tbuckley/cabot-search huggingface dataset:
Ten-year outcomes of accelerated partial breast irradiation compared with whole breast irradiation: A matched-pair analysis.
Authors: Jessica Wobb, Michelle Wallace, Chirag Shah, Hong Ye, Maha Saada Jawad, Kimberly Marvin, Inga S. Grills, Peter Y Chen
Journal: Journal of Clinical Oncology (2013)

55 Background: Breast conserving therapy (BCT) represents a standard of care in the management of early stage breast cancer; while adjuvant radiation therapy was traditionally delivered using whole breast irradiation (WBI), accelerated partial breast irradiation (APBI) offers an alternative to WBI that shortens the duration of treatment and may improve toxicity profiles and quality of life. The purpose of this analysis is to compare clinical outcomes of patients treated with WBI versus APBI. Methods: A total of 3,009 patients were treated with BCT at single institution between 1980 and 2012 with 2,528 patients receiving WBI and 481 patients receiving APBI (interstitial or balloon-based). A matched-pair analysis was performed with patients matched according to age (+/- 3 years), T stage (Tis vs T1 vs T2), and estrogen receptor (ER) status (+/-). All patients had a minimum of 12 months of follow up. A total of 247 matches were made with clinical outcomes compared using the Kaplan-Meier method. Results: Mean follow-up was 8.1 years for WBI vs. 7.8 years for APBI (p&lt;0.001), a difference of less than 4 months. There were no differences with respect to age (p=0.88), tumor stage (p=1.0), or ER status (p=1.0). Long-term cosmesis was good to excellent in 94% vs. 95% of patients (p=0.78). WBI patients demonstrated a trend for slightly larger tumors (13.0 vs. 11.4 mm, p=0.06). At 10 years, no difference in ipsilateral breast tumor recurrence (4% vs. 4%, p=0.11), regional recurrence (1% vs. 1%, p=0.20), distant metastases (3% vs. 6%, p=0.47), disease free survival (93% vs. 91%, p=0.10), or contralateral breast failure (9% v. 3%, p=0.06) was noted when comparing WBI and APBI. In addition, 10 year cause-specific survival (94% v. 93%, p=0.72) and overall survival (83% vs. 75%, p=0.34) were similar. Conclusions: At 10 years, no differences in locoregional recurrence, distant metastasis or survival were found between patients undergoing whole breast irradiation or accelerated partial breast irradiation using interstitial catheter or balloon-based brachytherapy. These data represent one of the only APBI series with prolonged follow-up and show similar outcomes in a matched group of patients undergoing WBI or APBI.
Post prostatectomy multimodality adjuvant therapy for patients at high risk for prostate cancer relapse
Authors: F. Jiang, H. Ruckle, D. Ornstein, T. Ahlering, F. Howard, M. Lilly
Journal: Journal of Clinical Oncology (2008)

16053 Background: Adjuvant systemic therapy improves survival for many loco-regional cancers, but few data describe adjuvant therapy of prostate cancer. We have conducted a pilot study of multimodality adjuvant therapy (MAT) following radical prostatectomy (RP) in subjects at high risk subjects for disease recurrence. Therapy was modeled after current adjuvant treatment of breast cancer, and included both adjuvant combination chemotherapy and prolonged androgen ablation. Methods: Subjects with high-risk CaP (predicted five year relapse risk >25% by 1999 Kattan post-op nomogram and/or persistent PSA after surgery) were offered MAT. Therapy included 6 cycles of combination chemotherapy Q 3wks (docetaxel [=doc] 70 mg/m2, estramustine 280 mg TID × 5 d, or doc 70 mg/m2, carboplatin AUC5), followed by 5 yr of androgen deprivation (leuprolide plus bicalutamide). Subjects with pT4 Dz or multiple positive margins were also offered adjuvant radiation therapy following chemotherapy. Results: Twenty-eight high-risk subjects received MAT. Rx started an average of 78 d after RP. Clinical parameters include: mean age 59.9 yr; Gleason 8–10 64%; pT3b/4 57.1%; N1 70.3%, positive margins 57.1%. Mean predicted relapse risk (Kattan) was 63.6% (2 yr) and 76.4% (5 yr). Ave. chemo cycles = 5.8. Twenty subjects received doc/estramustine, and eight received doc/carboplatin. 7/28 received XRT as part of therapy. Maximum followup is 76.6 mos, ave. followup is 31 mos from RP. There have been no biochemical (PSA) relapses and 26/28 (93%) remain free of disease progression. 2/28 (7%) subjects relapsed clinically, without an elevated PSA at relapse, and both died of cancer. Major chemo toxicities are Gr3–4 neutropenia (65%), edema (30%), DVT (25% with doc/estramustine). Conclusions: Adjuvant MAT is tolerated by high-risk subjects. Biochemical or clinical failures in subjects treated with MAT are uncommon within this followup period; however, disease relapse in these subjects is aggressive and fatal. Doc/estramustine has an excessive risk of DVT, even with prophylactic coumadin. Doc/carboplatin has little risk of DVT and is our current chemotherapy choice in the adjuvant setting. PSA may be inadequate as the sole method to monitor high risk subjects treated with these adjuvant therapies. No significant financial relationships to disclose.
Hepatic artery infusion for recurrent or chemotherapy-resistant hepatic malignancy.
Authors: H. J. Wanebo, S. R. Sanikommu, C. Taneja, G. Begossi, F. J. Cummings, J. Belliveau
Journal: Journal of Clinical Oncology (2011)

