-140). A germline mutation (GLM) was found in 19/64 subjects (29.7%) (11 BRCA1, 5 BRCA2, 1 CDH1, 2 P53). These positive results modified therapeutic plans in 13 cases (20%): radiotherapy was cancelled in the 2 P53 mutation carriers, 8 non-previously scheduled mastectomies were performed in BRCA carriers (4 ipsi and 4 contralateral), a CDH1 carrier opted for total gastrectomy, 2 pts could be included in targeted clinical trials. 6 pts refused modifications of trt schemes proposed by MTM. Conclusions: Fast genetic counseling management in selected patients is feasible, and is currently becoming a major component of personalized medicine. No significant financial relationships to disclose.
Combination chemotherapy with gencitabine and cisplatin in anthracycline and taxane pretreated metastatic breast cancer
Authors: F. M. Peria, F. E. Zola, D. G. Tiezzi, H. H. Carrara, P. M. Philbert, H. R. Marana, J. M. Andrade
Journal: Journal of Clinical Oncology (2007)

1108 Background: Metastatic breast cancer (MBC) anthracycline (A) and taxane (T) resistant has a complicated management.Combination chemotherapy, even in 2 nd line, may have advantages over single agent therapy. Gencitabine (G) - cisplatin (C) combinations have been used as synergistic salvage therapy in MBC and it’s another option for patients with important symptoms and aggressive visceral disseminated disease. Methods: This trial analyses the safety and efficacy of G-C in A-T pretreated MBC. Eligibility criteria include: confirmatory pathological analyses; measurable disease; adequate performance status, organ and hematological functions. It was not allowed patients with exclusive bone metastasis. They received IV G 750mg/m 2 and C 30mg/m 2 , both d1 and d8 every three weeks for 6 cycles up to a maximum of 9 cycles. Response evaluation was performed every third cycle and in the end of treatment. Results: From February 2005 through December 2006, 31 patients have been evaluated for response and toxicity from G-C combination. For 20/31 patients this treatment was 2 nd line palliative chemotherapy. 26/31 received at least 3 or more cycles (medium 4 cycles) and no one treatment was discontinued due to toxicity. The most frequent site of metastasis was lung (20/31), followed by hepatic in 13 patients, bone in 11, skin in 10, lymph nodes in 7, brain metastasis in 3 and pericardium in only one. Each patient had at least lung or hepatic metastasis and medium of 2 different metastatic sites. According to RECIST criteria, partial response were observed in 8/31, stable disease in 17/31 (55%) and progressive disease in 6 patients. 90% of cycles were given at full dose and at the right time. Hematological toxicity was modest with grade 2–3 (NCI-CTC) leucopenia in 58/140 cycles, grade 1–2 anemia in 40/140, grade 1–2 thrombocytopenia in 27/140 and was none febrile neutropenia. Non hematological toxicity: grade 2 fatigue in 4 patients and grade 2 nausea in 6/31. Following 22 months, global survival was at mean 4.8 months. Conclusions: Combination chemotherapy with gencitabine 750mg/m 2 and cisplatin 30mg/m 2 both d1 and d8 is feasible and effective in A-T pretreated MBC and demonstrated good tolerance with low intensity of collateral effects. No significant financial relationships to disclose.
A genomic strategy to refine prognosis in early stage non-small cell lung carcinoma (NSCLC)
Authors: D. H. Harpole, R. Petersen, S. Mukherjee, A. Bild, H. Dressman, R. Kratzke, M. J. Kelley, J. Garst, J. Crawford, J. R. Nevins, A. Potti
Journal: Journal of Clinical Oncology (2006)

