tbuckley/cabot-search huggingface dataset:
A Genome-Wide Analysis to Identify Novel Susceptibility Loci for Therapy-Related Acute Myeloid Leukemia
Authors: Kenan Onel, Jeffrey A Knight, Andrew D Skol, Thelma R Tennant, Mekhala Banerjee, Richard Walgren, Jin Shao, James M Allan, Michelle M Le Beau, Richard A Larson, Timothy Graubert, Nancy J Cox
Journal: Blood (2008)
Anemia management with epoetin beta in anemic patients with cancer receiving chemotherapy: Pananemia observational study on clinical practice.
Authors: S. Del Prete, F. Piantedosi, D. Rocco, F. Riccardi, B. Vincenzi, M. Bianco, C. Savastano, V. Montesarchio, M. Matarese, A. Sabia, A. Illiano, A. Pisano, M. Biglietto, G. Pistolese, L. Leo, L. Maiorino, A. Febbraro, R. Addeo
Journal: Journal of Clinical Oncology (2011)

e19630 Background: Chemotherapy-induced anemia has debilitating effects on patients with cancer. Treating anemia associated with chemotherapy and many cancers is often necessary. Epoetin therapy is associated with a slightly frequency of thromboembolic event (TEE). We investigated the safety profile of this treatment in clinical practice, the patient compliance, and the possible correlation between anemia and psychological distress frequently present in these patients. Methods: Overall, 1552 cancer patients in treatment with erythropoietin beta for anemia were enrolled in the observational study. The level of acceptance was evaluated using a self-administered Patient Satisfaction Questionnaire (PSQ) with ten items. Safety was assessed through recording of adverse events, laboratory parameters, and vital signs. The measurement of psychological distress was achieved using the Psychological Distress Inventory (PDI), a 13-item self-administered questionnaire, and the NCCN distress Thermometer administered at baseline and after 5 and 9 weeks. Patients were required to receive at least four weekly injections of Epo, expecting to receive ≥ 8 additional weeks of chemotherapy, and able to complete questionnaires. Results: Epoetin beta treatment was started on average at an Hb level of 9.46 g/dl, and it increased of 0,78 g/dl after 4 weeks of treatment. Only 2% of patients experienced a TEE. For psychological distress analysis, the overall response rate was 93 % at baseline, 90 % at week 5, and 86% at week 9. The increase of HB levels determined a reduction of percentage of patients with psychological difficulties. These data were confirmed by NCCN distress Thermometer that suggested an influence of anemic condition on psychological disorders. The PSQ questionnaires showed that a conspicuous group of patients (18%) marked troubles to accept the treatment. Conclusions: Our data confirm that when administered in accordance of Italian Health Agency and international guidelines, epoetin beta is effective and safety. The therapy is overall well accepted from the patients and determines also an amelioration of psychological distress.
Detection of new or additional significant breast disease by MRI compared to standard imaging in “high-risk” and “non-high–risk” patients.
Authors: Amy Lynn Banks, Rachel Titus, Marianne Melnik
Journal: Journal of Clinical Oncology (2013)

22 Background: Mammography is the standard of care for the early detection of breast cancer. Recently, studies have shown that Magnetic Resonance Imaging (MRI) has greater sensitivity in cancer detection. However, there have been reports identifying a high false positive rate. The aim of our study was to determine if breast MRI aids in the detection of new clinically significant disease, even in “low risk” patients, when compared to ultrasound (US) or mammography alone. Methods: A review of all patients who underwent breast MRI under the care of a single surgeon between 1/1/07 through 6/1/11 was conducted. Patients were categorized as high or non-high risk based on a history of breast cancer, genetic mutation, significant family history or &gt;20% lifetime Gail model risk. For this study a clinically significant disease is defined as a new cancer or high-risk lesion that requires close follow-up and monitoring. Results: A total of 163 patients had a breast MRI and all had concerning findings. Compared to US or mammogram, MRI identified new or additional disease that changed plans in 150/159 (94.3%) patients. Of these, MRI added clinically relevant findings in 85 patients (56.7%, p&lt;0.001). In those considered “high risk” MRI detected clinically significant disease in 37/76 (48.7%) and in 46/76 (60.5%) of the non-high risk group. 16 patients were &lt;40 and MRI found new disease in 2/7 (28.6%) high risk patients compared to 3/9 (33.3%) non-high risk patients. 48 patients were 41-50 years old and MRI detected new disease in 12/24 (50%) high risk patients compared to 13/24 (54.2%) non-high risk. Of the 37 patients aged 51-60, MRI found new disease in 11/19 high risk patients (57.9%) compared to 14/18 (77.8%) non-high risk. 50 patients &gt;60 years of age, MRI found new disease in 12/25 (48%) high risk patients compared to 16/25 (64%) who were non-high risk. Conclusions: We confirm that MRI provides extremely relevant data in identifying new or additional disease when compared to US or mammogram. MRI not only aided in finding additional disease in patients that were high risk but more importantly, MRI found pathology-proven new disease in non-high risk patients across all age groups. These results hold a substantial clinical implication in the ability to find new cancers or high-risk lesions early on, especially in non-high risk patients.
A phase II study of weekly nab-paclitaxel in combination with cisplatin as neoadjuvant chemotherapy in patients (pts) with locally advanced esophageal squamous cell carcinoma (SCC).
Authors: Fan Yun, Xinming Zhou, Youhua Jiang, Qixun Chen, Zhiyu Huang, Lei Gong, Haifeng Yu, Haiyan Yang, Jinshi Liu, Weimin Mao
Journal: Journal of Clinical Oncology (2014)

