tbuckley/cabot-search huggingface dataset:
A phase II trial using carbon ion radiotherapy (C-ion RT) for prostate cancer
Authors: H. Ishikawa, H. Tsuji, T. Kamada, T. Yanagi, M. Wakatsuki, J. Shimazaki, H. Tsujii
Journal: Journal of Clinical Oncology (2005)

4630 Background: Carbon ion therapy (C-ion RT) is a heavy charged particle radiotherapy characterized with well-localized dose distribution and relatively higher biological effects compared with X-ray. A phase II clinical trial of hypofractionated C-ion RT for prostate cancer was performed in order to clarify the efficacy and safety of recommended dose which was obtained by the results of the preceded phase I/II studies. Methods: Primary endpoint of this study is biochemical relapse free survival (bNED) and secondary ones are local control and normal tissue morbidities. Between April 2000 and November 2003, histologically confirmed 175 patients with previously untreated and localized T1b-T3b prostate cancer were enrolled in this study. All patients were treated with C-ion RT using the recommended dose of 66.0 GyE in 20 fractions. For 33 patients of a low risk group (Stage ≤ T2a and PSA < 20ng/ml and Gleason score ≤ 6), C-ion RT alone was performed and the remaining 142 patients of a high risk group received combination of C-ion RT and hormonal therapy. Results: Biochemical relapses were observed in 16 patients and 4-year biochemical relapse free survival rate was 87.7%. Local control was obtained in all but one patients. By the date of the analysis, 4 patients died of prostate cancer and 3 died of intercurrent diseases. The rates of overall survival and cause-specific survival at 4 years in a low risk group were 95.7% and 100%, respectively, whereas the corresponding rates in a high risk group were 89.2% and 91.9 %, respectively. Incidences of radiation morbidities in the rectum and the genitourinary system were quite low. There was no grade 3 or higher morbidities and grade 2 rectal and urinary morbidities developed in 3 (1.7 %) and 9 (5.1%) patients, respectively. Conclusions: Hypofractionated C-ion RT could achieve excellent outcomes for prostate cancer with a low incidence of normal tissue damages. Based on low α/β of prostate cancer, a further hypofractionated regimen (16 fractions) has been tested since last year. No significant financial relationships to disclose.
Efficacy of a mitochondrial toxin, F16, in a multi-ATP-depleting regimen + chemotherapy on human breast cancer (MDA-MB-468) xenografts
Authors: D. S. Martin, A. Alfieri, J. Koutcher, V. Fantin, D. Spriggs, L. Norton
Journal: Journal of Clinical Oncology (2004)

2096 Background: : Chemotherapy is enhanced by multi-ATP-depleting therapy (Cancer Res. 60: 6776, 2000). Malignant tumors generally increase ATP production to increase cell division. In general, tumors make and consume (deplete) more ATP than normal tissues. If ATP production is equally inhibited in normal and tumor tissues, high ATP consumption (depletion) in tumors should deplete ATP to cytocidal levels, whereas the lower ATP consumption in normal cells should reduce ATP to tolerable levels. This rationale requires multiple ATP inhibitors inhibiting multiple biochemical pathways that produce ATP. Methods: Alanosine (AL), inhibitor of AMP synthesis, + 6-methylmercaptopurine riboside (MMPR), inhibitor of purine synthesis, preceded by PALA, a pyrimidine inhibitor; acronym, PALM. F16 blocks ATP synthesis by selectively accumulating in mitochondria of responsive breast cancers (Cancer Cell 2:29, 2002). Results: F16 alone was not effective. Taxotere alone (TXT), at MTD40, affects 100% PR of tumors. The addition of PALM (P100 AL250 M150), or PALM + F16 10, effects the same 100% P.R. at half the TXT dose (TXT20), suggesting clinical benefit at reduced normal tissue toxicities. Follow-up (120 days) demonstrates substantial tumor recurrence (43–50%) in Groups 1 and 2, and minimal recurrence (17%) in Group 3. Conclusions: A multi-ATP-depleting regimen (PALM + F16) + chemotherapy augments tumoricidal capability. Chemotherapy is at markedly lower doses, strongly suggesting lower toxic side-effects in the clinic. No significant financial relationships to disclose.
Long-term survival following nephrectomy for renal cell carcinoma: The 15 year University of California-Los Angeles experience
Authors: J. S. Lam, R. H. Goel, A. J. Pantuck, R. A. Figlin, A. S. Belldegrun
Journal: Journal of Clinical Oncology (2006)

