tbuckley/cabot-search huggingface dataset:
Cryoablation compared with radiofrequency ablation and microwave coagulation therapy for the local control of primary hepatocellular carcinoma.
Authors: Shigenori Ei, Minoru Tanabe, Taizo Hibi, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Yuta Abe, Hiroshi Yagi, Koji Okabayashi, Masanori Odaira, Yoshie Kadota, Tomonori Fujimura, Yusuke Katsuki, Masayuki Tanaka, Rina Tsutsui, Go Wakabayashi, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2013)

286 Background: Although cryoablation (Cryo) has been advocated as an effective local treatment for hepatocellular carcinoma (HCC), data are lacking regarding its outcomes in comparison with radiofrequency ablation (RFA) and microwave coagulation therapy (MCT). The aim of this study was to clarify the benefits and disadvantages of each modality for primary HCC. Methods: We reviewed outcomes of 120 patients with primary HCCs (&lt; 5cm) who underwent local treatment (Cryo: n = 55 and RFA/MCT: n = 65) between 1998 and 2011. The primary endpoint was local recurrence free survival (LRFS). The secondary endpoints were complication rates and the length of hospital stay. Results: Age, sex, Child-Pugh score, and background liver disease were identical between both groups. The Cryo group had larger tumors (mean ± standard error tumor size: Cryo 2.55 ± 0.75 cm vs. RFA/MCT 1.96 ± 0.72cm, p &lt; 0.001). The LRFS was higher in the Cryo group than in RFA/MCT group (2270.0 ± 240.8 days vs. 1940.7 ± 269.5 days: p = 0.116). The Cox proportional hazards multivariate analysis revealed that Cryo as the treatment of choice was an independent predictive indicator of improved LRFS (HR, 0.403 [95% CI: 0.202−0.807], P = 0.010). On the contrary, tumor size (for each 1 cm increase, HR, 1.635 [95% CI: 1.038–2.574], p = 0.034) and Child-Pugh score ≥ 6 (HR, 2.166 [95% CI: 1.179 – 3.979], p = 0.013) were negative prognostic factors for LRFS. Subgroup analysis showed that the LRFS for tumors ≤ 2 cm was similar between the 2 groups. However, if the tumor size was greater than 2 cm, the LRFS of the Cryo group was superior to RFA/MCT (2400.0 ± 287.4 days vs. 1177.9 ± 366.5 days: p = 0.004). The complication rates (Cryo 10.9% vs. RFA/MCT 10.8%: p = 0.980) and the length of hospital stay (9.45 ± 5.33 days vs. 9.52 ± 5.90 days: p = 0.947) were similar in both groups. No mortality was observed in the entire cohort. Conclusions: Cryo provides significantly higher chance of local control for primary HCCs compared with RFA/MCT, particularly if the tumor size exceeds 2 cm. Associated risks are at least equivalent to those of RFA/MCT even in patients with marginal to poor liver function. Cryo is a promising local ablative option in an era of rising incidence of HCC.
MicroRNA as novel blood-based biomarkers in clear cell renal cell carcinoma.
