tbuckley/cabot-search huggingface dataset:
Does combined dose intensification radiotherapy improve disease control in resectable retroperitoneal sarcoma? Long-term results of a phase I/II trial.
Authors: Myles JF Smith, Paul F Ridgway, Charles N Catton, Amanda Cannell, Brian O'Sullivan, Lynn A Mikula, Julia J Jones, Carol Jane Swallow
Journal: Journal of Clinical Oncology (2012)

10050 Background: Late failure is a challenging problem in retroperitoneal sarcoma (RPS) and reported 10 yr overall survival (OS) rates range from 20-30%. Use of preoperative external beam radiotherapy (XRT) in the management of RPS remains controversial. No RCT and very few prospective trials of any type have been completed. We investigated the effects of preop XRT plus dose escalation with early postop brachytherapy (BT) on long term survival and recurrence in RPS. Methods: From 06/96 to 10/00, 40 patients (25 female) with resectable RPS were entered onto a phase I/II trial of preop XRT (50 Gy) plus postop BT (20-25 Gy). As previously reported, BT to the upper abdomen was associated with significant grade III-V postop toxicity, and from 12/98 on, BT was applied only to cases where the “field at risk” excluded the upper abdomen. Kaplan Meier survival curves were constructed; OS and recurrence free survival (RFS) were compared by log rank (SPSS 19.0). Results: Median age at study entry was 58 (38-70) yrs. Twenty nine patients presented to our center with primary disease (73%), and 22 (55%) had high grade tumors. All patients had preop XRT and total gross resection, while half (n=19) received BT. As of 12/2011, median follow-up time is 108 mos. For the entire study cohort, OS at 5 and 10 yrs were 70% and 65%, respectively; RFS at 5 and 10 yrs were 65% and 58%, respectively. RFS at 5 yrs was reduced in high vs. low grade RPS (50% vs. 83%, p=0.028), but by 10 yrs. was similar in high and low grade tumors (50% vs. 67%, p=ns). RFS was reduced in patients who presented with recurrent vs. primary disease (27% vs. 69% at 10 yrs., p=0.018), as was OS (36% vs. 76% at 10 yrs., p=0.034). Neither OS nor RFS was improved in the cohort of patients who received BT compared to the cohort who did not: at 10 yrs. RFS was 53% +BT and 62% -BT, while OS was 53% and 76%, respectively, p=ns. Conclusions: In this prospective study with mature follow-up, long term OS and RFS in patients who underwent combined preop XRT plus resection of RPS compare favorably with those reported in retrospective institutional and population-based series. Postoperative BT did not contribute to disease control.
Electronic Rapid Fitness Assessment: A Novel Tool for Preoperative Evaluation of the Geriatric Oncology Patient
Authors: Armin Shahrokni, Amy Tin, Robert J. Downey, Vivian Strong, Sanam Mahmoudzadeh, Manpreet K. Boparai, Sincere McMillan, Andrew Vickers, Beatriz Korc-Grodzicki
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: The American College of Surgeons and American Geriatrics Society recommend performing a geriatric assessment (GA) in the preoperative evaluation of older patients. To address this, we developed an electronic GA, the Electronic Rapid Fitness Assessment (eRFA). We reviewed the feasibility and clinical utility of the eRFA in the preoperative evaluation of geriatric patients. Methods: We performed a retrospective review of our experience using the eRFA in the preoperative assessment of geriatric patients. The rate and time to completion of the eRFA were recorded. The first 50 patients who completed the assessment were asked additional questions to assess their satisfaction. Descriptive statistics of patient-reported geriatric-related data were used for analysis. Results: In 2015, 636 older patients with cancer (median age, 80 years) completed the eRFA during preoperative evaluation. The median time to completion was 11 minutes (95% CI, 11–12 minutes). Only 13% of patients needed someone else to complete the assessment for them. Of the first 50 patients, 88% (95% CI, 75%–95%) responded that answering questions using the eRFA was easy. Geriatric syndromes were commonly identified through the performance of the GA: 16% of patients had a positive screening for cognitive impairment, 22% (95% CI, 19%–26%) needed a cane to ambulate, and 26% (95% CI, 23%–30%) had fallen at least once during the previous year. Conclusions: Implementation of the eRFA was feasible. The eRFA identified relevant geriatric syndromes in the preoperative setting that, if addressed, could lead to improved outcomes.
