tbuckley/cabot-search huggingface dataset:
A phase II trial of gemcitabine and irinotecan in patients with refractory or relapsed non-small cell lung cancer
Authors: F. Ohyanagi, M. Nishio, T. Horai, K. Kasahara, K. Shibata, Y. Takeda
Journal: Journal of Clinical Oncology (2004)

7325 Background: Non-platinum regimen may improve efficacy with less toxicity than platinum-based combination. Synergistic effects between gemcitabine and irinotecan have been reported in preclinical studies. We designed a phase II trial to evaluate the efficacy and toxicity of CPT-11 plus Gemcitabine administered every 2 weeks in pts with either refractory or relapsed NSCLC. Methods: Patients with refractory or relapsed NSCLC who had experienced treatment failure with one or two prior chemotherapy regimen were considered eligible. Patients were required to have Eastern Cooperation Oncology Group (ECOG) performance status (PS) of 0 to 2 and adequate organ function; signed informed consent was also required. CPT-11 150 mg/m2 followed by GEM 1000mg/m2, both on days 1+15, recycled every 28 days. Results: Between November 2001 and February 2002, 30 patients were enrolled on this phase II trial. Twenty-seven of these patients were accessible for response, survival, and toxicity. The median age was 60.9 years (range: 37–74), and median ECOG PS was 1. Gender= 17 males/10 females, histologies; adenocarcinoma: 16, squamous: 7, others: 4. Eighteen patients had prior taxane+platinum-based treatment. Grade 3 hematologic toxicities included luecopenia (11.1%), anemia (14.8%), and thrombocytopenia (7.4%). Grade 3 nonhematologic toxicities were diarrhea (3.7%), liver injury (3.7%), dyspnea (3.7%), and nausea (3.7%). Grade 4 hematologic and non-hematologic toxicities were never encountered. Objective responses in this phase II were; PR: 5/27 (18.5%), SD: 9/27 (33.3%) and PD: 13/27 (48.1%). The median survival 7.5 months. 1-year survival was 34.9%. Conclusions: Bi-weekly GEM+CPT-11 was active and well tolerated, with an acceptable response rate and reasonable median survival time, in patients with refractory or relapsed non-small cell lung cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Melastatin expression determined by chromogenic in situ hybridization (CISH) in primary cutaneous melanoma
Authors: G. P. Linette, J. S. Ross, Q. Li, A. Dejulio, C. Sheehan, G. Bowers, L. A. Cornelius, M. C. Mihm, T. Nazir, J. A. Carlson
Journal: Journal of Clinical Oncology (2004)

7517 Background: Using a radioactive in situ hybridization method on primary melanoma (PM), loss of the melastatin (MLSN-1) mRNA expression has been found to have independent prognostic significance. In this study, we examined whether a new non-radioactive chromogenic ISH (CISH) method to evaluate melastatin expression would similarly predict PM outcome. Methods: Melastatin mRNA was evaluated by CISH on formalin fixed paraffin embedded tissues from 109 PM patients with localized disease (AJCC stages I and II). PMs were classified as having complete or partial down regulation of MLSN compared to internal control intraepidermal melanocytes. MLSN status was compared with standard prognostic factors over a mean clinical follow-up of 58 months with a range of 2 to 225 months. Results: On univariate analysis, partial or complete loss of MLSN expression, found in 32% and 27% of PM respectively, correlated with disease free survival (DFS) (p<.0001). AJCC stage (p<.0001), thickness (p<0.0001), ulceration (p=0.007), mitotic count (p=0.008), and Clark's level (p=0.04) were also significant factors. On multivariate analysis, partial or complete loss MLSN expression was the only independent prognostic factor (p<0.0001). PMs with preserved MLSN expression featured a 100% DFS in contrast to PMs with MLSN loss which had a 35% 10 year DFS. Down-regulation of MLSN expression significantly correlated with advanced AJCC stage, high mitotic count and brisk tumor infiltrating lymphocytic host response (TILs). PMs with MLSN loss and low TILs had a 5 year DFS of 51% compared to a 79% DFS for MLSN preservation and high TIL PMs (p=0.08). Conclusions: MLSN status in PM can readily be measured by CISH and reproduces past RISH findings highlighting that down-regulation of MLSN mRNA in PM is a prognostic biomarker for metastasis that is independent of other classic prognostic factors. MLSN determination by CISH has the potential to supplement current, standard prognostic assessment of primary cutaneous melanomas in routine clinical practice. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Pharmaceuticals Millennium Pharmaceuticals Millennium Pharmaceuticals
Association between salivary cytokine levels and chemoradiotherapy-induced toxicities in head and neck cancer patients.