122 Background: This phase II study was aimed to define the pathological response rate and safety of combining weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy in pts with locally advanced esophageal SCC. Methods: Pts with resectable locally advanced thoracic esophageal SCC staged by EUS, CT and/or PET-CTscan. All pts received nab-paclitaxel (100 mg/m 2 , d1, d8, d22 and d29) and cisplatin (75 mg/m 2 , d1 and d22) as neoadjuvant chemotherapy, followed by esophagectomy.Postoperation: 2 cycles of adjuvant chemotherapy with same regimen was given in 4-6 weeks after the resection.The primary endpoint was pathological response rate. The second endpoints included R0 resection rate,down-staging rate, 3 years overall survival (OS) and disease-free survival (DFS). Results: From 01/2011 to 10/2012, 35 pts were enrolled. 31 male:4 females; IIA/IIB/IIIA/IIIB/IIIC in 3 (8.6%), 5 (14.3%),10 (28.6%), 8 (22.9%) and 9 (25.7%) pts. 30/35 pts went to surgery (85.7%). 30 had R0 resection (100%). Pathological complete response (pCR) was achieved in 4 pts (13.3%). Near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) in 2 pt (6.7%). Down-staging was observed in 19 of 30 patiens (63.3%). 5 pts did not going to surgery: 2 for progressive disease, 3 for refused. 24/30 pts (80.0%) received adjuvant chemotherapy, 7 pts (23.3%) received adjuvant chemoradiotherapy. Grade 3/4 toxicities in 35 evaluable pts during chemotherapy were as follow: neutropenia (11.4%), anemia (8.6%), thrombocytopenia (5.7%), nausea/vomiting (14.3%), neutropenia fever (8.6%), asthenia (20.0%). Surgical complications: 1 anastomotic leaks (3.3%). No treatment-related death. At a median follow up of 12 months (8~20mos), 29 pts were all disease-free survival. Conclusions: In pts with locally advanced esophageal SCC, weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy achieved a high pathological response rate and R0 resection rate. The toxicity was well tolerated. Evaluation of nab-paclitaxel and cisplatin in randomized trials was warranted. Clinical trial information: NCT01258192.
Primary pancreatic lymphoma: A population-based analysis using the Surveillance, Epidemiology and End Results database.
Authors: M. V. Mishra, S. W. Keith, X. Shen, T. Biswas
Journal: Journal of Clinical Oncology (2011)