A survivorship program to improve quality of life of Hispanic/Latino breast cancer (BC) survivors.
Authors: Zeina A. Nahleh, Rosalinda Heydarian, Alok Dwivedi, Rebecca Pasillas, Luis Sanchez, Danielle Liss
Journal: Journal of Clinical Oncology (2017)

183 Background: We sought to determine whether Hispanic BC survivors in El Paso, TX would benefit from participating in a comprehensive multidisciplinary cancer survivorship program, by improvement of performance using the validated questionnaires: 1) Patient Health Questionnaire 9(PHQ9), 2) General Anxiety Disorder 7 (GAD 7), and SF36 Health related quality of life (HRQOL) questionnaires. Methods: After IRB approval, we recruited consecutive patients within the first 5 years post-diagnosis with Stages I-III BC and have completed active therapy. The program was staffed by an oncologist, a nurse practitioner, a nutritionist and a clinical psychologist. Survivors were seen every 3 months and questionnaires obtained. They were provided with a personalized treatment summary, dietary advices, in-depth one on one psychological assessment and interventions and an 8 week course based on Mindfulness Based Stress Reduction (MBSR). Results: 94 patients were recruited, 60 completed 12 months follow ups, and 33 completed 2 years follow ups. 91% were Hispanics. Mean age 55 years. 31% of participants were younger than 50 years. Stage 1 BC 38%, Stage 2 43% and stage 3 19%.75% received chemotherapy; and 74% received endocrine therapy. At baseline, PSC representing the mean for the SF-36 QOL Physical Health was 45.75, and the MSC for Mental Health was 43.7, both below the population norm (50.0). Mean scores for GAD7 was 7.3 and for PHQ9 7.62, both abnormal (&lt; 5). At 12 months PSC 46.02, MSC 46.1, GAD7 was 4.92; and PHQ9 was 5. At 24 months, PSC 45.65; MSC 47.02; GAD7 4.88; and PHQ9 4.52. Patients older than 50 years who attended the MBSR courses showed the most improvement in MSC and PHQ scores. Conclusions: BC survivors, predominantly Hispanics, benefited from participating in this program with improved mental SF36- HRQOL, a significant and long - lasting improvement in anxiety and depression at 12months and 24 months. Future efforts should focus on programs targeting younger cancer survivors who did not appear to derive a significant benefit overall. Also, additional efforts are needed to address physical -health related quality of life in cancer survivorship programs by introducing, as an example, exercise and pain control interventions.
Prevalence of high symptom burden and its impact on functioning and quality of life in patients with multiple myeloma 3-9 months following autologous transplant.