Authors: Paolo Bossi, Paola Filipazzi, Carlo Resteghini, Rosalba Miceli, Ester Orlandi, Laura Locati, Carlo Fallai, Silvia Tana, Agata Cova, Paola Squarcina, Monica Rodolfo, Cristiana Bergamini, Roberta Granata, Aurora Mirabile, Licia Rivoltini, Lisa F. Licitra
Journal: Journal of Clinical Oncology (2012)

5555 Background: Mucositis is a common complication of chemoradiotherapy (CTRT) for head and neck cancer (HNC), linked to a balance between pro- and anti-inflammation serum cytokines. No study has yet addressed the role of salivary cytokines in influencing toxicity severity. Methods: Twenty consecutive stage III (15%) and IV (85%) HNC patients (pts) were treated with radiotherapy (64-70 Gy) plus cisplatin (n=15), carboplatin (n=4) or cetuximab (n=1). Primary tumor site was oral cavity (15%), oropharynx (55%), nasopharynx (15%), larynx or hypopharynx (15%). Unstimulated saliva samples were collected according to standardized protocols before CTRT, during (3 rd , 5 th and 7 th weeks) and two weeks after; concomitantly, mucositis grade (WHO classification), weight loss and need for feeding tube were evaluated. The salivary levels of 11 different cytokines (IFNγ, IL1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNFα and TNFβ) were analysed both in pts and in healthy donors (HD, n=10) by optimized bead-based multiplex immunoassay. The cytokine change during treatment was calculated as the difference between the mean of individual values and the baseline value. The Wilcoxon rank sum test was used for between-groups comparisons. Results: At baseline, no difference in cytokine levels was observed in pts as compared with HD, except IL8. A significant and progressive increase of IL1β, IL6, IL8, TNFα and IL10 levels was observed during treatment, with high levels persisting two weeks after treatment for all cytokines but IL1β. Significant association was shown between IL6 increase and G3/4 mucositis (p=0.009) or feeding tube need (p=0.04). The same trend was observed for TNFα. Interestingly, IL8 increase appeared to be specifically linked to weight loss (&gt;10%, p=0.003). In contrast, baseline cytokine salivary levels were not predictive of treatment-induced toxicities. Conclusions: The increase of IL6, IL8 and TNFα salivary levels occurring in HNC patients with CTRT seems to be directly associated with mucositis severity, feeding tube prevalence and weight loss. Cytokines may represent a potential new target for preventive and/or therapeutic intervention.
