tbuckley/cabot-search huggingface dataset:
Predicting positive bone marrow biopsies (BMBs) in patients (PTS) with advanced prostate cancer (APC).
Authors: David Lorente, Aurelius Gabriel Omlin, Carmel Jo Pezaro, Nina Tunariu, Roberta Ferraldeschi, Ruth Riisnaes, Joaquin Mateo, Elizabeth Sheridan, Raquel Perez Lopez, Daniel Nava Rodrigues, Mateus Crespo, Ines Figueiredo, Zafeiris Zafeirou, Amelia Altavilla, Gerhardt Attard, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2014)

180 Background: Advanced prostate cancer (APC) is a molecularly heterogeneous disease, with evidence of clonal evolution that could be responsible for resistance to treatment. About 90% of patients (pts) with APC have bone metastases. The acquisition of a bone marrow biopsies (BMBs) is a safe and feasible technique for obtaining tissue, with a low rate of complications. We hypothesized that pre-biopsy clinical variables may increase the success rate of BMBs in APC. Methods: Standard BMBs of the iliac crest were performed in APC pts between October 2011 and June 2013. All pts signed ethics approved consent. In the control cohort (n=10) BMBs were collected in pts with normal CT and bone scan appearance. Minimum, maximum, and mean Hounsfield Units (HU) of the iliac crest on pre-biopsy CTs were determined. Clinical and laboratory variables were collected from the electronic record system. Biopsies were defined as containing 50 or more or 1 to 50 malignant cells or none (negative). Univariate analysis was performed to determine variables associated with biopsy positivity with 50 or more cells. For variables with p value&lt;0.1, the optimal cut-off point was determined by ROC curve analysis. A multivariate analysis with optimal cut-off points was then performed. Results: A total of 71 BMBs were performed in 57 pts. None of the control biopsies in pts with normal CT and bone scan (10 of 10) contained tumor. A total of 46 of 61 BMBs (75.4%) were positive. 38 of 61 (62.3%) contained 50 or more cells. Prior treatments were docetaxel in 57 (79.2%) and abiraterone in 42 (58%) pts. Bisphosphonates had been used in 21 (28.8%) pts. The significant variables on univariate analysis were ALP more than or equal to 200 IU/L (p=0.059), prostate-specific antigen (PSA) more than or equal to 225 ng/mL (p=0.008), lactate dehydrogenase (LDH) more than or equal to 200 IU/L (p=0.09), mean HU more than or equal to 125 (p=0.000) and maximum HU more than or equal to 550 (p=0.001). These factors were tested in multivariate analysis. Only PSA and mean HU were significant in multivariate analysis. The combined PSA and mean HU score had an ROC AUC of 0.79. Conclusions: A combination of PSA and mean HU on CT could assist physicians in selecting APC patients/ iliac crest site more likely to have a positive BMB. Prospective evaluation is ongoing in a validation set.
Lessons learned from 110 consecutive vats lobectomies for primary, early-stage non-small cell lung cancer
Authors: B. Louie, S. Daniel, E. Wada, N. Tennent, E. Vallieres, R. Aye
Journal: Journal of Clinical Oncology (2008)

7526 Background: When surgeons adopt and integrate VATS techniques into their practices, they often mimic open surgery via smaller incisions with the goal of performing the same operation. However, the translation from open to VATS techniques may not be identical in presumed early-stage lung cancer. We hypothesized the evaluation of presumed early-stage lung cancer care would require changes to the preoperative evaluation, diagnosis and treatment. Methods: We performed a retrospective, matched case-control series comparing VATS to open lobectomy to determine if changes in evaluation and management of presumed early-stage lung cancer were warranted. All VATS lobectomies performed by a single surgical group from June 1997 to December 2005 for primary, early-stage non-small cell lung cancer were identified and matched for age, gender, tumor type and TNM status with controls. Demographic, TNM stage, histopathology, length of stay, local, regional and systemic recurrences and actuarial survival data were analyzed. Results: 110 consecutive patients underwent VATS lobectomy. There were no differences between the groups. Average LOS was 5.3 days for VATS lobectomy and 7.3 days for open controls. Mean follow-up was 38 and 36 months respectively. Overall actuarial 5 year survival rates were 53% for both groups. Stage Ia survival was 64% for VATS compared with 61% for open controls. Survival for Ib cancers was 59% and 52% respectively. Recurrence rates for VATS vs open lobectomy were: local 6% (7) vs 1% (1), regional 4% (4) vs. 2% (2) and distant recurrence rates were 12% (13) versus 22% (24). Of local recurrences, there was one port site recurrence, 3 pleural recurrences and 3 staple line recurrences due to inadvertent division of ground glass opacities and core needle biopsy. Conclusions: Changes in preoperative evaluation and surgical decision making were required to adopt and integrate VATS lobectomy into practice. VATS lobectomy can be performed safely with similar overall and stage survival. Evaluation and diagnosis of patients with deep solitary nodules, semi-solid nodules, ground glass opacities and lesions adjacent to incomplete fissues changed. We propose a new algorithm to evaluate potential early-stage lung cancer patients who are candidates for VATS lobectomy. No significant financial relationships to disclose.
Protection of adjuvant trastuzumab in sites of early relapses.
Authors: M. Campiglio, E. Tagliabue, A. Balsari, R. Bufalino, E. Ferri, L. Gianni, S. Ménard
Journal: Journal of Clinical Oncology (2011)