Authors: Qiuling Shi, Xin Shelley Wang, Nina Shah, Robert Z. Orlowski, Muzaffar H. Qazilbash, Loretta A. Williams, Tito R. Mendoza, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2014)

e19580 Background: Although multiple myeloma (MM) patients are expected to have lower disease burden post autologous hematopoietic stem cell transplantation (AuSCT), symptom burden and its impact on patient’s quality of life (QoL) have not been prospectively studied in this time period, when maintenance therapy may be implemented. Methods: 51 patients with MM were enrolled at 3 months post AuSCT. Patients rated symptom severity and interference weekly on the M. D. Anderson Symptom Inventory (MDASI-MM) for 6 months. Trajectory modeling identified a subgroup of patients who constantly reported higher symptom burden. Linear mixed-effect models and regression models were used to examine symptom impact on total symptom interference, and on QoL (EORTC-QLQ30 at 9 month). The effects of lenalidomide maintenance therapy on symptoms was examined. Results: Of 51 patients, 22 (43%) received lenalidomide maintenance therapy, 29 (57%) were in observation. Over time, the most severe symptoms were pain, fatigue, numbness, muscle weakness, and bone aches for all patients. Thirty-five percent of patients formed a high symptom burden cohort, which consistently reported moderate to severe symptoms (4.65 ±1.41 at baseline and 4.78 ±1.62 at month 6 for a composite score of these symptoms). Maintenance therapy with lenalidomide or other patient factors (age, sex, staging, BMI, race) were not predictive of high symptom burden. High symptom burden was predicted by higher post-AuSCT fatigue (est=0.58, P=0.002). Greater impairment of daily walking, work, and general activity was longitudinally related to higher levels of muscle weakness (est=2.43, P<.0001), fatigue (est=1.50, P=0.007), or pain (est=1.31, P=0.025). By end of study, patients with high symptom burden reported poorer QoL (61.1±26.5 vs. 82.1±16.9, P=0.003). A reduced physical functioning subscale score was related to higher levels of fatigue (P=.012) and bone aches (P=.005). Conclusions: Our study observed that 35% of MM patient consistently reported high symptom burden that was not related to use of maintenance therapy or other clinical variables, but significantly impacted on QoL and daily functioning.
Cancer vaccination trial with novel multiple peptides in previously treated advanced non-small cell lung cancer.
Authors: Takashi Hirose, Hidehiro Noda, Kentaro Okuda, Seiji Abe, Yuji Oto, Sojiro Kusumoto, Tomohide Sugiyama, Hiroo Ishida, Takao Shirai, Masanao Nakashima, Toshimitsu Yamaoka, Tohru Ohmori, Koji Yoshida, Yusuke Nakamura, Mitsuru Adachi
Journal: Journal of Clinical Oncology (2012)

e13029 Background: Cell division cycle associated gene 1 (CDCA1) and insulin-like growth factor-II mRNA binding protein 3 (IMP-3) are novel cancer-testis antigen overexpressed in non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the safety, efficacy, and immunological response of a novel peptide vaccination therapy, CDCA1 and IMP-3, in patients with previously treated advanced NSCLC. Methods: Human histocompatibility leukocyte (HLA)-A2402 positive advanced NSCLC patients who failed to standard therapy were enrolled if they had a performance status of 3 or less, were 80 years or younger, and had adequate organ function. The cocktail of 2 peptides was subcutaneously injected with 1 mL of incomplete Freund’s adjuvant to axillary or inguinal regions weekly. Immunological response was evaluated with enzyme-linked immunospot assay before and after vaccinations every 4 weeks. Results: From November 2009 through December 2011, 20 patients (13 men and 7 women; median age, 65 years; range, 36 to 78 years) were enrolled. CDCA1 and IMP-3 specific cytotoxic T lymphocyte responses were observed after vaccinations in 60% and 73% of patients, respectively. The overall response rate was 5% (95% CI, 0.1% to 24.9%) and stable disease rate was 55% (95% CI, 31.5% to 76.9%). The median survival time from the start of vaccination therapy was 7 months (range 1 to 26 months). The median progression free survival time was 3 months (range 1 to 15 months). One patient with interstitial lung disease (ILD) had acute exacerbation of ILD during vaccination therapy. The other 19 patients did not have any grade 3 or 4 adverse events. Conclusions: This vaccination therapy was effective and well tolerated in patients with NSCLC who failed to standard therapy, and therefore warrants further clinical studies.
Total neoadjuvant therapy for locally advanced rectal cancer.