Effect of trastuzumab on the reduction of hormone receptor expression by neoaduvant chemotherapy in HER2-positive breast cancer
Authors: M. Hayashi, Y. Okumura, T. Ohsako, N. Arima, R. Nishimura
Journal: Journal of Clinical Oncology (2009)

11114 Background: Neoadjuvant chemotherapy (NAC) in primary breast cancer is actively used around the world. Lower ER expression is related to an increased sensitivity of NAC and ER/PgR expression decreases after NAC. Estrogen Receptor (ER) function is coordinated by crosstalk with growth factor signaling, especially that of HER2. Moreover, trastuzumab (T) has an established role in the management of HER-2 positive breast cancer in conjunction with chemotherapy. We examined the effectiveness of NAC and changes in the biological markers, particularly the ER/PgR status after NAC with or without T. Methods: Since April 2002, 143 patients with tumors ≥3 cm in diameter or lymph node metastases have received NAC and surgery. The treatment regimen were as follows; ET in 60 cases, FEC-DOC in 68 cases, and T with anthracycline and taxane in 15 cases. The items investigated were ER/PgR, Ki-67, HER2 and p53. The correlation between the changes in these factors after NAC and the treatment regimen was investigated. Results: The clinical response rate (CR+PR) was 84% in all patients. The pathological CR (pCR) rate was 7.7% in the ET, 20.9% in the FEC-DOC and 33.3% in the T regimen. The Ki67 values and ER/PgR status significantly correlated with pCR. Regarding the changes in biological markers, Ki67 values significantly decreased after NAC in all regimens. In the hormone receptor (HR) positive cases, ER and PgR positive cell rates significantly decreased (ER: 79.8% to 58.3% and PgR: 58.3% to 34.0%). However, in the arm with T, there were no significant changes in ER and PgR positive cell rates (ER: 72.7% to 69.2% and PgR: 50.3% to 38.1%). Conclusions: Lower ER/PgR expression and higher Ki-67 significantly correlated with pCR. Moreover, ER/PgR positive cell rates and Ki67 values significantly decreased after using chemotherapy. However, it appears that the T regimen may restore ER/PgR expression. Thus, ER and HER-2 expression may modify tumor biology via cross-talk even in NAC cases. No significant financial relationships to disclose.
Is there a protective role of testosterone against high-grade prostate cancer? Incidence and severity of prostate cancer in 553 patients undergoing prostate biopsy in a prospective data register.
Authors: Aksam Yassin, Mahmoud Salman
Journal: Journal of Clinical Oncology (2017)

128 Background: Major concern regarding testosterone therapy (TRT) in middle-aged and elderly men is still prostate safety or cancer Methods: 553 prostate biopsies (2008-2013) were performed at our institute. 22 patients refused biopsy. We investigated incidence and severity of PCa in three groups: hypogonadal (T ≤ 350 ng/dl) men receiving TRT, hypogonadal untreated, and eugonadal men. All groups underwent similar screening intensity of at least once per year. Biopsies were performed when indicated according to EAU guidelines. Results: In 42 hypogonadal men receiving TRT, 7 (16.7%) had a positive biopsy. Of these, 5 had a Gleason score ≤ 6 (71.4%) and 2 subjects a Gleason score &gt; 6 (28.6%). Predominant Gleason score was 3 in all 7 men (100%). Tumor grade was II in 6 (85.7%) and II-III in 1 (14.3%) men. 162 untreated hypogonadal men, 84 (51.9%) had a positive biopsy. Of these, 34 had a Gleason score ≤ 6 (40.5%) and 50 a Gleason score &gt; 6 (59.5%). Predominant Gleason score was 3 in 65 (77.4%), 4 in 17 (20.2%) and 5 in 2 (2.4%) men. Tumor grade was II in 35 (41.7%), II-III in 10 (11.9%), III in 34 (40.5%) and IV in 5 (6.0%) men. In 349 eugonadal men, 132 (37.8%) had a positive biopsy. Of these, 56 had a Gleason score ≤ 6 (42.4%) and 76 a Gleason score &gt; 6 (57.6%). Predominant Gleason score was 3 in 109 (82.6%), 4 in 22 (16.7%) and 5 in 1 (0.1%) men. Tumor grade was II in 59 (44.7%), II-III in 6 (4.5%), III in 63 (47.7%) and IV in 4 (3.0%) men. Conclusions: The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT. The severity of PCa – in terms of Staging and Grading - was significantly lower in hypogonadal patients receiving TRT. TRT may protect against high-grade PCa. Protective role of TRT against PCa must be discussed and considered in larger studies.
Complement component C9 as a new biomarker for esophageal adenocarcinoma.