619 Background: About 50% of patients with HER2-positive breast tumors benefit from adjuvant trastuzumab therapy, but the highest benefit, as indicated by the HERA trial results, is restricted to the first 18 months from the start of treatment. Methods: The GHEA Italian multicentric observational study of 1021 patients treated with adjuvant trastuzumab according to HERA protocol between 2006 and 2008 registered 121 (11.8) events including distant, local, contralateral and second tumors according to anatomical sites in the first 18 months from the start of treatment (early relapses) and thereafter (late relapses). Based on an expected 50% reduction of early metastases at any site, the number of metastases per site was calculated and compared with the observed data to yield a percent trastuzumab protection value at each single site. Results: Early relapses comprised 49 (4.8%) events and late relapses represented 72 (7%) events. The frequency of late metastases in the different sites was similar to that observed for HER2-positive tumors before the trastuzumab era, while the frequency of early relapses followed a different pattern, i.e., liver, lung and lymph node relapses were less frequent in early than in late relapses (10.5% vs 18.6%, 10.5% vs 23.2% and 2.6% vs 9.3%, respectively), while bone and CNS metastatic disease was more frequent in early than in late relapses (36.9% vs 18.6% and 23.7% vs 14%, respectively). No changes in frequency of multiple metastases was observed (15.8% vs 16.3%). Trastuzumab did not protect against bone and CNS metastases (0% and 10% respectively), whereas a protection of 71.4% for liver, 75% for lung, 85.6% for lymph nodes was observed. Conclusions: In addition to the well-known CNS relapses due to the failure of the antibody to pass the blood-brain barrier, also bone relapses were found to be resistant. This may be due to a bone microenvironment inadequate for antibody activity or escape of bone metastases from HER2 targeting. Excluding the two “resistant” sites, the protection by trastuzumab was more than 70% in all other distant metastases. Supported by AIRC and Roche.
Ductal lavage cytology in patients with ductal carcinoma in situ (DCIS).
Authors: Andrea Behr, Edi Brogi, Alexandra S. Heerdt, Kimberly J. Van Zee, Leslie L. Montgomery
Journal: Journal of Clinical Oncology (2013)

89 Background: Ductal lavage (DL) is a procedure used to obtain epithelial cells from a breast duct for cytologic evaluation. Previous studies have investigated DL as a potential screening procedure for women at high-risk for cancer. The data, however, does not support a significant correlation between lavage cytology and the presence of invasive carcinoma. It is postulated that an invasive cancer causes destruction of the involved ducts which prevents direct sampling of the malignant intraductal cells. Because ductal carcinoma in-situ (DCIS) does not disrupt the breast ductal structure, DL may yield a more representative cytologic sample in patients with DCIS. Methods: Ductal lavage was performed in the affected breast of 32 women undergoing mastectomy with preoperative diagnosis of DCIS. The lavage procedure was done in the operating room after induction of general anesthesia by cannulating a duct yielding fluid on the nipple and instilling saline which was then aspirated and sent for cytologic evaluation. A cytopathologist classified each sample as insufficient cellular quantity, benign, mild atypia, marked atypia, or malignant. Results: A successful lavage was obtained from 22 (69%) of 32 women undergoing DL in the operating room. Of these 22 cytology samples; 4(18%) had an insufficient cellular quantity, 4 (18%) had mild atypia, 6 (27%) had marked atypia, and 8 (36%) had malignant cells. Twenty one of these 22 women had DCIS in the surgical mastectomy specimen. Seven (32%) patients were found to have invasive ductal cancer in addition to DCIS on final pathology. Conclusions: Our results show that DL reveals markedly atypical or malignant cytology in 64% of patients with DCIS who underwent a successful lavage procedure. As an office procedure, DL may have the ability to obtain viable ductal carcinoma cells repeatedly over time in the same patient. Thus, DL may have an important role in patients with DCIS who are involved in window trial studies investigating response to medical treatments prior to surgical intervention. Further studies to evaluate the reproducibility of the ductal lavage results in patients with DCIS are needed to confirm these findings.
Beta-2-Microglobulin Is An Independent Predictor of Progression in Asymptomatic Multiple Myeloma.
Authors: Davide Rossi, Marco Fangazio, Lorenzo De Paoli, Valeria Pinto, Paola Riccomagno, Alessia Puma, Antonio Ramponi, Guido Monga, Gianluca Gaidano
Journal: Blood (2009)
InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease.
Authors: Francesco Sclafani, Richard A. Adams, Cathy Eng, Al Bowen Benson, Robert Glynne-Jones, David Sebag-Montefiore, Dirk Arnold, Amitesh Chandra Roy, Marianne Grønlie Guren, Eva Segelov, Matthew T. Seymour, Annette Bryant, Clare Peckitt, David Cunningham, John A. Bridgewater, Jack Welch, Peter J. O'Dwyer, Elisabeth Dupont, Andrea McConnell, Sheela Rao
Journal: Journal of Clinical Oncology (2015)