Authors: A. Ari Hakimi, Anders Jacobsen, Nina Mikkilineni, Brandon Fiegoli, Sara Blass, Yevgeniy Grigoryev, Agnes Viale, Nicholas D. Socci, Martin Henner Voss, Robert John Motzer, Victor E. Reuter, Jonathan A. Coleman, Paul Russo, James Hsieh
Journal: Journal of Clinical Oncology (2013)

375 Background: MicroRNAs (miRNA) are short, non-coding RNAs involved in post-transcriptional gene regulation. Several reports have assessed their role as blood based biomarkers given their tissue and cancer-specific expression. Using an integrative approach we sequenced the miRNA transcriptome of the plasma of several clear cell renal cell carcinoma (ccRCC) patients both before and after surgery as well as several controls. Methods: We performed next generation miRNA sequencing (miRNAseq) on eight pairs (pre- and post-operative plasma samples) and four non-cancer controls to identify potential biomarker candidates. We further integrated our data with the miRNAseq tumor data from the Cancer Genome Atlas (TCGA) study to determine whether plasma miRNA levels are representative of tumor miRNA expression in ccRCC. Results: Overall, 930 unique miRNAs were detected, including 272 at greater than or equal to 10 read counts. There was a global shift of miRNA expression toward the non-cancer controls in the postoperative samples compared to preoperative. We further identified several stably expressed miRNAs across all samples and controls including miR-16, miR-191, and miR-103. We also identified several potential biomarker candidates by looking at differential expression both in terms of preoperative and postoperative status, as well as tumor vs. control including miR-378 and miR-660. Intriguingly, the plasma miRNA expression patterns showed no relationship to the tumor expression patterns using the TCGA samples. Conclusions: Plasma miRNA expression patterns are consistently altered in ccRCC and, following surgery, globally revert to the non-cancerous levels of the controls. Several biomarker candidates have been identified and a panel is undergoing validation in larger cohorts. Plasma miRNA levels do not appear to reflect tumor levels in ccRCC.
A randomized placebo-controlled phase II study with the cancer vaccine candidate IGN101 in patients with epithelial cancers
Authors: G. Himmler, A. Settaf, F. Groiss, N. Eller, M. Salzberg, M. Kundi, H. Eckert, H. Loibner, H. Samonigg
Journal: Journal of Clinical Oncology (2005)

2555 Background: IGN101 is a vaccine designed for therapeutic vaccination against cancers of epithelial origin. It consists of 0.5 mg alum-adsorbed murine monoclonal antibody 17-1A as vaccine antigen to trigger an immune response and has been shown in phase I to reduce the number of circulating EpCAM-positive tumor cells. Methods: A 1:1 prospective randomized double-blind placebo-controlled phase II trial was conducted in 240 patients (pts) with epithelial cancers Stage III or IV. Objectives were to assess effects of IGN101 on survival of the whole study population but also to analyse in an exploratory way the survival effects for the different tested indications. Primary endpoint was overall survival (OS), secondary endpoints included safety, tolerability and immunogenicity. Vaccinations with IGN101 or placebo (alum) were given on days 1, 15, 29 and 57 and in weeks 16, 24, 32, 40 and 68. Concomitant standard therapies were permitted. Pts were recruited from Sept. 01 until July 03. Results: On intention-to-treat (ITT), 239 pts were included. 163 pts had CRC, thereof 95 stage IV. 32 pts had stage III or IV upper GI-tract cancer, 38 pts had stage III or IV NSCLC, 6 pts had liver or bile-duct carcinoma. Groups were well balanced regarding age, sex, Karnofsky Index and concomitant therapies. For the whole ITT population, no difference in OS was seen. A trend for prolonged survival was seen in stage IV CRC pts (ITT) during the first year (12 months overall survival 48.8% Placebo vs. 60% IGN101, p = 0.28). A statistically significant survival prolongation was observed in the 53 stage IV rectal cancer pts (ITT): For the IGN101 group, median survival was 415 days, compared to 253 days for placebo (P = 0.037). 1-year survival was doubled from 29,5% for placebo to 62% for IGN101. Use of concomitant chemotherapy (CT) had no effect on survival. Vaccinations with IGN101 were well tolerated. Almost all pts of the IGN101 group mounted an antibody response to the vaccine antigen. Conclusions: Whereas the effect observed in the overall colorectal cancer stage IV group was not statistically significant (potentially due to sample size), vaccination with IGN101 however significantly prolonged survival of metastatic rectal cancer pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration igeneon AG igeneon AG igeneon AG
Benefit of chemotherapy (ctx) in elderly patients (pts) with advanced pancreatic adenocarcinoma (PC): A population-based analysis.