Authors: Virendra Joshi, Alok Shah, Ian Brown, Clay Winterford, Michelle Hill
Journal: Journal of Clinical Oncology (2017)

19 Background: Esophageal adenocarcinoma (EAC) continues an upward trend. Mortality rate and treatment costs for EAC are very high overall and significantly increase with disease stage. Diagnosis at early stage (T1) compared to advanced stage (T3) improves 5 year survival from 20% to 80-90%. Endoscopic surveillance has been ineffective in reducing EAC. Therefore the need for better diagnostic tools for early detection.Previously we reported validation of a list of serum glycoprotein biomarker candidates for EAC in an Australian cohort (Shah et al. 2015 Mol Cell Proteomics. 14:3023-39.). Here we further evaluate the serum and tissue expression of top candidate C9 in an independent cohort from the USA. Methods: Serum samples (n=38) and FFPE tissue sections (n=34) were collected from participants with IRB approved protocol, from the Ochsner Clinic undergoing endoscopic surveillance for Barrett’s and esophageal cancer. Serum glycoprotein candidates were measured using lectin magnetic bead array-coupled multiple reaction monitoring assay (Shah et al. 2015 Mol Cell Proteomics. 14:3023-39.). Immunohistochemistry was optimised for complement component C9 antibody. Initial evaluation of 2 different antibodies gave similar results, thereafter, a polyclonal antibody from Sigma Aldrich was used. Staining was assessed by a gastrointestinal pathologist. Results: Specific glycosylated forms of 3 candidate serum biomarkers were confirmed to be significantly different between EAC and benign groups (p&lt;0.05, Kruskal-Wallis). The diagnostic value for the 3 individual markers, complement component C9, gelsolin and alpha-1-antichymotrypsin (Serpin A3) was 0.71 to 0.82 area under the receiver operating curve (AUROC). A multivariate panel consisting of 8 glycoprotein biomarkers achieved AUROC of 0.96, indicative of high diagnostic value. Immunohistochemistry of tissues detected high levels of C9 in BE and EAC compared to normal squamous epithelium. Infiltrated lymphocytes showed variable staining. Conclusions: We propose a novel candidate biomarker complement component C9 which could add to current endoscopic surveillance strategy for early detection of adenocarcinoma.
Conditional biochemical recurrence-free survival and cancer-specific mortality after radical prostatectomy at long term follow-up.
Authors: Silvia Garcia Barreras, Rafael Sanchez-Salas, Igor Nunes-Silva, Fernando P. Secin, Victor Srougi, Mohammed Baghdadi, Eric Barret, François Rozet, Marc Galiano, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2017)

55 Background: To estimate the conditional biochemical recurrence-free survival (BCR) rates and cancer-specific mortality (CSM) for men with clinically localized prostate cancer (PCa) treated with radical prostatectomy (RP) at our institution. Methods: A total of 3576 patients underwent laparoscopic radical prostatectomy (LARP) and 2619 men were treated with robotic radical prostatectomy (RARP) in the last 15 years. BCR of primary treatment was defined as PSA &gt; 0.2 ng/dl. PCa death was defined as patients who died with metastasis in an androgen independent setting. Kaplan-Meier and Cox regression methods were used to estimate the conditional survival probabilities and CSM. Results: The median follow-up was 8.49 years (IQR 4.01-12.97). A total of 92 (1.48%) patients (80 LARP and 12 RARP) died of disease. Positive surgical margins (PSM) were identified in 1202 patients (19.4%); of these, 664 (55.24%) had organ confined disease and 523 (43.51%) had extraprostatic extension (EPE). BCR-free survival rate was found significantly higher with RARP (83% vs 77% for LARP at 10 years; p &lt; 0.001). For patients with PSA &lt; 10 ng/dl BCR-free survival at 10 years was 80% vs 64% for PSA 10-20 ng/dl, and 59% for PSA &gt; 20ng/dl; p &gt; 0.001. Conditional probability of BCR after surgery 1st year was 6.7%. Those who reach the 2nd year of surgery without recurrence had a relapse probability of 4%, (cumulative probability 9.8%) That probability falls to 3.5% after the 3rd year (cumulative probability 13%), 2% after the 4th year (cumulative probability 15%) and is 2.1% after the 5th year (cumulative probability 17%). After 10 years of follow-up without recurrence, the possibility of relapse was 0.8%, (cumulative probability 21%). Men without BCR had a clinical trend of higher CSM at 10 years (7% vs 2% no BCR; p 0.06). Within the patients who develop BCR, those with BCR in the first three years of follow-up had higher CSM (9% vs 4% for BCR after 3 years; p 0.04). Conclusions: BRC free survival outcomes are affected by risk factors associated with type of surgery and prognosis in PCa. The period elapsed from RP is associated with BCR-free survival and the risk of recurrence decrease with increasing survival.
