tbuckley/cabot-search huggingface dataset:
Curative treatment for patients with synchronous liver metastases and peritoneal carcinomatosis of advanced colorectal cancer (aCRC): A multicenter study of the French Association of Surgery.
Authors: Rea lo Dico, Etienne Gayat, Olivier Glehen, Diane Goéré, Clarisse Eveno, Francois Quenet, Marc Pocard, Thierry André
Journal: Journal of Clinical Oncology (2016)

3558 Background: Patients with synchronous peritoneal carcinomatosis (PC) and liver metastasis (LM) of colorectal cancer (CRC) are generally considered for exclusive systemic palliative chemotherapy. Aggressive surgical approaches combining hepatectomy and peritoneal resection with curative intent remain controversial in such a setting and based on no solid data. The aim of this prospective cohort was to assess morbidity, mortality, disease-free survival (DFS) and overall survival (OS) of patients with PC and LM of aCRC origin treated with an aggressive therapeutic approach combining surgical treatment of liver and peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: All patients with PC and synchronous LM who undergone cytoreductive surgery and LM resection in the same time followed by HIPEC were registered in the prospective database of the French Association of Surgery and analysed. The primary endpoint was survival from the time of surgery. Results: From 1993 to 2015, 146 patients were analyzed. After a mean follow-up of 36 months, the median OS and DFS, were respectively 27,2 and 9.5 months. The median number of LM was 4 (range, 1–8).Postoperative morbidity Grade III - IV (Dindo Classification) rate was 14.8% with no postoperative death reported. Patients with complete cytoreductive surgery (n = 132) had higher OS than those with incomplete cytoreduction (n = 14) with a median of 29, versus 4 months respectively (p = 0.0001). Rectal primary tumor, PCI of 13 or more, positive nodal status of the primitive tumor, and more than 3 LM were not identified as independent factors for poor OS. Conclusions: This multicenter study is the largest series currently reported confirming that prolonged survival can be achieved in selected patients suitable for PC and LM surgery. Multimodality treatment, including surgical treatment of PC and LM with curative intent, and heated intraperitoneal chemotherapy had acceptable in terms of morbidity and allows prolonged survival.
P03.04 Observational, prospective study on complications and tolerability of PICC (central venous catheter with peripheral insertion) in neurooncological patients
Authors: G Simonetti, A Sommariva, C Basso Ricci, E Anghileri, A Botturi, M Eoli, P Gaviani, E Lamperti, C Moreschi, A Silvani
Journal: Neuro-Oncology (2018)

The use of central venous catheter with peripheral insertion (PICC) has increased rapidly in recent years particularly in cancer patients. However, the benefit provided may occasionally be affected by relevant complications. The precise incidence and risk of PICC related complications is unknown, as well as patients tolerability. The study aims to collect immediate, early and late complications related to PICC in neuro-oncological patients as well as evaluate the tolerability through semi-structured interviews. Neuro-oncological patients at IRCCS Neurologico C. Besta, with PICC placed for normal clinical practice were consecutively included in the study. PICC related complications were recorded immediately (during the procedure), early (after 24 hours and within one week from placement) and late (after one week from placement and until the removal). All patients were also evaluated for tolerability through semi-structured interviews conducted after a week, 1 month, 3 months and 5 months from PICC placement. 30 neurooncological patients have been enrolled. Chemotherapy regimens administered by the PICC were: fotemustine (73.3%), HDTMX (13.3%), bevacizumab (6.6%), PCV (6.6%). One week after PICC placement, 13.3% of patients presented hematoma (grade 1 CTCAE); 30% of the patients did not feel pain during the positioning procedure, in the remaining patients the average level of perceived pain was 2 (range 2–6), on a scale from 0 to 10. Regarding complications, 10% of patients showed the presence of semi-occludent /occluding thrombus as well as the presence of fibrin flaps. Only one infectious occurred (staphylococcal sepsis, grade 4 CTCAE). All events required removal of the device. In 6.6% of cases a dislocation of the PICC was recorded. One week after device placement, 94% of patients perceived the experience as “overall positive”. Within one month, 78.5% of patients did not consider the device as a “foreign body”. In 85.7% of cases, the PICC seems to give greater security during chemotherapy administration. In 57.1% of the cases PICC did not affect the habits related to hygiene or clothing (85.7%). In all cases, there were no difficulties while sleeping. The data obtained from the study will allow to implement corrective actions in order to reduce specific complications. Regarding tolerability, the device seems to be positively accepted in the majority of interviewed patients, without affecting the activities of daily life.
Dynamically trace the prognosis of patients with hepatocellular carcinoma through constructing survival paths with time-series data.
Authors: Lujun Shen, Wang Li, Chen Chen, Feng Shi, Peihong Wu
Journal: Journal of Clinical Oncology (2017)