e14151 Background: Previously treated hepatic colorectal metastases (CRC) and advanced hepato cellular cancer (HCC) are tumor challenges frequently unresponsive to systemic chemo therapy (CT). We reviewed survival outcome in chemo-resistant/high-risk patients following hepatic artery infusion (HAI) in 21 CRC pts, 10 HCC pts, and 6 miscellaneous metastatic cancers. Methods: Patient groups: 21 CRC pts (16M, 5 F), mean age 63, 16 had metachronous (DFI-17 mos), and 5 synchronous CA; liver extent: 76% multiple (>5) mets or extensive bilateral, CEA (ng/m), >100, 8 pts > 50 (3 pts) < 5 (3 pts) and , NA – 7 pts. Previous CT: FU/LV (11pts), oxaliplatin (OX) or irinotecan (IR) (10 pts). Liver surgery: partial resection/RFA – 9 pts. HCC: (9 PTS), cholangio CA(1), M/F 5/5; av. age 63. Previous RX hepatic lobectomy 4 pts, RFA/TACE – 3 patients. Miscellaneous GP (therapy): Hepatic lobectomy + HAI were done in metastatic lung (1), Breast (1), advanced gall bladder cancer (GBCA; T 3-4; 2 pts); HAI alone was done in Br. CA (1) carcinoid (1) treatment protocols: CRC protocol: HAI-FUDR 12-15mg/kg/d, dexamethasone 2mg.kg/d, leukovorin 20mg/m2 /d (14 d) plus bolus infusion (d1), oxaliplatin (OX) 130mg/m2 (or cisplatin [CIS] 100mg/m2 d1); systemic RX: d20-30. OX I.V. 130mg/m2, capecitabine 750-1,000mg/m2/d x 10 days (also used in Miscel. Grp.) HCC Protocol: HAI-14 d as in CRC protocol. Bolus infusion d1-doxorubicin 75mg/m2 or OX or CIS as in CRC schema. Results: CRC: OS-CRC post start HAI = med/16mos., 2yr/5yr = 27%/6%. HCC OS = 9 mos. Median (3-12 mos in 9 evaluable pts.; 1 HCC pt, with recurrence 2 yr. post central hepatectomy was treated over 3.5 yrs. with HAI + RFA/TACE – (OS-67 mo).Miscellaneous group included lung (11 mos) Br CA (23, 9 mos) adv. carcinoid (3 mos), GBCA (2 pts > 60 mos), major complications; pump malfunction (4 pts), misperfusion (2) pts, infected pocket (2) pt, duodenal fistula (1) pt. Conclusions: Hepatic artery infusion alternating with systemic chemo therapy has apparent survival benefit in selected patients with persistent or progressive chemo resistant malignancy from metastatic CRC, HCC, or selected miscellaneous cancers (breast, lung, liver, gall bladder cancer) and warrants further study.
Impact of a gene expression-based tissue of origin test on diagnosis and recommendations for first-line chemotherapy.
Authors: M. Laouri, J. S. Nystrom, M. Halks-Miller, W. D. Henner
Journal: Journal of Clinical Oncology (2010)