Authors: MinYuen Teo, Sandra Deady, Linda Sharp, Raymond S. McDermott
Journal: Journal of Clinical Oncology (2014)

310 Background: Benefit of ctx in elderly PC is unclear as they are under-represented in trials and most reports are retrospective series from academic centres. This population based study sought to examine the role of ctx in the elderly PC. Methods: Pts with diagnosis of PC between 1998 and 2010 inclusive who did not receive radical resection were identified from National Cancer Registry of Ireland database. Pts were divided into two age groups: ≥70 vs &lt;70, and stratified based on metastatic status: M0 vs M1. Median overall survival (OS) was estimated with Kaplan-Meier method and hazard ratios (HR) with Cox regressional analysis. Results: A total of 4,509 pts were identified, of whom 2,875 (64%) were ≥70 yrs. For the entire group, 16% were staged M0, 42% were staged M1 and 42% didn't have documented staging (Mx). 16% received ctx, 5% chemoradiotherapy (crt) and 79% no cancer directed therapies. More pts ≥70 were Mx compared to &lt;70 (48% vs 30%, p&lt;.01); Mx pts were less likely to receive treatment than M0/M1 (88% vs 73% vs 73%, p&lt;.01). Pts ≥70 were also less likely to receive any treatment (p&lt;.01) (Table). Comparing the ≥70 and &lt;70 groups, median OS (in months) for M0 who received ctx were 6.0 vs 7.3 (HR 1.28 [95% confidence interval 0.85-1.89], p=.24); received crt were 7.0 vs 9.7 (HR 0.95 [0.42-1.88] p=.89) and no treatment were 3.0 vs 3.5 (HR 1.03 [0.84-1.29] p=.75); median OS for M1 who received ctx were 2.4 vs 3.4 (HR 1.21 [0.97-1.49] p=.09), crt were 4.3 vs 6.0 (HR 1.69 [0.89-3.03] p = .11) and none were 1.2 vs 1.4 (HR 1.11 [1.00 – 1.24] p=.06). Regardless of age or M stage, cxt and crt conferred superior OS as compared to no treatment (Table). Conclusions: We observed a disparity in diagnostics and delivery of treatment to older pts with PC. Pts ≥70 who were treated benefited similarly to younger pts. Such therapeutic nihilism should be addressed in a systematic fashion. [Table: see text]
Randomized phase II trial of docetaxel (Doc) and prednisone (Pred) with or without AZD2171 (cediranib), in chemotherapy-naive, metastatic castrate-resistant prostate cancer (mCRPC) (NCI 7451).
Authors: Elisabeth I. Heath, Heather Dorothy Mannuel, Glenn Liu, Primo Lara, J. P. Monk, Thomas W. Flaig, Amado J. Zurita, Ulka N. Vaishampayan, Philip J. Stella, Daryn W. Smith, Kimberlee Dobson, Arif Hussain, Anas Al-Janadi, S. Percy Ivy, Lance K. Heilbrun
Journal: Journal of Clinical Oncology (2013)

38 Background: Cediranib + Doc were shown in a phase I trial to be feasible, with early evidence for efficacy in mCRPC patients (pts). A multi-center randomized Phase II screening trial of Cediranib+Doc+Pred (Arm A) vs. Doc+Pred (Arm B) was initiated in mCRPC pts. Methods: mCRPC pts with no prior chemotherapy were eligible. All received Doc at 75 mg/m 2 IV q 3 weeks and Pred 5 mg po bid. Cycle length was 21 days. Arm A pts also received Cediranib at 30 mg po daily. The primary endpoint was 6-month progression-free survival (PFS). We hypothesized 6-month PFS rates of 0.70 on Arm A and 0.50 on Arm B. Secondary endpoints included toxicity, PSA response, and RECIST response. Here we report the toxicity and PSA response data. Results: Of 58 pts enrolled, 57 were treated (29 Arm A, 28 Arm B). Median age = 68 years (range 51-84); 33% African-American, 63% Caucasian; median baseline PSA136 ng/mL (range 0.12 – 3,650); 57% had Gleason grade 8-10; and 40% had both bone/ visceral disease. Median nadir PSA was 10.5 ng/mL (range 0.10 – 1,484) in Arm A, and 25.9 ng/mL (range 0.00 – 2,076) in Arm B. Median number of cycles (range): Arm A = 9 (0 - 31); Arm B = 6.5 (1-39 ). 