Authors: Andrea Cercek, Campbell SD Roxburgh, Paul Strombom, Jesse Joshua Smith, Larissa K. F. Temple, Garrett Michael Nash, Jose G. Guillem, Philip Paty, Julio Garcia-Aguilar, Rona D. Yaeger, Zsofia Kinga Stadler, Neil Howard Segal, Diane Lauren Reidy, Jinru Shia, Efsevia Vakiani, Abraham Jing-Ching Wu, Christopher H Crane, Marc Jeffrey Gollub, Leonard Saltz, Martin R. Weiser
Journal: Journal of Clinical Oncology (2017)

662 Background: Current therapy for locally advanced rectal cancer (LARC) consists of 6 months of perioperative therapy, either with pre-operative chemo-radiotherapy (CRT) and post operative adjuvant chemotherapy (PAC) or total neoadjuvant therapy (TNT) with induction chemotherapy (ICT) followed by CRT then surgery. The aim of our study was to report on the safety, efficacy and complete response rates comparing TNT to PAC in a larger series of LARC patients (pts) at Memorial Sloan Kettering Cancer Center (MSKCC). Methods: Pts treated at MSKCC (2009-15) were analyzed based on the intended treatment schedule (TNT or PAC). 730 LARC pts were treated with CRT, of these 320 received neoadjuvant CRT and 308 received TNT. Results: In the TNT group 205 pts (73%) underwent surgery within 26 weeks of completion of treatment, of which 38 (19%) had a pCR. Of the 78 pts who did not undergo surgery within 26 weeks, 68 (87%) had a complete clinical response (cCR). In the PAC group 293 pts (92%) underwent surgery within 26 weeks and 45 (15%) had a pCR. Of the 27 pts who did not undergo surgery within 26 weeks 22 (81%) had a cCR. The median follow up was 25 mo in the TNT group and 29 mo in the PAC group. There was no statistically significant difference in the distant metastasis free survival between the treatment regimens, despite a higher number of cT4 and cN + tumors in the TNT group. Fewer distant recurrences were seen in pts who had evidence of T downstaging (P &lt; 0.001), N downstaging (P &lt; 0.005), the presence of a cCR (P = 0.005) or a pCR (P &lt; 0.005). Of the pts who received all treatment at MSKCC, comparison of dose of 5-FU and oxaliplatin between the preoperative (N = 249) and postoperative regimens (N = 101) was notable for a higher average dose received of both 5FU and oxaliplatin (p &lt; 0.005 and p &lt; 0.001) in the ICT group. Conclusions: These data add weight to the evidence already included in the NCCN guidelines that pre-operative chemotherapy as part of TNT is a viable treatment strategy with superior compliance and delivery of systemic therapy. Given the high complete response rate, TNT may be used as part of an organ preservation treatment strategy.
Efficacy, safety, and cost-effectiveness (CE) analysis of pegfilgrastim (P) and lenograstim (L) in patients (pts) with nonmetastatic breast cancer (nmBC) receiving myelosuppressive chemotherapy (mCT).
Authors: Anselmo Papa, Luigi Rossi, Federica Tomao, Fabio Ricci, Erika Giordani, Gian Paolo Spinelli, Giuseppe Lo Russo, Enrico Basso, Monica Verrico, Eleonora Zaccarelli, Giulia Rinaldi, Valeria Stati, Giulia Pasciuti, Martina Strudel, Federica Zoratto, Silverio Tomao
Journal: Journal of Clinical Oncology (2012)

e19620 Background: Neutropenia (N) is common in pts who receive mCT. This retrospective study was conducted to determine efficacy, safety and cost of single injection of P (6 mg) compared with daily L (263 μg), in primary prophilaxis of N in pts affected by nmBC, who received mCT. Methods: 50 women (median age 54 years) underwent to median 6 (range 4–8) CT doses with antracyclines +/- taxanes. At every cycle, 28 pts received daily L (median 5 injections from day 5 to 9), while 22 pts received one dose of P on day 2. Absolute neutrophil count, incidence of G3/G4-N, bone pain (BP: Numerical Rate Scale &gt;7) and CE analysis were evaluated. Results: In overall population (OP) incidence of G3-N and G4-N was 25% and 68%, respectively in L vs 22.7% and 41%, respectively in P; two cases (7%) of febrile N (FN) occurred in pts treated with L and three cases (13.6%) of FN in P. In 19 pts treated with FEC100 (10 pts L vs 9 pts P) we observed 0% of G3-N and 30% of G4-N in L while 33% of G3-N and 44% of G4-N in P. 31 pts received TAC/AC+T (18 pts L vs 13 pts P) with G3-N and G4-N 38.8% and 66.6%, respectively in L vs 15.3% and 30.7%, respectively in P. 18.2% of pts, who received P, had BP vs 35.7% in L. Reduction of CT doses was observed in 35.7% in L vs 41% in P. In Italy the cost of 1 injection of P was about 1489,00 euro compared with about 655,00 euro for 5 injections of L. Conclusions: In our experience, 1 injection of P was more effective and expensive than 5 daily administration of L to control N in OP and in particular in TAC/AC+T, while in FEC100, L was satisfactory with good CE profile. No difference about incidence of NF. Safety of P and L were similar with a lower incidence of BP in P.