e15636 Background: Hepatocellular carcinoma (HCC) is featured by high risk of local recurrence and intrahepatic metastasis, and always requires repeated treatment. A novel prognostic system maximally utilizes time-series data and facilitates dynamic prognosis prediction is warranted. Methods: 1341 BCLC stage B HCC patients received treatment at Sun Yat-sen University Cancer Center from Jan, 2007 to Dec, 2012 were enrolled (979 pts for derivation, 362 pts for validation). Time-series data on serum tumor markers, biochemical and hematological index, medical imaging and associated changes (CT and/or MRI) were collected. Every 3 months represented an individual time point and a total of 9 time points were defined (Table 1); data in each time interval were allocated to associated time point. To construct the survival path, the derivation cohort was sequentially divided into subgroups by one selected feature in each time point; the feature selection criteria were: 1. independent prognostic factor in Cox model; 2. most impactful based on the change of -2Log likelihood after elimination from the model. The survival path of HCC patients was further visualized and its predictive value at each time point was compared with BCLC staging system. Results: Based on the time-series data of derivation cohort, we divided the population into 13 different paths with distinct response of treatment. The survival path system showed superior prognostic value than BCLC staging system at all time points except for the no.2 time point (Table). The validation cohort showed consistent finding. Conclusions: The methodology of survival path was valuable in dynamically tracing the prognosis of HCC patients and could further facilitate treatment planning. The visualization of data by survival path could be a new tool in processing the big data of cancer in the future. [Table: see text]
Solitary fibrous tumour relapsing with a single bone metastasis: Report of five cases.
Authors: Vittoria Colia, Salvatore Provenzano, Carlo Morosi, Paola Collini, Gianpaolo Dagrada, Angelo Paolo Dei Tos, Andrea Marrari, Paolo Giovanni Casali, Silvia Stacchiotti
Journal: Journal of Clinical Oncology (2016)

e22525 Background: Solitary fibrous tumour (SFT) is a rare soft tissue sarcoma with a low metastatic potential (10-15%). A higher metastatic rate (40%) is observed in the high-grade/dedifferentiated variant. As for other STS, the most common expected site of distant spread are the lungs, followed by the liver. Bone involvement is generally viewed as a late stage of disease spread. We report on a retrospective series of SFT patients (pts) who suffered from a single distant bone recurrence as their first metastatic event, without evidence of any other organ involvement. Methods: All pts affected by bone metastasis from SFT as their first distant event, without any evidence of other site(s) of metastasis, observed at our Institution between October 2009 and October 2015, were considered. Bone involvement from SFT was pathologically assessed in all cases and confirmed by expert pathologists, who also compared the metastatic tissue with the primary tumor. Disease status was assessed in all pts by whole body computed tomography scan (CT), including brain, MRI and/or CT of the primary tumour site, bone scan. Results: A total of 5 pts were retrospectively identified. Primary tumour arose from the meninges in 4 pts, from soft tissues of the left thigh in one. Bone metastases were located to the vertebrae, the hip and the rib. In all cases, bone relapse was the first event, with one pt also having a local relapse. Median time from the primary tumor and the evidence of bone relapse was 53 months (range 20-60). In 3/5 pts RT was given, surgery in one, surgery and RT in one. At a median follow-up of 59 months (range 31-79), all pts are alive: 2/5 without disease, 1/5 with metastatic disease (lungs) and 2/5 with a single bone metastasis. Conclusions: This small series in a relatively rare histology suggests that isolated, possibly late, bone metastases are a plausible scenario, in particular in meningeal SFT. Notably, new bone lesions in a pt with a history of SFT should be always investigated. Exclusive local treatments may be an option, though collection of such series would be needed to define the best treatment strategy.
The clinical experience: Hereditary cancer testing by a 25-gene panel.
Authors: Elias Obeid, Andrea Forman, Michael J. Hall, Veda N. Giri, Susan Montgomery, Kim Rainey, Christina Rybak, Kelsey Moyes, Jennifer Saam, Mary Beryl Daly
Journal: Journal of Clinical Oncology (2014)