68% pts in Arm A required a dose reduction of at least one Cediranib dose level. Doc dose was reduced in 45% pts on Arm A and in 18% pts on Arm B. Primary grade 4 toxicity was neutropenia (11 [38%] pts A; 5 [18%] pts B), which prompted Cediranib dose reduction. Grade 3 toxicities included fatigue (9 (31%) A, 1 (4%) B); hypertension (8 (28%) A, 1 (4%) B); anemia (6 (21%) A, 2 (7%) B); neutropenia (4 (14%) A; 6 (21%) B); diarrhea (3 (10%) A, 1 (4%) B); deep vein thrombosis (2 (7%) A, 1 (4%) B); and pulmonary embolism (1 (3%) A). An amendment reduced Cediranib to 20 mg daily dose. PSA decrease ≥ 90% at nadir occurred for 13/29 = 45% on Arm A, and 6/28 = 21% on Arm B. PSA decrease ≥ 50% at nadir occurred for 19/29 = 66% on Arm A, and 17/28 = 61% on Arm B. Clinical partial response rates were 8/15 = 53% on Arm A and 3/9 = 33% on Arm B. Conclusions: The addition of Cediranib to Doc/Pred has increased toxicity but may be associated with higher rates of PSA response and clinical response in mCRPC patients. PFS results will be reported. Clinical trial information: NCT00527124.
Intensity modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience
Authors: W. C.-Y. Chen, M. J. Zelefsky, D. G. Pfister, S. L. Berry, D. H. Kraus, S. L. Wolden
Journal: Journal of Clinical Oncology (2005)

5541 Background: We previously demonstrated that IMRT significantly improves radiation dose distribution over 3-dimensional (3D) planning for nasopharynx cancer (NPC) and reported positive early clinical results. We now evaluate whether IMRT has resulted in improved outcomes for a larger cohort of NPC patients with longer follow-up. Methods: Since 1998, all 74 patients with newly diagnosed, nonmetastatic NPC were treated with IMRT using accelerated fractionation to 70 Gy; 59 received a hyperfractionated concomitant boost and more recently 15 received once daily treatment with dose-painting. With the exception Stage I disease (n=5) and patient refusing (n=1), 69 patients received concurrent and adjuvant platinum based chemotherapy similar to Intergroup 0099 trial. Results: Patient characteristics: median age 45; 32% Asian; 72% male; 65% WHO III; 51% Stage T3/4, 47% N2/3, and 47% Stage IV. Median follow up is 33 months. The 3-year actuarial rate of local control is 89% and regional control is 95%. Freedom from distant metastases, progression-free survival, and overall survival are 78%, 64% and 82% respectively. Six of the seven local failures were exclusively within the 70Gy volume and one was both within and outside the target volume. There is a trend for improved local control with IMRT when compared to local control of 79% for patients treated prior to 1998 with 3D planning and chemotherapy, but this is not statistically significant (p=0.18). Six months post-therapy, 21%, 13%, 15% and 0% of patients with follow-up audiograms (n=24 patients, 48 ears) had Grade 1, 2, 3, and 4 sensorineural hearing loss, respectively. For patients with >1 year follow-up (n=59), rates of long-term xerostomia were: 26% none, 42% grade 1, 32% grade 2, and zero grade 3. Conclusions: The lack of significant improvement in local control with IMRT and pattern of primary site failure within the target volume suggest a need for a higher biological dose to gross tumor. Rates of severe (grade 3–4) ototoxicity and xerostomia are low with IMRT due to normal tissue protection. Distant metastases are now the dominant form of failure emphasizing the need for improved systemic therapy. No significant financial relationships to disclose.
Utility of prostate multiparametric MRI (mpMRI) for recurrent prostate cancer after radiation therapy and cryotherapy.