14532 Background: Significant advances in the diagnosis, staging, and treatment of patients with renal cell carcinoma (RCC) during the last 2 decades have resulted in improved survival of a select group of patients and an overall change in the natural history of the disease. We describe the pathologic characteristics and long-term survival in patients treated for localized and metastatic RCC at a single tertiary care institution. Methods: Between 1990 and 2005, 1431 patients diagnosed with a renal mass underwent surgical resection and were evaluated for differences in clinicopathologic characteristics and survival based on the University of California-Los Angeles Integrated Staging System (UISS). Data were analyzed using standard statistical methods. Results: Following surgical resection, RCC was found in 1269 patients at pathologic evaluation. Of these patients, 473 had evidence of metastatic dissemination at time of surgery. The primary tumor in patients with metastatic disease was more likely to be clear cell (78.8% vs. 72.9%, p = 0.02), collecting duct (1.3% vs. 0.1%, p = 0.01), or undifferentiated (4.8% vs. 1.6%, p = 0.002) RCC, and less likely to be papillary (12.0% vs. 18.7%, p = 0.002) or chromophobe (3.1% vs. 6.7%, p = 0.006) RCC compared to patients with non-metastatic disease, respectively. The 2-year, 5-year, and 10-year survival was significantly higher in non-metastatic patients compared to patients with metastatic disease present at time of surgery (87.0% vs. 42.4%, 70.0 vs. 21.8%, 50.0% vs. 16.5%, p &lt; 0.001, respectively). Conclusions: Over the last 15 years, patients with non-metastatic disease at the time of surgery have improved survival rates and are more likely to have papillary or chromophobe primary tumors than patients with metastatic disease. UISS stratification of patients with RCC provides a unique tool for risk assignment and outcome analysis to help determine follow-up regimens and eligibility for clinical trials. [Table: see text] No significant financial relationships to disclose.
Dynamic FDG-PET/CT as an indicator of tumor aggressiveness and patient outcome in pancreatic cancer.
Authors: R. Epelbaum, O. Israel, R. Haddad, N. Sikorski, A. Frenkel
Journal: Journal of Clinical Oncology (2010)

e14526 Background: FDG-PET/CT is being extensively used for diagnosis and staging of various malignancies, including pancreatic cancer. Attempts have been made to quantitate FDG uptake as an index of tumor aggressiveness and prognosis. The objective of this study was to assess the potential role of a full quantitative dynamic PET model for measurements of FDG uptake kinetics in patients with pancreatic cancer in search for an accurate index of tumor aggressiveness and predictor of survival. Methods: Dynamic PET was performed using 28 frames over a 60 minutes period, and was followed by a whole-body PET. Data measurements was based on two-compartment model, and the calculated variables were VB (fractional blood volume in the target area), k1,k2 (kinetic parameters for the membrane transport), k3,k4 (parameters related to phosphorylation and dephosphorylation of intracellular FDG) and global influx of FDG. Univariate and Cox regression multivariate survival analysis were done, including the kinetic variables, standardized uptake value and clinical parameters such as stage of disease, tumor location and age. Results: Seventy-one patients with FDG-avid adenocarcinoma of the pancreas were recruited, 27 patients with localized tumor (11 patients underwent pancreatectomy and 16 had localized nonresectable tumor) and 44 with metastatic disease. The only significant variable for overall survival (OS) in patients with localized disease was FDG influx: median OS was 5 and 6 months for patients with high FDG influx (above the median value of 0.033 min-1), resected and non-resectable, respectively, while it was 15 and 19 months for patients with low FDG influx, nonresectable and resected, respectively (p < 0.04). Significant prognostic kinetic variables for all patients were FDG influx, VB and k1. Median OS for patients with high FDG influx, low VB and high k1 was 3 months, as opposed to 14 months in patients with low FDG influx, high VB and low k1, irrespective of stage and resectability. Conclusions: Absolute quantitation of FDG kinetics by dynamic PET in patients with newly diagnosed cancer of the pancreas may represent a potential tool for defining aggressiveness of disease and for tailoring treatment to individual patients. No significant financial relationships to disclose.
Phase I/II trial of vaccine therapy with tumor-RNA transfected dendritic cells in patients with advanced malignant melanoma
Authors: S. Aamdal, J. Kyte, S. Dueland, L. Mu, H. P. Gullestad, T. Ryder, M. Hauser, G. Kvalheim, S. Sæbøe-Larsen, G. Gaudernack
Journal: Journal of Clinical Oncology (2005)