10579 Background: The Pathwork Tissue of Origin Test for FFPE is a microarray-based gene expression test that aids in the diagnosis of poorly differentiated and metastatic tumors. An accurate diagnosis increases the likelihood that appropriate treatment can be administered. This study evaluates the impact of the Tissue of Origin Test results on the diagnosis of the primary site and the impact on recommended first-line chemotherapy based on the NCCN Guidelines. Methods: A consecutive series of 284 clinical samples with Tissue of Origin Test results were categorized according to the clinician's pretest diagnosis, using ICD-9 codes and the biopsy site. The test result was compared to the original submitted diagnosis to identify changes in diagnosis of primary site, and to the NCCN Guidelines to identify potential changes in recommended therapy. Results: 85% of study cases were metastatic malignancies. 64% had nonspecific diagnoses of primary site, and for the remaining 36%, the submitting clinician provided a leading diagnosis for primary site, most likely indicating an unresolved differential. The test predicted either a change from nonspecific to a specific site or a change from one primary site to another in 81% of cases. For 15% of cases, the Tissue of Origin Test confirmed the submitted diagnosis. Overall, based on test prediction and the NCCN guidelines, first-line chemotherapy treatment would change for 63% of the cases. Conclusions: The Tissue of Origin Test is an aid to diagnosis for cases in which the location, histology or IHC results make it difficult to reliably diagnose the primary site. For patients with unidentified primary sites, the Tissue of Origin Test results are likely to change recommended first-line chemotherapy for the majority of patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pathwork Diagnostics Pathwork Diagnostics Pathwork Diagnostics
Ewing’s sarcoma (EW): Long-term favourable outcome in children with combined modality therapy and conservative surgery
Authors: N. Delepine, F. Delepine, H. Cornille, S. Alkalaf, A. Tabbi, G. Delepine
Journal: Journal of Clinical Oncology (2005)

8561 Background: To assess the effect of surgery on local tumor control of EW in children, with localized disease. 25 years ago, many authors emphazized the crucial role of surgery in EW. Recently, others plae again for radiotherapy in local control. Methods: 21 patients (p.) <18 y received DD2 protocol already described:short induction -6weeks-, systematic surgery and six alternate drugs (cyclophosphamide,pirarubicine,ifosfamide,cisplatine,vincristine-actinomycine D). We calculated the cumulated incidence of disease recurrence, late complications, overall and event free survival. Results: Out of the 39 p. treated on first hand from Nov 1985 to Jan 2000, 21 were under 18 years at diagnosis, 13 girls, 8 boys. The median tumor volume was 284 cc. Locations were rib (4), femur (4), maxillar (1), radial (1), tibial (3), vertebral (1), sacral (1) iliac (5) fibula (1). All received CT, en-bloc surgery. Contaminated resection led to 45 grays irradiation: 2 sacral and 1 rib. In nov 04, 20/21 are EFS with a median FU of 153 months (range: 58 -227) 1 p. died (metastatic at 39 months). No local recurrence occured. Orthopedic results were excellent or good (18), fair (2), poor (1 amputated for infection of the prosthesis) following MSTclassification. 2 p. presented a colic adenocarcinoma, respectively 13 and 15 y following EW. They were 15 and 18 y old at diagnosis and had sacro-iliac locations irradiated post surgery. 8 were married, 3 had 6 normal children. 1 man was sterile (the same as colic cancer). All have a normal social life. Conclusions: This serie confirms the excellent outcome of children with EW (at the opposite of adults treated with the same scheme already published), the high value of early conservative carcinologic surgery, the high risk of secondary radio-induced maligancy. This study emphasis the importance of systematic surgery in EW. Long term follow-up is mandatory to detect late recurrences or secondary maligancies. No significant financial relationships to disclose.
Efficacy of platinum chemotherapy agents in the adjuvant setting for adenosquamous carcinoma of the pancreas.
Authors: Aaron Tyler Wild, Avani Satish Dholakia, Katherine Y. Fan, Rachit Kumar, Dan Laheru, Luis A. Diaz, Lei Zheng, Dung T. Le, Ana De Jesus-Acosta, Susannah G. Ellsworth, Amy Hacker-Prietz, K Ranh Voong, Matthew Weiss, Ralph H. Hruban, Phuoc T. Tran, John L. Cameron, Timothy M. Pawlik, Christopher Lee Wolfgang, Joseph M. Herman
Journal: Journal of Clinical Oncology (2013)