Authors: Evan Kovac, Andrei Purysko, J. Stephen Jones, Cristina Magi-Galluzzi, Eric A. Klein, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2016)

71 Background: We evaluated the accuracy of mpMRI for identifying locally recurrent prostate cancer after primary radiotherapy and cryotherapy. Methods: Between 2009-2015, 61 patients with evidence of rising PSA after external-beam radiotherapy (EBRT) (N = 33), brachytherapy (N = 6), and cryotherapy (N = 22) were evaluated for locally recurrent prostate cancer with mpMRI and prostate biopsy. Of these patients, 6 (10%) received androgen deprivation therapy (ADT) in combination with EBRT for a median of 24 months. Three of the cryotherapy patients received prior EBRT. Patients were identified from a prospective mpMRI database. All patients with a lesion of interest (LOI) underwent a ≥ 12-core, post-mpMRI cognitive fusion prostate biopsy. We excluded 16 patients with mpMRI who did not undergo prostate biopsy (5 positive, 11 negative). Results: Median age was 70 (IQR: 64-77). The median time from primary treatment to mpMRI was 5 years (IQR: 3-9) and the median PSA at mpMRI was 3.6 ng/mL (IQR: 2.1-5.5). Median prostate volume was 18.8 cc (IQR: 11.0-28.0 cc). mpMRI revealed lesions of interest (LOI) in 39 (64%) and 41 (67%) had biopsy-proven local recurrence. Of the 22 patients with negative mpMRI, 8 (36%) had a positive biopsy, with a median prostate volume of 19 cc, median maximum cancer length of 5 mm, median PSA of 2.5 and biopsy Gleason scores 3+3 (N = 1), 4+3 (N=2), 5+4 (N = 1), 5+5 (N = 1) and ungraded due to treatment effect (N = 3). Of the 39 patients with LOI on mpMRI, 33 (85%) had a positive biopsy. Table 1 summarizes the mpMRI and biopsy results. The sensitivity, specificity, PPV and NPV of mpMRI to predict cancer diagnosis at biopsy was 80.5%, 70.0%, 84.6% and 63.6%, respectively. On univariate analysis, gland size (p=0.367), PSA (p=0.872), biopsy Gleason score (p=0.892) and primary treatment modality (p=0.177) did not significantly predict discrepancy between mpMRI and biopsy findings. Conclusions: mpMRI reliably identifies prostate cancer recurrence after primary radiation therapy and cryoablation. [Table: see text]
Neoadjuvant radio chemotherapy in esophageal squamous cell carcinoma: Early results analysis of a 5-year experience.
Authors: E. J. Lima da Costa, H. Santos Sousa, T. Bouca-Machado, B. Caldeira, C. Paredes, J. Pinto-de-Sousa, A. Gouveia, J. Sousa Rodrigues, J. Costa-Maia
Journal: Journal of Clinical Oncology (2011)

141 Background: Optimized survival in oesophageal squamous cell carcinoma (OSCC) depends on complete surgical resection: prognostic impact of well-standardized techniques and per operative management in experienced groups has proven to be a key aspect. Multimodal treatment (MT) options are still controversial but particularly important in locally advanced disease apparently allowing better resectability. We perform an early evaluation of a MT protocol in locally advanced OSCC. Methods: Survival and clinical response analysis of a cohort of pts selected between 01/01/2002 and 31/12/2007. Criteria: Locally advanced OSCC (T3/4); No distant metastases; Negative bronchoscopy; Age under 76y; No other known cancer; Surgical feasibility. Pts underwent a 5 week MT: Chemo – taxotere 20 mg/m 2 IV, cysplatin 20 mg/m 2 IV, 5-FU 425 mg/m 2 iv (days 1,8,14,22 and 29); Radio- 40 Gy (days 1-5, 8-12, 14-19, 22-26 and 29-34) followed by surgery within 4 weeks. Results: 57 pts (38% of all admitted) 8 fem and 49 male, aged &lt; 50y = 11, 51-65y = 30 and &gt; 65y = 16. Response: Complete pathological remission = 13; Partial clinical response with downstaging = 15; Minimal / no clinical response = 14; Disease progression / no surgery: 15. From the 42 pts operated, an “en bloc” osophagectomy with extended lymphadenectomy was possible in 36. The overall mean follow-up for resected pts was 16.9 months (CI 95%: 10.9-22.8). The median survival was 18 months for resected patients (CI 95%: 8.7-27.3) in contrast with 7 for all candidates to MT. There was a statistically significant difference in the survival of the 4 groups divided according to their response to MT, with clear advantage of the complete pathological remission achievers. Conclusions: Short follow-up and series size does not allow definite conclusions. It seems nevertheless that only the group of full pathological remission and probably those that obtain a downstaging of their disease benefit from MT. Histopathological or molecular markers are required to identify target pts for neoadjuvant radio chemotherapy. No significant financial relationships to disclose.