2540
Autoimmunity predicts prolonged survival in colon cancer patients undergoing GOLFIG biochemotherapy
Authors: P. Correale, P. Tagliaferri, F. Montagnani, C. Remondo, C. Intrivici, F. Fulfaro, K. Y. Tsang, P. Tassone, M. S. Rotundo, S. Venuta, G. Francini
Journal: Journal of Clinical Oncology (2007)

14542 Background: A multi-center phase II trial has been designed to evaluate toxicity, anti-tumour and immune-biological activity of the bio-chemotherapy GOLFIG regimen in advanced colorectal cancer (A-CRC). Methods: The trial involved 46 patients (34/46 2 nd line or more). The biweekly GOLFIG regimen consisted of gemcitabine (1,000 mg/m 2 , day 1), oxaliplatin (85 mg/m 2 , day 2), levofolinic acid (100 mg /m 2 , day 1,2) and 5-FU (400 mg/m 2 as a bolus, and 800 mg/m 2 as 24 hour infusion, days 1,2) followed by sc GM-CSF (100 μg, days 3 to 8) and sc IL-2 (0.5 X 10 6 IUs twice a day, days 9 to 14). Results: GOLFIG regimen was well tolerated and resulted very active (ORR = 56.5%; disease control = 91.3%), fulfilling the pre-selected (40–60%) target of activity, with a promising TTP [12.26 months, 95% CI; 9.2–15.2 mo.] and OS [18.76 months, 95% CI; 15.2–22.3 mo.]. We detected a significant rise in lymphocyte number and colon cancer-specific cytotoxic T cells (CTLs) paralleled by a reduction in suppressive T-regulatory CD4 + CD25 + FoxP3 + lymphocytes -T reg . Self-limiting autoimmunity (AI) occurred in 6 (14%) patients. 1 patient developed cutaneous lesions, with pathological diagnosis of Discoid Lupus Erythematosus (DLE), while 5 other presented a mono / oligoarticular arthritis mainly localized at the knees, elbows, shoulders and fingers with signs of synovitis (pain and swelling) paralleled by a significant increase of inflammatory markers (ESR, C-RP and rheumatoid factor). Subgroup analysis disclosed a mean time to progression of 23.8 months (95% CI; 12.1–35.56 mo.) and an overall survival of 31.83 months (95% CI; 19.9–43.7 mo.) in the 6 AI patients, significantly longer than in patients who did not develop AI [TTP and OS respectively 10.52 (95% CI; 7.7–13.3) and 16.8 months (95% CI; 13.3–20.2)], P ≤ 0.0039 and 0.0080. 5/6 AI patients are still alive and 3 have so far achieved a survival of 37, 41 and 50 months. Conclusions: The GOLFIG regimen exerts immunological and anti-tumour activity and has manageable toxicity in A-CRC. The occurrence of AI is predictive of a favourable outcome. These results provided the rationale for a presently ongoing phase III trial aimed to compare the efficacy of GOLFIG vs. FOLFOX-4 regimen as first line treatment in A- CRC patients. No significant financial relationships to disclose.
Safety and immunogenicity of the optimized cryptic peptide TERT<sub>572Y</sub> in patients with advanced malignancies: A Phase I clinical study
Authors: K. Kosmatopoulos, E. Bolonaki, S. Cornet, E. Nikoloudi, P. Kanellou, G. Millaki, I. Miconnet, C. H. Christophillakis, M. Spiropoulou, V. Georgoulias, D. Mavroudis
Journal: Journal of Clinical Oncology (2005)