A phase 2 randomized, double-blind, placebo-controlled trial of endocrine therapy ± radium-223 dichloride (Ra-223) in HER2- hormone receptor+ breast cancer patients with bone metastases.
Authors: Robert E. Coleman, Rui Li, Amrita G. Sawhney, Oana Petrenciuc, Hope S. Rugo
Journal: Journal of Clinical Oncology (2016)

TPS622 Background: Bone-metastatic breast cancer (MBC) treatment (tx) is limited. In a phase 2a study of bone-dominant MBC patients (pts), Ra-223, a first-in-class α emitter with targeted cytotoxic effect on bone metastases (mets), reduced bone biomarker levels with favorable safety (Coleman et al. Breast Cancer Res Treat 2014). This study evaluates efficacy and safety of Ra-223 v placebo (pbo), each + endocrine treatment (ET) in pts with HER2- estrogen receptor (ER)+ bone-dominant MBC (NCT02258464). Methods: Eligible pts are pre- or postmenopausal with HER2- ER+ bone-dominant MBC with ≥ 2 bone mets, soft tissue mets, and 1-2 prior symptomatic skeletal events (SSEs) (external beam radiotherapy, pathologic bone fracture, spinal cord compression, orthopedic surgery) who have received ≥ 1 line ET for MBC and are considered appropriate for further ET. Eligible pts must have evaluable disease (RECIST 1.1), be taking bisphosphonates or denosumab for ≥ 1 mo before study tx, have an ECOG score 0-1, and have adequate heme, renal, and liver function. Pts must not have had visceral or brain mets or leptomeningeal disease, or need chemotherapy for MBC and must not be suitable for everolimus for MBC. Pts are not eligible if they have prior Ra-223 tx or untreated spinal cord compression. Pts receive (1:1) Ra-223 50 kBq/kg IV or pbo q 4 wk (6 cycles) + ET + denosumab or bisphosphonates + best supportive care. Stratification is by geographic region, number of prior ET lines (1 v ≥ 2) for MBC, and number of prior skeletal events (1 v 2). Pts are assessed for efficacy and safety, and followed to SSE, radiologic progression, death, or withdrawal. The primary end point is SSE-free survival. Secondary end points are radiologic progression-free survival; overall survival; times to opioid use, pain progression, and chemotherapy; pain improvement rate; and safety. Assuming 1-sided α 0.1, power 90%, ~ 119 SSEs are needed for analysis. Time-to-event analysis will use a log-rank test, accounting for stratification. Kaplan-Meier estimates and survival curves will be given for each tx group. Safety analyses will be descriptive. Currently, 25 pts are randomized. Clinical trial information: NCT02258464.
Chemoembolization with super absorbent polymer microspheres (SAP-MS) loaded with doxorubicin (D) using escalating doses and adverse events (AE) in resectable hepatocellular carcinoma.