Pazopanib in chemoresistant patients with germ cell tumors (GCT): Updated results of the open-label, single-group, phase 2 Pazotest-01 trial.
Authors: Patrizia Giannatempo, Luigi Mariani, Nicola Nicolai, Elena Farè, Daniele Raggi, Manuela Marongiu, Luigi Piva, Davide Biasoni, Mario Catanzaro, Tullio Torelli, Silvia Stagni, Massimo Maffezzini, Elena Togliardi, Roberto Salvioni, Filippo G. De Braud, Alessandro M. Gianni, Andrea Necchi
Journal: Journal of Clinical Oncology (2014)

e15529 Background: Patients (pts) with GCT who fail to be cured following multiple chemotherapy (CT) courses (± high-dose CT) have an extremely poor prognosis and long-term remissions are anecdotal. Pazopanib (PZP) is a potent and selective, orally available, TKI of VEGFR1, 2, and 3, PDGFRα, PDGFRβ, and cKit. We updated the initial results of the ongoing open-label, single-group, phase 2 study which is sponsored by INT Milano. Methods: Patients failing at least 2 platinum-based CT (including high-dose CT) received PZP 800 mg/day orally until disease progression (PD) or evidence of unacceptable toxicity/side effects. All pts underwent measurement of serum tumor markers (STM), a computed tomography and a FDG-PET after 1 month and q2 months thereafter. In a Simon’s 2-stage design, the primary endpoint is 3-month progression-free survival (PFS). In stage 1, 18 evaluable patients will be accrued. If ≥ 3 pts will be progression-free at 3 months, enrolment will be extended to the 2ndstage. Results: From 06 to 12/2013, 9 patients have been enrolled, 6 in fourth and 3 in fifth-line. Median age was 38 yrs (IQR: 32-42). Eight were nonseminomas, 3 had a teratoma with malignant transformation, 3 had failed HDCT, 2 had liver metastases. Seven pts (77.8%) showed an early response after 4 weeks of treatment, and it was a marker +/- dimensional partial response (RECIST, PRm+). One had a stable disease, one a PD. In addition patients showed a densitometric response (N=3) or a reduction of FDG uptake (N=2). At +3 month-restaging, 3 patients (33.3%) were progression-free. Two patients (22.2%) had G3 AST/ALT increase and needed temporary discontinuation of PZP. One case had G2 hypertension and diarrea. Conclusions: The study has already met the PFS requirements(3 progression-free patients at +3 months) to complete the full accrual of 43 patients.The activity of pazopanib was mainly seen as a reduction of STM, as expected. However responses where also seen in patients yielding divergent histologies. Additional considerations on non-conventional response (densitometric and metabolic) assessment will require more cases. Clinical trial information: NCT01743482.