2579 Background: TERT572Y, an optimized cryptic peptide homologous to TERT induces efficient antitumoral T cell cytotoxic immunity but not autoreactivity in vivo in HLA-A*0201 transgenic mice and healthy blood donors and prostate cancer patients (J. Clin. Invest., 2004, 113,425). A phase I trial evaluating the safety and immunogenicity of the cryptic TERT572Y peptide was conducted in HLA-A*0201 cancer patients. Methods: Nineteen patients with chemotherapy refractory and progressing malignant tumors were enrolled in the study. The vaccination protocol consisted of two injections of optimized TERT572Y peptide followed by four injections of native TERT572 peptide. Peptides were injected emulsified in Montanide ISA51. Patients were vaccinated with escalated doses of peptide ranging from 2 to 6 mg. Toxicity and peptide-specific immune responses were evaluated. Results: Fourteen patients completed the entire vaccination program. Only grade I toxicity was observed, affecting 13 of the 19 patients. TERT572Y-specific cytotoxic T cells were detected in the peripheral blood of 13 out of 14 evaluate patients, as early as 3 weeks after the 2nd vaccine injection. CTLs were fully functional and killed TERT-overexpressing tumor cells. Four (29%) of 14 evaluable patients experienced stable disease for a median of 10 months. Conclusions: TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. This is the first clinical trial demonstrating that cryptic peptides are promising candidates for cancer immunotherapy. No significant financial relationships to disclose.
Predictors of self-mutilation in patients with schizophrenia
Authors: S Sweeny, K Zamecnik
Journal: American Journal of Psychiatry (1981)

The authors found that a self-imposed change in physical appearance during the acute phase before hospital admission and a previous act of self-mutilation differentiated self-mutilators from control subjects in a group of patients with schizophrenia. Anticipated object loss and living with others were factors of clinical importance but did not reach statistical significance.
A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): A report of the 2 year and median survival (MS) for the RTOG 0324 trial
Authors: G. R. Blumenschein, R. Paulus, W. J. Curran, F. Robert, F. V. Fossella, M. Werner-Wasik, P. Doescher, H. Choy, R. Komaki
Journal: Journal of Clinical Oncology (2008)

7516 Background: C225 is a chimerized monoclonal antibody that targets the epidermal growth factor receptor (EGFR). NSCLC commonly expresses the EGFR, which is associated with aggressive tumor behavior and poor clinical outcome. Preclinical model systems demonstrate radiosensitization following molecular inhibition of EGFR signaling. Methods: We report a phase II trial testing the combination of C225 with CRT in unresectable stage III NSCLC with a planned sample size of 84 PTS. Eligibility criteria included Zubrod performance status (PS) ≤ 1, weight loss ≤ 5% over past 3 months, FEV1 ≥ 1.2 L, adequate hematologic, hepatic, and renal function. PTS received an initial dose of C225 (400 mg/m2) on day 1 of wk 1, then wkly doses of C225 (250 mg/m2) until completion of therapy (wks 2 - 17). During wk 2, PTS started CRT (63 Gy/35 fractions) with wkly carboplatin (C) AUC 2 and paclitaxel (P) 45 mg/m2 x 6 doses followed by C (AUC 6) and P (200 mg/m2) x 2 cycles (wks 12–17). Interim monitoring for severe (grade ≥ 3) or excessive non-hematologic toxicities occurred after PTS had been treated and followed for at least 90 days after RT. Primary endpoints include safety and compliance of concurrent C225 and CRT. Results: 93 PTS were enrolled with 87 evaluable PTS. PTS characteristics: 57% male, median age 64 years (range 42–85), 47% PS 0, 46% stage IIIA. Median follow-up is 21.6 months (M). Response rate is 62% (n=54), MS is 22.7 M, and 24 M overall survival (OS) is 49.3%(# at risk=40). Adverse events related to treatment include 20%(n=17) of PTS with grade (G) 4 hematologic toxicities, 8% (n=7 PTS) G 3 esophagitis, and 7% (n=6 PTS) G 3–4 pneumonitis. There were 5 G 5 events. Conclusions: The combination of C225 with CRT is feasible and active with MS and OS better than any previously reported by the RTOG. These results warrant confirmation in a randomized trial. Complete compliance, toxicity, and updated survival data will be reported. Supported by RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the NCI. This abstract's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NCI. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems Incorporated Bristol-Myers Squibb, ImClone Systems Incorporated Bayer, Bristol-Myers Squibb, Eli Lilly
Do patients with MGUS require a bone marrow biopsy?
Authors: J. Singh, A. K. Malani, C. H. Huang, M. Hashmi, S. C. Mathur, C. Stasik, P. Van Veldhuizen
Journal: Journal of Clinical Oncology (2007)