Authors: Renata D'Alpino Peixoto, Howard John Lim, Fady Ibrahim, Ellen Wasan, Jo-Ann Ford, David M. Liu
Journal: Journal of Clinical Oncology (2013)

e15084 Background: SAP-MS have demonstrated utility in the treatment of hepatocellular carcinoma (HCC) as a bland embolic and have demonstrated the ability to load and release D in vivo. Little is known about its toxicity profile. We aimed to determine if the dose and maximum plasma concentration (C max ) of D were correlated with occurrence of AE. Methods: A phase II dose-escalation study was performed to systematically evaluate AEs relating to outpatient-based D/ SAP-MS embolization in HCC using a D dose of 0-75 mg. D plasma levels were assessed at multiple time points (0.5, 2, 24 and 675h), in addition to standard analyses of liver and hematologic function. All AEs were reported following the Common Toxicity Criteria Version 3.0. A Pearson product-moment correlation was run to determine the relationship between C max and AE. Results: Of 25 patients enrolled, 24 were evaluable (6 = 0mg, 6 = 25mg, 6 = 50mg, 6 = 75mg). The side-effect profile was similar to other abdominal embolization procedures, with abdominal pain (62.5%), fatigue-like symptoms (41.7%), and nausea (41.7%) being the most common AE. There were no correlation between the administered doses of D and all grade AE (r = .209, p .328) or between C max 's of D and all grade AE (r = .321, p .127). All patients were discharged on the same day. There were no grade 4 or 5 AE and no hepatic decompensation. One patient required hospitalization 7 days post-procedure for groin puncture related complication. Conclusions: In our phase II dose-escalation study, patients experienced minimal post-embolization syndrome, which was not correlated with the amount of doxorubicin administered. The toxicities relating to SAP-MS delivery likely result from the embolic effect as opposed to dose response relating to the use of doxorubicin and can be managed on an outpatient basis. Clinical trial information: NCT01116635.
A Comparison of Fractionated Myeloablative Total Body Irradiation Schedules Combined with Chemotherapy As Conditioning for Allograft Bone Marrow Transplantation in Patients with Acute Leukemia: The Sarasin Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Yazid Belkacemi, Myriam Labopin, Sebastian Giebel, Gokoulakrichenane Loganadane, Leszek Miszyk, Eric Beohou, Mauricette Michallet, Gerard Socie, Nicolaas PM Schaap, Jan J. Cornelissen, Ibrahim Yakoub-Agha, Mohamad Mohty, Arnon Nagler
Journal: Blood (2016)
Renaissance of contact radiotherapy with RT 50 Papillon machine: A revival of new treatment option for early low rectal cancer?
Authors: Arthur Sun Myint
Journal: Journal of Clinical Oncology (2012)

e14149 Background: Local contact radiotherapy for early rectal cancer is an accepted treatment in most centers but still controversial in some centres. However, the old Philips machine is obsolete and many centers are unable to continue treating patients using this technique. A new RT 50 Papillon machine is now commercially available and there is a new hope for elderly patients and others who whish to avoid major surgery or permanent stoma. Methods: Although contact radiotherapy has been in clinical use for the past 80 years it is still not regarded as standard treatment in many centers around the world. This is due to the fact that there were no large randomized trials to prove its efficacy against standard surgical treatment. ICONE group has launched CONTEM trials, which are observational trials that combine Contact RT with TEMS for various stages of malignant rectal polyps. Results: ICONE group meets annually and organized courses for contact radiotherapy. So far, 10 centers in Europe have now been trained. We hope to start the CONTEM trials later this year. The data from these trials will be collected centrally in Nice and updated annually. The results will be published later. Conclusions: At present approximately 30-50% of patients with early (T1N0) low rectal cancer (&lt;6cm) are being over treated with APR. Revival of contact radiotherapy allows multimodality treatment for selected patients to avoid major surgery and permanent stoma. We hope the CONTEM trials will provide some evidence in this approach for suitable patients with early rectal cancer. [Table: see text]
Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study
Authors: Camelia Savulescu, Pavla Krizova, Agnes Lepoutre, Jolita Mereckiene, Didrik F Vestrheim, Pilar Ciruela, Maria Ordobas, Marcela Guevara, Eisin McDonald, Eva Morfeldt, Jana Kozakova, Emmanuelle Varon, Suzanne Cotter, Brita A Winje, Carmen Munoz-Almagro, Luis Garcia, Jesus Castilla, Andrew Smith, Birgitta Henriques-Normark, Lucia Pastore Celentano, Germaine Hanquet
Journal: The Lancet Respiratory Medicine (2017)