1548 Background: Prior to next generation sequencing (NGS) technology, genetic testing for hereditary cancer risk was gene and syndrome-specific. Fox Chase Cancer Center began offering patients a 25-gene panel, utilizing NGS, through a commercial early access clinical program in September of 2013. This panel includes BRCA1/2 and other high/moderate risk genes for breast, colon, and other cancers. The utilization of this panel test compared to syndrome-specific testing has not been assessed in a clinical setting. Here we describe our clinical experience with this new testing option. Methods: Patients were offered a choice between syndrome-specific testing and a 25-gene panel from Myriad Genetics Laboratories. Of 152 tests ordered from September 4, 2013 to January 24, 2014, results were available for 144 patients. All tested patients met NCCN criteria for genetic testing or were deemed appropriate for testing after assessment by a certified genetic counselor. Results: Of 144 test results available, 87 had 25-gene panel testing, 26 had syndrome-specific testing for BRCA1/2, and 31 had targeted testing (Ashkenazi panel, single site, or deletion/duplication analysis). In the BRCA1/2 test group, a deleterious mutation was seen in 3/26. Of note, 12/26 patients declined the 25-gene panel. From 87 patients in the 25-gene panel, 8 had clinically positive results for a deleterious gene mutation of which 3 (3/8, 37.5%) were unanticipated test results that influenced clinical management (mutations in ATM, APC, and RAD51D). All 8 individuals were affected with cancer. We found a high rate of variants of unknown significance (VUS) (29/87, 33.3%), as well as a high rate of monoallelic deleterious mutations in MYH (5/87, 5.7%). Conclusions: Multigene panel testing is now available for patients seeking genetic identification of an inherited predisposition to cancer. Our experience indicates that such a multigene panel may yield results that would not otherwise be discovered through syndrome-specific testing, and may provide additional clinical guidance. However, results can have uncertain clinical impact given the high VUS rate as well as other findings, such as monoallelic MYH, for which there is no clear medical management at the present time.
A phase I/II trial of TG01/GM-CSF and gemcitabine as adjuvant therapy for treating patients with resected RAS-mutant adenocarcinoma of the pancreas.
Authors: Daniel H. Palmer, Svein Dueland, Juan W. Valle, Anne-Kirsti Aksnes
Journal: Journal of Clinical Oncology (2017)

4119 Background: TG01 (a mixture of 7 RAS peptides) is an injectable antigen-specific cancer immunotherapy targeted to treat patients (Pts) with KRAS mutations, found in more than 85% of pancreatic adenocarcinomas. There is scope for improvement in adjuvant treatment of resected pancreatic cancer; with 1- and 2-year published overall survival (OS) rates ranging from 56-80% and 30-54% respectively. TG01 induces RAS mutant-specific T-cell responses which are enhanced by co-administration of GM-CSF. This study evaluates safety, immunological response and OS of TG01-immunotherapy with adjuvant gemcitabine chemotherapy. Methods: Pts were eligible after an R0 or R1 pancreatic adenocarcinoma resection. As soon as possible after surgery, TG01 (0.7 mg intradermal injection (id)) together with GM-CSF (0.03 mg id) was given on days 1, 3, 5, 8, 15, 22 and 2-weekly thereafter until the end of gemcitabine (starting within 12 weeks of surgery and given for 6 cycles). Thereafter TG01/GM-CFS were given 4-weekly up to 1 yr and 12-weekly up to 2 yrs. Immune response was assessed using antigen-specific (TG01) Delayed-Type Hypersensitivity (DTH) and T-cell proliferation. OS was assessed from surgery; ~8 weeks before first TG01 injection. Results: To date, 19 pts (68% R1) from 3 sites (Norway and UK) and have been followed for 2 yrs.Eight SARs in 5 pts have occurred; 4 related to gemcitabine (anemia, pulmonary infection and 2 fever); 3 related to TG01/GM-CSF (2 anaphylaxes and 1 hypersensitivity); and 1 possibly related to all products (dyspnea). The allergic reactions only occurred after several cycles of gemcitabine and resolved within 1-2 hrs. There was no treatment related deaths.16/19 (84%) pts had a positive DTH by week 11. Proliferation of mutant RAS specific T-cells is being analyzed. OS rate at 1 and 2 yrs were 89.5% (95% CI 75.7, 100.0) and 68.4 (95% CI 47.5, 89.3), respectively. Median OS was 33.1 months (95% CI 16.8, 40.1). Conclusions: TG01/GM-CSF generated early immune responses in 84% of patients with R0/R1 resected pancreatic cancer. The regimen was generally well tolerated although some late, manageable allergic reactions were seen. OS was encouraging in view of published reports. Clinical trial information: NCT02261714.
Regression of epithelial cancers in humans following t-cell receptor gene therapy targeting human papillomavirus-16 E7.
Authors: Nisha Nagarsheth, Scott Norberg, Stacey L. Doran, Jennifer Ann Kanakry, Sabina Adhikary, Colleen Schweitzer, Stephanie H. Astrow, William C Faquin, Nikolaos Gkitsas, Steven Highfill, David Stroncek, Christian Hinrichs
Journal: Journal of Clinical Oncology (2018)