8117 Monoclonal gammopathy of undetermined significance (MGUS) increase in prevalence with age and it is associated with risk of progression to plasma cell disorder. According to ASH guidelines, patients (pts) should have a complete blood count (CBC), creatinine, calcium, and a complete bone survey and periodic follow up. There has been no clear-cut guideline regarding the role of bone marrow biopsy in these patients. There is suggestion in the literature that bone marrow aspiration and biopsy is indicated if the M protein is 1.5 g/dL. Hypothesis We hypothesize that the increase in serum immunoglobulin is correlated with an increase in plasma cell in the bone marrow biopsy. Methods: We performed a retrospective chart review of 327 MGUS veteran patients seen from 2002 to 2005. Diagnostic criteria for MGUS were defined as &lt;3 g/dL serum monoclonal protein, &lt;10 % plasma cells in the bone marrow and absence of radiographic or laboratory abnormality related to the plasma cell proliferative process. Patients with smoldering myeloma were excluded. Bone marrow biopsies were available on 97/327 patients. Bone marrow biopsy with plasma cell percentage, serum protein electrophoresis (SPEP) and immunofixation (SFE), and immunoglobulin levels of these patients were retrieved and statistical analysis was performed by using Pearson correlation coefficient and linear regression analysis to detect the correlation between plasma cell percentage and immunoglobulin levels. Results: Of the 97 patients whom the bone marrow biopsy was available, 66 patients had IgG, 15 had IgA and 16 had IgM monoclonal paraprotein. There was linear correlation between serum IgG and IgA levels with the percentage of plasma cells in the bone marrow. (p&lt; 0.001 and &lt; 0.02 respectively. By regression analysis, using a cut off value of 10% plasma cells in the bone marrow, the predicted level of IgG and IgA immunoglobulin was 2124 mg /dl and 1564 mg/dl respectively. There was no correlation between IgM immunoglobulin and plasma cell percentage in the marrow. Conclusion: There is a linear correlation between serum IgG and IgA immunoglobulin with plasma cell percentage in the bone marrow. Bone marrow biopsy with plasma cell percentage of 10% or higher may be predicted in patients with MGUS with IgG or IGA above 2g/dl and 1.5g/dl respectively. No significant financial relationships to disclose.
The impact of oxaliplatin on the gonads: From bench to bedside.
Authors: Irit Ben-Aharon, Mattan Levi, Baruch Brenner, Ofer Purim, Limor Amit, Salomon M. Stemmer, Ruth Shalgi
Journal: Journal of Clinical Oncology (2015)

584 Background: Recent studies have indicated a significant increase of young colorectal cancer patients, who may then face unique survivorship issues as fertility concerns. The impact of oxaliplatin on gonadal function remains unclear. We prospectively evaluated oxaliplatin-induced gonadotoxicity in a cohort of young patients. In a preclinical setting, the impact of oxaliplatin on the gonads was prospectively studied in mice. Methods: Newly diagnosed female (&lt; 43 years) and male (&lt;45 years) patients who were candidates for oxaliplatin-based protocol were enrolled into the study. Hormonal profile (including AMH and menstrual pattern) was measured in female patients and in male patients at baseline and within 6 months post-treatment. In the pre-clinical setting, pubertal mice (female and male cohorts) were injected with oxaliplatin or saline (control) and sacrificed at various time-points (1 week, 1 or 3 months) post-treatment. Ovarian reserve was estimated by serial serum AMH. Testicular function was evaluated by serial serum inhibin and sperm count. Gonads had been retrieved at each time point for immunohistochemical study of apoptosis (TUNEL, Ki67) and repair (PCNA), ovarian reserve (AMH) and testicular reserve (DAZL). Results: Eighteen patients (10 women; 8 men) were enrolled. Median age for women was 34y (range 27-43) and for men 39y (33-44). AMH decreased in all women post-treatment, but was measurable in 8/10 patients (p&lt;0.05). FSH was elevated yet in the premenopausal range in these patients. Three patients remain menstruating during treatment. Additional five patients resumed menstruation within 6 months post-treatment. In female mice oxaliplatin induced moderate apoptosis at 1-month post treatment with a recovery of the histology compared with control mice at later time points. Inhibin was slightly decreased in men post-treatment. In male mice oxaliplatin exerted moderate apoptosis and transient decrease in spermatocyte staining in histological sections and a non-significant decrease in sperm count. Conclusions: Our results in both the clinical and pre-clinical settings indicate that oxaliplatin exerts moderate transient gonadal toxicity. Future prospective large-scale studies are warranted in order to affirm these outcomes.