e15028 Background: Pancreatic adenosquamous carcinoma (PASC) is a rare morphological subtype of pancreatic adenocarcinoma. PASC accounts for only 1-4% of exocrine pancreatic cancers and carries a particularly poor prognosis. Due to the rarity of PASC, studies of therapies specifically targeting this histopathologic entity are exceedingly limited. Based on efficacy exhibited by platinum agents against squamous carcinoma of other body sites, addition of these agents to adjuvant regimens may benefit patients with PASC. This retrospective study was performed among the largest series of patients with PASC identified to date in order to determine whether addition of platinum agents improves survival. Methods: Records of all patients who underwent pancreatic resection at our institution from 1986-2012 were reviewed to identify those with PASC. Demographic, surgical, pathologic, adjuvant therapy, and survival data were collected. Patients were divided into non-platinum (NPG) and platinum (PG) groups based on whether or not they received a platinum agent as part of adjuvant therapy. Results: In total, 62 patients with PASC were identified among 5,627 cases (1.1%). Fourteen patients received a platinum agent in the adjuvant setting (PG), while 48 did not (NPG). These two groups were comparable in regard to median age (65 vs. 69 yrs, p=0.34), gender (36 vs. 46% female, p=0.50), performance status (78 vs. 79% ECOG 0, p=0.98), histologic grade (86 vs. 77% grade 3, p=0.49), positive resection margins (14 vs. 29%, p=0.26), lymph node involvement (71 vs. 79%, p=0.54), median tumor diameter (4.0 vs. 4.3 cm, p=0.64), and proportion receiving radiotherapy (57 vs. 42%, p=0.31). PG patients received a median of 5.5 cycles (IQR, 3.3-6.0) of platinum chemotherapy, with 10 patients (71%) receiving cisplatin-based regimens and 4 (29%) receiving oxaliplatin-based regimens. PG patients experienced significantly longer median survival (19.1 months, 95% CI 12.8-25.4) compared to NPG patients (9.8 months, 95% CI 7.3-12.4) (p=0.024). Conclusions: Addition of a platinum agent to adjuvant regimens for resected PASC may improve survival among these high risk patients, though collaborative prospective investigation is needed.
Identification of barriers to clinical trials: The impact of education level.
Authors: J. R. Eads, T. L. Albrecht, B. Egleston, J. S. Buzaglo, R. B. Cohen, L. Fleisher, T. Foster, M. Katz, T. Kinzy, S. Manne, D. M. Miller, S. M. Miller, S. Raivitch, N. Roach, A. Silver, N. J. Meropol
Journal: Journal of Clinical Oncology (2011)

6003 Background: Patient (pt) participation in clinical trials remains low. We previously described psychosocial and practical barriers to enrollment (J NCCN, 2007). During development of an intervention to improve pt preparation for consideration of clinical trials, we conducted a survey to identify pt characteristics associated with knowledge and attitudinal barriers (NIH R01 CA127655). Methods: Eligible pts were adults with a cancer diagnosis scheduled for their first medical oncologist visit. Informed consent was obtained to participate in a survey before the initial consultation. The survey included demographic information and an assessment of potential clinical trials barriers. Items included 19 correct-incorrect knowledge questions and 29 attitudinal barriers that were assessed on a 5-point Likert scale (1=strongly disagree, 5=strongly agree; 4-5 scored as “positive”). Cronbach’s alphas and factor analysis were used to develop four attitudinal barriers subscales: fears and emotions, knowledge and finances, logistics, and mistrust of the medical system. Multiple linear regression analysis examined the relationship of demographics with barriers. Results: 156 pts enrolled: 40% female, 23% African American (AA), 42% college educated, mean age 58.7 years. Non-AA pts answered more knowledge questions correctly (mean 11.5 vs. 9.1, p=0.002) as did college educated pts (mean 13 vs. 9.5, p<0.001). Race was not associated with attitudinal barriers in the multivariable analysis. College education was associated with fewer attitudinal barriers (fears and emotions, p=0.092; knowledge and finances, p=0.005; logistics, p<0.001; mistrust of the medical system, p=0.049). Females scored higher on the fears and emotions subscale (p=0.015). Most commonly cited attitudinal barriers were fear of side effects on a clinical trial (54% of pts), not knowing where to find a clinical trial (40%) and unwillingness to travel extra distance for a clinical trial (39%). Conclusions: Lower educational level and female gender, but not race, are independently associated with barriers to clinical trials, suggesting a tailored approach to addressing these barriers is warranted. Socioeconomic status rather than race should be a focus of these efforts.
Target-based therapeutic matching in early-phase clinical trials in patients with advanced colorectal cancer and <i>PIK3CA</i> mutations.
Authors: Filip Janku, Aung Naing, Gerald Steven Falchook, Apostolia Maria Tsimberidou, Vanda M. T. Stepanek, Siqing Fu, Sarina Anne Piha-Paul, Rajyalakshmi Luthra, David S. Hong, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2012)