TPS792 Background: Metastatic squamous cell carcinoma of the anus (SCCA) is a rare condition with 5-year overall survival (OS) rate of 32%. CDDP/5-FU is commonly used in the first-line treatment of patients with ILR or metastatic disease. This practice is based on retrospective series and data from randomised trials are lacking. Recent retrospective studies showed promising activity of CBDCA/PTX in this setting. Methods: InterAACT is an international, multicentre, open label, randomised phase II trial comparing two chemotherapy regimens in patients with ILR or metastatic SCCA. Eligible patients are randomised in a 1:1 ratio to CDDP (60 mg/mq, D1q21) plus 5-FU (1000 mg/mq/24h, D1-4q21) or CBDCA (AUC 5, D1q28) plus PTX (80 mg/mq, D1,8,15q28). Stratification factors are: performance status, extent of disease, HIV status and country. The primary endpoint is response rate (RR). Secondary endpoints include progression-free survival, OS, toxicity and quality of life. Based on a RR estimate of 40% in the CDDP/5-FU arm 80 patients are to be recruited to detect 10% difference in RR between the two arms with 80% power (phase II selection trial design). Correlative biomarker analyses are planned in tumour tissue and blood samples. The trial is sponsored by The Royal Marsden NHS Foundation Trust and endorsed by the International Rare Cancer Initiative (IRCI) group. Approximately 50 centres in the UK, Europe (EORTC), Scandinavia, US (ECOG-ACRIN) and Australia (AGITG) are estimated to participate and recruitment is anticipated to be completed within 3 years. Recruitment started in December 2013. As of September 16, 2014, 6 sites in the UK are open to recruitment and 6 patients have been randomised (3 to CDDP/5-FU and 3 to CBDCA/PTX). InterAACT aims to provide the first randomised evidence for the treatment of ILR and metastatic SCCA, to identify the optimal chemotherapy backbone to combine with targeted agents in future studies and to confirm the feasibility of conducting an international multicentre trial for this rare tumour. Clinical trial information: NCT02051868.
Improving radiotherapy utilization rates in Ontario.
Authors: Michelle Ang, Eric Gutierrez, Nicoda Foster, Lisa Favell, Padraig Richard Warde
Journal: Journal of Clinical Oncology (2014)