The optimal threshold of <sup>18</sup>F-FLT PET and <sup>18</sup>F-FDG PET to estimate the length of gross tumor volume in patients with squamous cell carcinoma of the thoracic esophagus verified by pathological examination
Authors: J. Yu, D. Han, Xiaojun Zhong, Dianbin Mu, Zheng Fu, Baijiang Zhan g, Limin Zhang, Weidi Zhang
Journal: Journal of Clinical Oncology (2009)

e15665 Background: To determine the optimal method of using 3-deoxy-3- 18 F-fluorothymidine (FLT) positron emission tomography (PET) to estimate gross tumor length in esophageal carcinoma, and compared with that of 18 F- fluorodeoxyglucose(FDG) PET. Methods: Twenty patients with esophageal squamous cell carcinoma treated with radical surgery were enrolled and detected by FLT PET, eighteen of them underwent FDG PET scan. Gross tumor volumes (GTVs) were delineated using seven different methods with FLT PET: visual interpretation, standardized uptake value (SUV) 1.3, SUV 1.4, SUV 1.5, and 20% of maximum standard uptake value (SUVmax), 25% SUVmax,30% SUVmax, on FLT PET imaging, and three different methods with FDG PET: visual interpretation, SUV 2.5, and 40%SUVmax on FDG PET imaging. The length of tumors on FLT PET scan were measured and recorded as L FLTvis , L FLT1.3 , L FLT1.4 , L FLT1.5 , L FLT20% , L FLT25% , and L FLT30% , and FDG PET scan were measured and recorded as L FDGvis , L FDG2.5 , and L FDG40% , respectively, and compared with the length of gross tumor in the resected specimen measured by pathological examination (L Path ). Results: The mean (±SD) L Path was 5.16±2.19cm. The mean L FLTvis , L FLT1.3 , L FLT1.4 , L FLT1.5 , L FLT20% , L FLT25% , and L FLT30% were 5.17±2.40cm, 5.55±2.43cm, 5.17±2.41cm, 4.95±2.44cm, 5.82±2.23cm, 5.32±2.31cm, and 5.04±2.28cm, respectively. Compared with the L Path , the P value were 0.971, 0.045, 0.972, 0.255, 0.066, 0.644, and 0.714, respectively. The correlation coefficients were 0.952, 0.944, 0.959, 0.948, 0.763, 0.783, and 0.800, respectively. The mean L FDGvis , L FDG2.5 , and L FDG40% were 5.41±2.27cm, 5.38±2.25cm, and 4.02±1.57cm, respectively. Compared with the L Path , the P value were 0.098, 0.085 and 0.000, respectively. The correlation coefficients were 0.984, 0.990 and 0.932, respectively. On FLT PET, L FLT1.4 , and on FDG PET, L FDG2.5 seem more approximate to L Path . The difference between L FLT1.4 and L FDG2.5 was not significantly (P=0.442), the correlation coefficients was 0.960. Conclusions: An SUV cutoff of 1.4 on FLT PET, and an SUV cutoff of 2.5 on FDG PET, provided the closest estimation of GTV length in this study No significant financial relationships to disclose.
Determining issues of importance for patients with prostate cancer: Results of a web-based study in 2,128 patients with prostate cancer for the development of a quality of life (QL) instrument, the prostate cancer symptom scale (PCSS)
Authors: R. J. Gralla, P. J. Hollen, B. J. Davis, J. A. Petersen, R. Thompson, F. Saad
Journal: Journal of Clinical Oncology (2007)

5138 Background: Identifying key issues for patients with malignancy is central to assessing QL and patient reported outcomes. This aids in evaluating the effectiveness of treatment programs for those with the disease. The immediate aim of this study was to determine content validity using a large patient panel for the PCSS, a QL measure for patients with prostate cancer. The PCSS also uses an inexpensive hand-held pocket PC to enhance feasibility. The PCSS concept is based on the LCSS (a validated lung cancer instrument). Methods: We used the established patient base of the web-based NexCura patient information resource to survey registered patients with prostate cancer. Demographic stratifications included stage of disease, prior radical prostatectomy, and current treatment (none, hormonal, non-hormonal). 2,128 patients completed the anonymous web-conducted survey, performed over a 3-day period. Patients were asked to rank 18 issues on a 5-point scale assessing the importance of each item. Issues included general, prostate-specific, psychosocial and summative items. Results: The 10 highest (and 2 lowest) ranked items are seen in the table ; results are described by the percent of patients choosing the top category (very important) and the top 2 rating categories of importance. Ratings by disease subsets (such as NED or metastatic disease; hormonal or non-hormonal treatment) were quite similar to results found for the whole group, as listed in the table . Conclusions: These results represent the largest survey of patient concerns in prostate cancer and support using computer-assisted survey technology to assess such information in all malignancies to obtain patient input rapidly from large patient samples. Strong support for content validity for the PCSS was obtained. [Table: see text] No significant financial relationships to disclose.