459 Background: Therapeutic matching based on underlying molecular abnormalities showed promising results in patients with diverse advanced cancers in early phase clinical trials. PIK3CA mutations may predict response to therapies with PI3K/AKT/mTOR inhibitors. Methods: Tumors from patients with colorectal cancer referred to the Clinical Center for Targeted Therapy (Phase I Program) were analyzed for PIK3CA mutations. Patients with PIK3CA mutations were treated, whenever feasible, with agents targeting the PI3K/AKT/mTOR pathway. Results: Of 194 patients analyzed, 31 (16%) had PIK3CA mutations. Of 194 patients 175 (90%) were assessed for the presence of KRAS mutation. Patients with PIK3CA mutations had higher prevalence of simultaneous KRAS mutations than patients with wild-type (wt) PIK3CA (21/30, 70% vs. 63/145, 43%; p=0.009). Of the 31 patients with PIK3CA mutations, 17 (55%) were treated in clinical trials containing a PI3K/AKT/mTOR pathway inhibitor (median age, 57; median number of prior therapies, 4). Of these 17 patients, none achieved a partial or complete response (PR/CR) and only 1 (6%, 95% CI 0.01-0.27) patient had stable disease for more than 6 months (SD&gt;6), which was not significantly different from the SD&gt;6/PR/CR rate of 16% (11/67; 95% CI 0.09-0.27) in colorectal cancer patients without PIK3CA mutations treated on the same protocols targeting the PI3K/AKT/mTOR pathway (p=0.44). The median progression-free survival was only 1.9 months (95% CI 1.5-2.3). Conclusions: Heavily pretreated patients with PIK3CA-mutant advanced colorectal cancer do not seem to benefit from protocols incorporating PI3K/AKT/mTOR inhibitors. PIK3CA mutations are associated with simultaneous KRAS mutations, which might account for therapeutic resistance.
A new model of care: An advanced practice radiation therapy role.
Authors: Elizabeth Lockhart, Eric Gutierrez, Padraig Richard Warde, Kate Bak, Laura Zychla, Amanda Bolderston, Donna Lewis, Marcia Smoke, Julie Wenz, Lynne Nagata, Michelle Ang, Nicole Harnett
Journal: Journal of Clinical Oncology (2014)

131 Background: Due to the rising incidence of cancer, increasing complexity of cancer treatment and growing resource constraints, there is demand for innovative interprofessional models of care. Cancer Care Ontario (CCO), in collaboration with Ontario’s Ministry of Health and Long-Term Care, launched the Clinical Specialist Radiation Therapist (CSRT) project to investigate a new advanced practice (AP) radiation therapy (RT) role. Methods: A series of pilot phases commenced in 2004. A system wide implementation phase began in 2010. The overall goal of the project was to enable CSRTs to assume responsibility for certain key radiation medicine activities, optimize RT team functioning, and improve quality of care. This was to be achieved by applying advanced clinical, technical and professional RT competencies. A project team coordinated assessment of new position proposals, implementation activities, and data collection. Work towards formalizing the role is being conducted through partnerships with cancer centre administrations and the national professional association for RTs. Results: Currently there are 17 CSRTs in 6 of 14 Ontario cancer centres, practicing in palliative and disease-site specific positions. The provincial total will be 24 CSRTs in 10 centres by Fall 2014. Data show a major impact on patient throughput and wait times, with significant increased capacity in some clinics. CSRTs’ impact within their departments is being evaluated with regards to: 1) capacity building, 2) quality of care, and 3) knowledge translation (KT). In terms of role formalization, 6 positions are now considered permanent within their centres and the first iteration of a national certification process is anticipated for fall 2014. Conclusions: The CSRT project is aligned with CCO's priorities of improving Ontario’s cancer system performance by implementing innovative models of care and providing high quality care. This jurisdictional implementation project has demonstrated that an AP RT role can be successful in addressing system pressures and improving quality of care and innovation in Radiation Medicine. Further work is necessary to develop and formalize this AP role and leverage learnings for national implementation and future models of care work.