48 Background: Radiotherapy (RT) utilization is the proportion of patients (Pts) with a new diagnosis of carcinoma that receives at least one course of RT during the duration of their illness (MacKillop et al). In Ontario, the benchmark for utilization is 42%, and the target rate for Cancer Care Ontario (CCO) is 48%. However in 2005/06 Ontario’s utilization rate was only 35%. This shortfall implies that a significant number of Pts in Ontario were not receiving the best possible treatment. Methods: CCO has developed Capital Investments Strategies to take into account a growing population, an increased incidence of cancer (2.7% per annum), and changing demographics. The most recent (2012) has developed a plan for a gradual improvement in utilization at a rate of 0.5% per annum. With support from the Ministry of Health and Long-Term Care (MOHLTC), the amount of RT Units (RTUs) available increased from 77 (2005/06) to 103 (2013/14). In addition, the MOHLTC supported training programs for provincial Medical Physicists and Radiation Therapists to ensure effective staffing for increased RTUs. Results: Due to investments in RTUs and training, the number of Pts treated in Ontario has risen over 38% from 26,448 in 2005/06 to 36,613 in 2012/13. As a result, provincial utilization rates have risen from 35.1% in 2004/05 to 38.8% in 2012/13, closer to provincial targets. Notable improvements have been seen in centres such as The Carlo Fidani Peel Regional Cancer Centre, where the total number of RT Pts treated increased from 623 (2005/06) to 2532 (2012/13). Similar improvements are seen in other Local Health Integration Networks where comparable investments have been made. These improvements have been attained at the same time as provincial RT wait times have significantly improved from 80.2% (Jan 2010) to 91.6% (Dec 2012) of Pts seen within targets, exceeding provincial targets of 87%. Conclusions: The increase in RT utilization rates provincially demonstrates the success of developing a comprehensive capital investment strategy and coupling it with increased investments in human resource planning. The increased utilization rate has outpaced the increasing cancer incidence and demonstrates the success of these strategies, providing better access to care for cancer Pts in Ontario.
Preoperative chemoradiotherapy for pancreatic cancer encountered vertebral compression fractures.
Authors: Keisuke Otani, Teruki Teshima, Kinji Nishiyama, Yuri Ito, Yoshifumi Kawaguchi, Koji Konishi, Hidenori Takahashi, Hiroaki Ohigashi, Nobuhito Araki, Osamu Ishikawa, Kazuya Oshima
Journal: Journal of Clinical Oncology (2013)

227 Background: Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer at our institute achieved excellent cure rates, while treated patients encountered vertebral compression fractures (VCFs) frequently. Methods: From January 2006 to December 2011, 220 patients (male/female: 134/86, median age: 66 (range: 33-84)) with resectable pancreatic cancer have been treated with preoperative CRT with GEM. This method consisted of concurrent radiotherapy (50-60 Gy in 25 fractions over 5 weeks) and chemotherapy (GEM 1,000 mg/m 2 intravenous, weekly for 12-15 weeks, 3 times during 4 weeks). Three-dimensional conformal radiotherapy was used and its fields covered both primary pancreatic tumor and retropancreatic tissues with 50 Gy level. Boost irradiation to the roots of celiac and superior mesenteric arteries with 2.4 Gy/fr using field-within-field technique has been started since 2009. The risk factors for VCF and its causes were retrospectively analyzed for 1,308 Th10-L3 vertebral bodies. Results: Follow-up time from the initiation of CRT ranged from 3.4-73.9 months (median: 17.9). Median overall survival time of these patients was 40.6 months. Radical surgery was completed in 164 patients (75%). Twenty-five patients (11%) diagnosed as VCF (CTCAE v4.0 grade1/2: 12/13) and 22 of them were at 3.6-23 months from CRT. Cumulative incidence rates at 2 years were 18.9% in total, 8.5% in male and 38.4% in female (p = 0.0002). Corresponding rates were 5.1% in age &lt; 60 and 24.9% in age ≥ 60 (p = 0.0107). On their courses 37 de novo VCFs (Th10/11/12/L1/2/3: 2/3/11/13/7/1) were observed at first and 9 patients repeated VCFs near the initial VCFs. Dose-volume factors of each vertebral bodies also significantly correlated with VCF; vertebrae whose mean dose were &lt; 38 Gy/ ≥ 38 Gy developed VCFs in 2.7%/10.0% at 2 years (p &lt; 0.0001), vertebrae whose V 30 were &lt; 80%/≥80% developed VCFs in 2.4%/10.6% (p &lt; 0.0001). Conclusions: Besides women and higher age, dose-volume factors of radiotherapy were risk of developing VCF in patients with pancreatic cancer after preoperative CRT with GEM. These findings should be considered to avoid VCFs as late adverse event after CRT for pancreatic cancer, especially in IMRT era.
Phase I clinical trial of cancer vaccine with five novel epitope peptides for patients with metastatic colorectal cancer (mCRC).
Authors: S. Hazama, M. Oka, K. Yoshida, T. Tsunoda, S. Yoshino, Y. Hinoda, Y. Nakamura
Journal: Journal of Clinical Oncology (2011)