Transplant CD34+ Cell Dose Affects Outcomes Following Allogeneic Peripheral Blood Stem Cell Transplantation from a Matched Unrelated Donor.
Authors: Ryotaro Nakamura, Joycelynne Palmer, Roberto Rodriguez, Pablo Parker, David Senitzer, Anthony Stein, Josheph Rosenthal, Sean Wang, Jeffrey Schriber, Stephen J. Forman, Auayporn Nademanee
Journal: Blood (2005)
Predictive value of bone scan index using computer-aided diagnosis system for bone scans in patients receiving first-line hormone therapy for metastatic hormone-sensitive prostate cancer.
Authors: Yasuhide Miyoshi, Masato Yasui, Shuko Yoneyama, Koichi Uemura, Takashi Kawahara, Yusuke Hattori, Jun-ichi Teranishi, Jun-ichi Ohta, Yumiko Yokomizo, Masataka Taguri, Hiroji Uemura, Masahiro Yao
Journal: Journal of Clinical Oncology (2016)

225 Background: Recently, the CHAARTED and STAMPEDE studies showed a survival benefit for docetaxel when started with androgen deprivation therapy (ADT) in men with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). While GETUG-AFU 15 failed to demonstrate a survival benefit of early chemotherapy. New biomarker for select the candidate for early chemotherapy in mHSPC is warranted. The objective of this study is to evaluate the bone scan index (BSI) using computer-aided diagnosis system for bone scans for predictive factor in patients receiving ADT as first-line hormone therapy for mHSPC. Methods: We identified consecutive 85 mHSPC patients treated with maximum androgen blockade (MAB) as first-line hormone therapy. We analyzed the correlations between progression-free survival (PFS) of MAB and clinicopathological characteristics, including patients’ age, initial PSA levels, Gleason scores, clinical TNM stage, hemoglobin (Hb), lactase dehydrogenase (LDH), c-reactive protein (CRP), and bone scan index (BSI). Statistical analyses were assessed using cox proportional hazards regression models. Results: The median patients’ age was 73 and the median follow-up duration was 11.3months. The median initial PSA value was 270 ng/ml. Median BSI was 2.7 % (range: 0.0-14.6). Clinical or PSA progression occurred in 55 (64.7%) patients. The median time to progression was 12.9 months. In multivariate analysis, three significant risk factors for PFS were identified; patients’ age ( &gt; 73 years old vs ≤ 73; HR 0.53, p = 0.038), initial PSA levels ( &gt; 270 ng/mL vs ≤ 270; HR 0.53, p = 0.038), and BSI ( &gt; 2.7 vs ≤ 2.7; HR 3.0, p &lt; 0.000). We stratified the patients into two cohorts with low risk (0-1 risk factor present) and high risk (2-3 risk factors present). We found a significant difference in PFS among risk groups (median PFS 15.3 months vs 8.5, p &lt; 0.000). Conclusions: Patients’ age, initial PSA levels, and bone scan index were the significant predictive factors for MAB as first-line hormone therapy in patients with mHSPC. These findings might support the decision-making of induction of early chemotherapy for mHSPC.