3043 Background: Adoptive T-cell therapy with gene-engineered T cells is an emerging cancer treatment strategy. Study of this approach in epithelial cancers, the most common types of malignancies, has been limited. We initiated a clinical trial of gene-engineered T cells that target human papillomavirus (HPV)-16-E7 for the treatment of patients with metastatic HPV-16+ cancers. Methods: The clinical trial was designed as a phase I study with three dose levels (DL) of gene-engineered T cells (DL1: 1 x 109, DL2: 1 x 1010, DL3: 1 x 1011). Patients had metastatic HPV-16+ cancers from any primary tumor site. Patients received a single infusion of autologous T cells that were gene-engineered to express an HLA-A*02:01-restricted T-cell receptor that targets HPV-16 E7 (E7 T cells). A lymphocyte-depleting conditioning regimen was administered before treatment. E7 T cell infusion was followed by high-dose systemic aldesleukin. We report the early results of the ongoing study. Results: Eight patients were treated. No dose-limiting toxicity, off-target T-cell toxicity, or cytokine-release syndrome occurred. Objective clinical responses were observed in 3/7 evaluable patients. Responses occurred in patients with vulvar, oropharyngeal, and anal cancer. Two of these patients had been previously treated with anti-PD-1 checkpoint blockade. One response occurred at DL1. The patient had extensive metastatic vulvar cancer involving the lungs, retroperitoneum, pelvis, and thigh. She had been previously treated with seven systemic anti-cancer agents. The response lasted 8 months after treatment. Two responses occurred at DL2. One was in a patient with metastatic anal cancer with lung, pleura, and kidney tumors. The response is ongoing after 7 months. In the initial six patients, the E7 TCR was expressed by 90-99% of the infused T cells, and E7 T cells were detectable in the peripheral blood six weeks following treatment (1% to 4% at DL1, 5% to 45% at DL2). Conclusions: Tumor regression can occur following treatment of an epithelial cancer with gene-engineered T cells. These findings support continued study of E7 T cells and possibly other types of gene-engineered T cells in epithelial cancers. Clinical trial information: NCI-16-C-0154.
A phase II study of neodjuvant chemoimmunotherapy followed by stereotactic radiotherapy/nelfinavir in patients with locally advanced CA125 expressing pancreatic adenocarcinoma.
Authors: Chi Lin, Quan P. Ly, Lyudmyla Derby Berim, James K. Schwarz, Madi Madiyalakan, Christopher F. Nicodemus, Michael A. Hollingsworth, Jane L Meza, Chandrakanth Are, James Padussis, Jean L. Grem
Journal: Journal of Clinical Oncology (2018)