2510 Background: A phase I clinical trial was conducted for patients (pts) with mCRC using 5 novel HLA-A24-restricted peptides, which were derived from 3 oncoantigens (RNF43, TOMM34, KOC1), and from VEGFR1 and VEGFR2. Methods: This study was conducted to evaluate the safety and to find the recommended dose (RD) of the combination of 5 peptides, and secondary to evaluate immunological and antitumor effects. Eighteen HLA- A2402- positive mCRC pts who failed to standard therapy were enrolled in this study with written informed consents. Each of the 5 peptides was subcutaneously injected with 0.5 mL of incomplete Freund's adjuvant (IFA) to the inguinal or axillal regions in 5 separate regions weekly for 4 weeks in a dose-escalation manner (doses of 0.5, 1, and 3 mg each peptide/ body, 3 pts cohort). In the next step, the safety was confirmed by adding 3 pts on the RD dose. Moreover, "the cocktail of 5 peptides" at RD with 1.5 mL IFA was injected for other 6 pts to 3 separate regions. Vaccinations were continuing until the patients' refusal. ELISPOT assay was performed before and after vaccinations every 4 weeks. Results: The vaccination was well tolerated without any treatment associated adverse events of grade 2 or higher. The total numbers of peptides induced antigen specific response were 2 peptides in 3 pts at 0.5mg, 6 in 3 pts at 1.0 mg, and 18 in 6pts at 3.0 mg, respectively. We therefore decided that the RD was 3.0 mg / body. In 6 pts injected "peptides cocktail", the numbers of peptides induced antigen specific response were 19, which indicated that the injection of "peptides cocktail" had same immunogenicity as separated injections. One patient experienced a CR in lymph nodes metastasis lasting 3 years and 6 pts revealed SD for 4 to 7 months (disease control rate= 7/18 (39%)).The median overall survival time was 15.2 months, and 2 years survival rate was 46 %. Pts with 3 or more peptides specific responses (n=10) survived longer than other pts significantly (p=0.027). Conclusions: This cancer vaccine therapy using five different peptides was safety and useful for mCRC and therefore warrants further clinical studies.
A phase II trial of CPT-11 in patients (pts) with advanced gastric or gastroesophageal (GE) junction adenocarcinoma (ADCA): A clinical and pharmacodynamic evaluation. A North Central Cancer Treatment Group (NCCTG) Study
Authors: C. Erlichman, R. M. Goldberg, M. R. Mahoney, B. F. Kabat, J. L. Huntington, D. J. Sargent, T. J. Sebo, S. H. Kaufmann, J. R. Egner, H. C. Pitot
Journal: Journal of Clinical Oncology (2005)

4026 Background: The goals of this study were to determine the response rate (RR) and toxicity of CPT-11 as first-line therapy for gastric and GE junction ADCA, to describe the overall survival (OS) and time to progression (TTP), and to evaluate molecular markers as predictors of RR. Methods: CPT-11 (320 mg/m2 IV) was given to 11 pts q3 weeks but was reduced to 290 mg/m2 and then to 260 mg/m2, due to toxicity (JR Egner, et al. Proc Am Soc Clin Oncol, 18:282A, 1999). Pre-treatment tumor tissue was analyzed for DNA ploidy; and MIB-1, Bcl-2, p53, Bcl-xl, and Topoisomerase-I (TOPO) by immunohistochemistry. Ploidy, MIB-I, p53, and TOPO were quantified (% nuclear area) by digital image analysis (Sebo, et al. Am J Surg Pathol, 26(4):431–439, 2002). Results: Of 68 eligible patients entered on trial, 59 had pretreatment biopsies. A mean of 5 courses were administered (range 1–24). Grade 3+ toxicities included (% patients): neutropenia (41%), leukopenia (34%), diarrhea (21%), nausea (18%), vomiting (16%), lethargy (9%), and abdominal pain (7%). 13 confirmed responses (5 PR, 8 regressions) were observed (19%, 95% CI:12–33), with a median duration of 6 months (mos) (95% CI:4–8). Median TTP and OS were 3 mos (95% CI: 2–4) and 6 mos (95% CI:4–9). Pre-treatment biopsies revealed that 88.9% were nondiploid, 96.5% had weak or no staining for Bcl-2 and 83.9% had moderate to strong staining for Bcl-xl. MIB-1 and TOPO were positively correlated (rho=0.43, p<0.01). Only MIB-1 was significantly associated with RR (mean expression of 33.7% for responders versus 19.8% for nonresponders p<0.01). Conclusions: CPT-11 alone in patients with gastric or GE junction ADCA showed modest activity. MIB-1 is a predictor for RR to CPT-11. Other biomarkers failed to demonstrate any association with outcome. (Supported in part by CA25224, CA73709, and Pharmacia & Upjohn) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Genentech, Lilly Oncology, Pfizer, Sanofi Pfizer, Sanofi Pfizer, Sanofi Sanofi