7026 Background. Although stage-specific classification identifies appropriate populations for adjuvant chemotherapy, this is likely an imprecise predictor for the individual patient with early stage NSCLC. Methods. Using previously-described methodologies that employ DNA microarray data, multiple gene expression profiles (‘metagenes’) that predict risk of recurrence in patients with stage I disease were identified. This analysis used an initial ‘test’ cohort of patients with NSCLC (n = 89) that represented an equal mix of squamous cell and adenocarcinoma. Also, each histologic subset had equal number of patients who survived more than 5 years and those who died within 2.5 years of initial diagnosis. The performance of the metagene-based model generated on the training cohort was then evaluated in independent ‘validation’ sets, including two multi-center cooperative group studies (ACOSOG Z0030 and CALGB 9761). Importantly, the CALGB validation was performed in a blinded fashion. Results. Classification tree analyses that sample multiple gene expression profiles were used to develop a model of recurrence, termed the Lung Metagene Model, that accurately assesses prognosis (risk of recurrence and survival), performing significantly (p&lt;0.001, odds ratio: 16.1, multivariate analysis) better than pathologic stage, T-size, nodal status, age, gender, histologic subtype and smoking history. The accuracy of prognosis using the Lung Metagene Model exceeded 90% (leave-one-out cross validation) in the initial training set (n = 89), 72% in the ACOSOG (n = 25), and 81% in the CALGB (n = 84) datasets. The prognostic accuracy was consistent across histologic subtypes and stages of NSCLC. Importantly, this provides an opportunity to re-classify stage IA patients to identify a subset of ‘high risk’ patients that may benefit from adjuvant chemotherapy. Further, stage IB and II patients identified as ‘low risk’ for recurrence, and who present co-morbidities, could potentially be candidates for observation, and those patients predicted to be at ‘high risk’ may benefit from novel therapeutic trials. Conclusions. The Lung Metagene Model provides a mechanism to refine the estimation of an individual patient’s risk for disease recurrence and thus guide the use of adjuvant chemotherapy in NSCLC. No significant financial relationships to disclose.
Use of PCR for BCL2/IgH + cells in stage I/II follicular lymphoma to identify positive cells in bone marrow and peripheral blood that can be cleared by lymph-node irradiation
Authors: A. Pulsoni, I. Della Starza, N. Frattarelli, E. Carlotti, E. Cavalieri, A. Matturro, F. De Angelis, D. Armiento, A. Rambaldi, R. Foa
Journal: Journal of Clinical Oncology (2008)

8571 Background: Stage I/IIA follicular lymphoma (FL) is considered a localized disease that can be adequately treated with radiotherapy alone. Minimal NHL contamination in peripheral blood (PB) or bone marrow (BM) can be detected by qualitative and quantitative PCR. Aim of this study was to evaluate the role of PCR, the impact of radiotherapy and prognosis in localized FL. Methods: BM and PB involvement in FL was investigated by PCR in a series of 25 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy alone. Results: Despite a negative BM biopsy, Bcl-2/IgH+ cells were found at diagnosis in the PB and/or BM of 17 patients (68%). After lymph-node involved field radiotherapy, in 10/16 Bcl-2/IgH positive, valuable patients, a disappearance of Bcl-2/IgH+ cells was observed, which persisted after a median follow-up of 42 months (range 5–79) in all but 2 patients.. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Two patients had a molecular relapse only and were reinduced into a negative PCR status after rituximab treatment. Clinical relapse was observed in 4/25 patients, all of them had Bcl-2/IgH+ cells in the PB and/or BM at diagnosis. After radiotherapy 3 of them persisted bcl2 positive in BM and/or PB and one became negative. Conclusions: In the majority of localized FL, Bcl-2/IgH+ cells could be found in the PB and BM despite a negative BM biopsy. Lymphoma cells can thus reversibly spread from the affected lymph node (s) to PB and BM and durably disappear after lymph node irradiation. Patients with Bcl-2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR. Rituximab can reverse molecular relapses. No significant financial relationships to disclose.
Activating EGFR mutations in patients with non small cell lung cancer: prevalence and predictors in a caucasian series
Authors: Thomas Malfait, Liesbeth Ferdinande, Kurt Tournoy, D Galdermans, Marleen Praet, Veerle Surmont, Ramses Forsyth, Karim Vermaelen, Jan Van Meerbeeck
Journal: Journal of Thoracic Oncology (2012)
Redirection of primary T lymphocytes towards HER2 by T cell receptor gene transfer
Authors: H. Conrad, L. Staerck, K. Gebhard, W. Uckert, H. Bernhard
Journal: Journal of Clinical Oncology (2008)

3061 Background: The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by T cell-based immunotherapeutical strategies. Until now several vaccination studies against HER2 which is overexpressed in about 25% of breast cancer were performed but the objective response rate achieved was only low. The goal of our studies is the adoptive transfer of primary T cells transduced with a HER2-specific T cell receptor (TCR) for patients with HER2-overexpressing breast cancer. Methods: CD8+ T cells isolated from an HLA-A2- donor were stimulated with allogeneic HLA-A2+ dendritic cells (DC) pulsed with the peptide HER2369–377 known to be naturally presented with HLA-A2. HER2369–377 specific T cells were screened via ELISpot and FACS sorting, respectively, cloned and further tested in 51Chromium release assays (51CRA) and ELISA using the corresponding HER3 and HER4 peptides pulsed on as well as HER2-, HER3- and HER4 overexpressing cell lines. Retroviral vectors containing the TCRα or β chain of a HER2-, HER3- and HER4 reactive cytotoxic T cell (CTL) clone were constructed. Following virus production in HEK293 T cells CD8+ T cells were transduced with the retrovirus and tested in IFN-γ ELISA and 51CRA. Results: The CD8+ T cells transduced with the HER2-specific TCR recognized the same panel of HLA-A2-matched, HER2-overexpressing cell lines as the parental CTL clone. As the parental CTL clone, the TCR- transduced T cells were not only able to recognize HER2369–377 but also the corresponding peptides from HER3 and HER4 as determined by lytic activity and cytokine secretion. Conclusions: The fine specificity of a HER2-reactive TCR which also cross-reacts with the corresponding peptides from HER3 and HER4 is conserved following its transduction into CD8+ T cells. This is a promising result for the HER2-directed design of immunotherapies based on TCR-transduced T cells. Cross-recognition especially of HER3 may be beneficial as HER2 and HER3 overexpressing tumors are particularly aggressive. No significant financial relationships to disclose.
Patient-centered prescribing of medications for comorbid illness in older adults with advanced cancer: A qualitative study.
Authors: Jennifer Tjia, Julia Gallagher, Paul Han, Sarah L Cutrona, Kathleen Mazor
Journal: Journal of Clinical Oncology (2014)