e16202 Background: CA-125, a tumor marker expressed in > 50% pancreatic adenocarcinoma (PAC), was targeted with oregovomab (O), a monoclonal antibody currently in development as chemoimmunotherapy (CIT) for ovarian cancer. The objectives of this trial were to evaluate the safety, activity, & induction of cellular immune response of neoadjuvant & adjuvant CIT & stereotactic radiotherapy (SBRT) with nelfinavir (NFV) in patients with locally advanced PAC. Methods: CIT consisted of 7 3-week cycles of gemcitabine (GEM) 750 mg/m² (females) or 900 mg/m² (males), leucovorin (LV) 50 mg/m², Fluorouracil (FU) 2700 mg/m²/24 h on days 1 & 8, & O (2 mg) on day 15 (If CA125 ≥ 10). SBRT 40 Gy in 5 fractions with NFV (1250 mg BID) was given after 3 cycles of CIT. Surgery was performed after 4 cycles of CIT for resectable disease. Three more cycles of CIT were given adjuvantly or post-SBRT for unresectable disease. Results: The trial was closed prematurely due to the replacement of GEM/LV/FU by FOLFIRINOX & GEM/abraxane as standard of care for PAC. Eleven patients (2 females) were enrolled; 9/11 had O (1 had CA125 < 10, 1 died unexpectedly on day 2 of study); 10 got SBRT; 4 had a resection; 5 had 7 cycles of CIT (4 neoadjuvant & 3 adjuvant); 6/11 had ≥ grade 3 drug-related adverse events (AEs) using CTCAE v3. The most common AEs were marrow toxicity (low ANC 91%, low WBC 82%, low lymphocyte 45%, low platelet 36%, anemia 27%), liver function abnormalities (27%) and acidosis (18%). Median follow up was 17 months (M); 7 had disease progression (liver, 5, peritoneum, 1, retroperitoneal, 1); median time to progression 6.9 M (4-12); median survival 13 M (7-31); & 2 year survival 28%. Among those who got 7 cycles of CIT & SBRT, 2 developed CA125-specific interferon-gamma+ CD8 T cells, as detected by enzyme-linked immunoSpot, and survived 28+ & 31M. Conclusions: Antibody-based targeting of patient-specific CA125 in the context of CIT induced specific CD8 T-cell (Interferon-γ+) immunity in select PAC patients. CIT SBRT is a feasible approach to induce immune responses to patient specific neo-antigen; however, activity should be reassessed using current frontline chemotherapy regimens. Clinical trial information: NCT01959672.
Clinical outcomes in borderline resectable pancreatic cancer (BRPC): A single institutional analysis.
Authors: Daniel Ezekwudo, Bolanle Gbadamosi, John Khoury, Leann Blankenship, Susanna S. Gaikazian, Joseph M Anderson, Michael J. Stender, Robert P Jury, Laura Nadeau, Cotant Matthew, John M. Robertson, Jeffrey H. Margolis, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2018)

e16232 Background: Neoadjuvant therapy in BRPC serve to improve margin negative resection rate, however emerging data indicate otherwise. Aim of the study is to retrospectively investigate the clinical outcomes of BRPC patients treated with neoadjuvant therapy at our Institution. Methods: Out of 94 patients screened, 53 patients met National Comprehensive Cancer Network (NCCN) diagnostic criteria for BRPC from January 2007 to January 2017. Type of neoadjuvant therapy and surgery, disease-free survival (DFS) and overall survival (OS) were examined. Statistics were performed using SAS System for Windows version 9.3. Results: Of 53 patients, 54.7% received neoadjuvant therapy with majority receiving Gemcitabine based regimen followed by FOLFIRINOX (table 1). 24.1% received chemotherapy + Radiation. Among those who received neoadjuvant therapy, 48.3% had progressive disease (PD) radiologically and the rest had either partial (PR) or stable response (SD). Type of neoadjuvant therapy did not affect radiological response (p = 0.41). 97% received at least 4 cycles of neoadjuvant chemotherapy. Only 31.03% of patients had R0 resection whereas 75.9% have less than R0 resection. Pancreatectomy with R0 resection resulted in a statistically significant median DFS of 21.3 months (95% confidence interval (CI) 12.3-39.1), and median OS of 18.2 months (95% CI, 14.2-22.6) versus a median DFS of 6 months and median OS of 3 months among patients without R0 resection. Conclusions: DFS and OS benefits were affected by the type of surgery not neoadjuvant therapy. Although a single institutional analysis, it conforms to recent reports on clinical outcome of BRPC. Further study is necessary to elucidate their clinical pathway. Table 1: Outcome Characteristics Follow up duration (years) 10 P value Neoadjuvant therapy: P = 0.41 Gemcitabine-based 17/29 (58.6%) FOLFIRINOX 11/29 (38%) Carboplatin + etoposide 1/29 (3.4%) Chemotherapy + Radiation 7/29 (24.1%) Radiographic Response: PR 11/29 (38% SD 4/29 (14%) PD 14/29 (48.3% Type of Surgery (Pancreatectomy): P < 0.001 R0 resection 9/29 (31%) < R0 resection 20/29 (69%) Disease Recurrence: Yes 19/29 (65.5%) No 10/29 (34.5%) Vital status: Alive 11/29 (37.9%) Dead 18/29 (62.1%)