122 Background: Polypharmacy is common, burdensome, and potentially harmful in older adults with advanced cancer. According to the IOM, prescribing and coordination of chronic disease medication for these patients is suboptimal. We conducted a qualitative study with patients, caregivers, nurses, and physicians to better understand these issues. Methods: We used semi-structured interviews to explore participants’ views on medication management, care coordination, and communication for advanced cancer patients enrolled in 3 hospice agencies in New England. Eligible hospice patients were aged ≥ 65 yrs, had a diagnosis of cancer, and prescribed ≥5 medications. Family caregivers participated at the patient’s discretion. We also interviewed nurses and physicians to obtain an interdisciplinary perspective on medication coordination and communication. We used content analysis to identify emerging themes. Eighteen (18) patients (mean age 80 yrs [SD 10], 42% female) and 8 caregivers (mean age 63 yrs [SD 16.6], 88% female) were included, along with 10 nurses and 7 physicians from hospice, outpatient oncology and primary care settings. Results: Emerging themes revealed that patients and families were receptive to comprehensive medication reviews upon transition to hospice that assess the ongoing use of longstanding medications for comorbid illness. Effective framing for discussions included a focus on reducing harmful and non-essential medications; a less effective approach emphasized time to benefit (i.e. whether a medication is indicated for active symptom management vs prevention). Hospice nurses reported physician reluctance to discontinue medications, lack of physician confidence in their medication assessments, and lack of prescribing guidelines as barriers to optimizing prescribing. Conclusions: Patients enrolled in hospice for cancer and their families are willing to reassess the ongoing use of chronic medications for comorbid illness; information about medication harms and their impact on quality of life is considered particularly useful. Barriers to optimal prescribing include physician reluctance to discontinue medications and mistrust between providers.
Pulmonary tuberculosis in patients with advanced head and neck cancer.
Authors: W. Su, W. Ko, J. Hsiao, S. Wu
Journal: Journal of Clinical Oncology (2010)

e16030 Background: Patients with head and neck cancer have more chances to suffer from pulmonary tuberculosis. Many patients with advanced head and neck cancer may have long-term survival after anticancer treatment. However, little has been mentioned about the consequence of tuberculosis in these patients. We addressed the impact of pulmonary tuberculosis on clinical outcome of patients with advanced head and neck cancer. Methods: From 2003 to 2007, in a tertiary referred medical center, we retrospectively reviewed the medical records of all 931 patients with active pulmonary tuberculosis, defined as a consistent chest imaging pattern and the growth of Mycobacterium tuberculosis in sputum or respiratory secretions. Totally 18 patients developed pulmonary tuberculosis within 2 years after the initial diagnosis of advanced head and neck cancer (stage III-IV). The demographic data, nutrition status, current cancer status and survival data were collected. Results: Seventeen of 18 patients were males. More than 90% of them have major risk factors (smoking, drinking, and betal-nut chewing) related to head and neck cancer. Eight patients with head and neck cancer were stage IV and all 18 patients received anticancer treatment. Eleven received combined modality therapy, 3 only radical operation, 4 operation alone. All patients received antituberculosis treatment. At the moment of anti-TB treatment, there were 6 patients with cancer-free status. Compared to these 6 patients, patients with uncontrolled cancer had a poor prognosis (survival time: 95% confident interval (CI) in cancer-free patients, 1358-2672 days; 95% CI in uncontrolled cancer: 55-482 days; p=0.0017 by log-rank test). In addition, serum albumin <3.0 g/dl also conferred to a worse prognosis (p=0.043). The cancer-free status and higher albumin levels were independent factors for a longer survival by multivariate analysis. Conclusions: Among patients with advanced head and neck cancer and active pulmonary tuberculosis, the status of uncontrolled cancer signifies a poor prognosis. Besides, poor albumin level in these patients may contribute to poor outcome. No significant financial relationships to disclose.