303 Background: Primary pancreatic lymphoma (PPL) is a rare disease, accounting for only 0.5% of all pancreatic masses. The clinical presentation of PPL is similar to that of pancreatic adenocarcinoma and the two are difficult to distinguish radiographically. A paucity of literature exists on the epidemiology and outcomes of PPL. Given the limited case reports published on PPL, a comparison of the different treatment modalities has previously not been possible. Here, we present a series of 523 cases of PPL obtained from the Surveillance, Epidemiology, and End Results (SEER) database to investigate the tumor characteristics and compare the different treatment modalities. Methods: Patients diagnosed with a primary pancreatic lymphoma from 1973-2007 were identified. Data on patient and tumor characteristics as well as initial treatment with surgery or radiation was extracted. Chemotherapy information is not available through SEER. Overall survival was calculated using the Kaplan-Meier method. A multivariate analysis was performed to determine independent prognostic factors predicting for survival using a Cox proportional hazards model. Results: Fifty-eight percent of patients identified were male. The median age range at diagnosis was 65-69 years (range, 10-14 years – greater than 85 years). The most common histologic subtype in the present series was diffuse large B-cell lymphoma (DLBCL), which accounted for 71% of all patients. The 5-year overall survival for the group was 47%. Multivariate analysis indicates that age &gt;60 and a marital status of single were predictive of a decreased cause-specific and overall-survival specific survival (p&lt;0.05). Radiation therapy, but not surgery, was predictive of an improved overall survival (p&lt;0.05). Conclusions: PPL is a rare form of extra-nodal NHLs of the GI tract. Adjuvant radiation therapy for patients with a PPL should be strongly considered and a surgical treatment should be avoided if an early diagnosis is established. A prospective study evaluating this patient population will be difficult given the rarity PPL. We hope that this case series will provide a context in evaluating and treating patients with PPL. No significant financial relationships to disclose.
Functional subtyping with BluePrint 80-gene profile to identify distinct triple-positive subtypes with and without trastuzumab/chemosensitivity.
Authors: Pat W. Whitworth, Peter D. Beitsch, Michael C. Rotkis, James V. Pellicane, Mary Murray, Paul Baron, Carrie L. Dul, Angela Marie Mislowsky, Charles H. Nash, Paul D. Richards, Laura A. Lee, Lisette Stork, Femke De Snoo, Sarah Untch, Mark Gittleman, Stephanie Akbari, Jennifer Beatty
Journal: Journal of Clinical Oncology (2015)

114 Background: Classification by molecular subtype can aid in the selection of therapy for patients with breast cancer. However at present, the methodology for molecular subtyping is not standardized. The aim of the prospective NBRST study is to compare chemosensitivity as defined by pathological Complete Response (pCR) using the 80-gene BluePrint (BP) functional subtype profile vs. conventional IHC/FISH subtyping. Methods: The study includes women aged 18–90 with histologically proven breast cancer, written informed consent, no excision biopsy or axillary dissection, and no prior therapy for breast cancer. Neo-adjuvant Chemotherapy (NCT) was at the discretion of the physician adhering to NCCN approved or other peer-reviewed regimens. BP in combination with MammaPrint classifies patients into 4 molecular subgroups: Luminal A, Luminal B, HER2 and Basal. Results: 721 patients had definitive surgery. 58/335 (17%) IHC/FISH HR+/HER2- patients were re-classified by BP as Basal (57) or HER2 (1). 92/222 (41%) IHC/FISH HER2+ patients were re-classified as BP Luminal (67) or BP Basal (25). 7/164 (4%) IHC/FISH triple negative (TN) patients were re-classified as BP Luminal (5) or BP HER2 (2). NCT pCR rates were 3% in Luminal A and 9% in Luminal B patients versus 10% pCR in IHC/FISH luminal patients. The NCT pCR rate was 54% in BP HER2 patients. This is significantly superior (p = 0.02) to the pCR rate in IHC/FISH HER2+ patients (40%). BP Basal and IHC/FISH TN had a pCR rate of 35%. Functional BP subtyping divided the 137 IHC/FISH triple positive patients into two major subgroups: BP Luminal (n = 66, pCR = 11%) and BP HER2 (n = 60, pCR = 45%).11 patients were re-classified as BP Basal with pCR = 45%. Conclusions: Molecular subtyping using BP leads to a reclassification of 23% of tumors. The re-classification is most prominent in classically assessed triple positive patients where 48% of patients are re-assigned to the less responsive BP Luminal-type group vs. 44% of patients assigned to the responsive BP HER2-type group. These findings confirm the more accurate identification of molecular subgroups for treatment decision by BluePrint functional subtype classifier. Clinical trial information: NCT01479101.
Characteristics and treatment effect of senior patients with metastatic colorectal cancer (mCRC): A retrospective analysis.
Authors: J. Boudreault, F. Aubin, J. M. Ayoub, M. Sylvestre, C. S. Richard, M. A. Tehfe
Journal: Journal of Clinical Oncology (2011)

600 Background: Colorectal cancer affects many elderly patients as approximately 50% of cases are diagnosed in patients older than 70 years of age. We retrospectively studied characteristics, presentation, treatment and clinical course of our senior patients with (mCRC). Methods: Medical records of all patients ≥70 years with mCRC treated in our institution from 2006-2009 were reviewed. A multivariate Cox's proportional hazards model was applied to estimate the effect of chemotherapy (CT) on survival, while adjusting for other factors measured at time of diagnosis (age, sex, comorbidity, and number of metastases). Results: Ninety-four patients (48 men and 46 women) ≥70 year-old with mCRC were identified. Abdominal pain, fever, lower GI bleed and anemia were the most common presenting symptoms. Fifty-seven patients didn't receive CT mainly because of patient/family refusal, alteration of general status and presence of comorbidity. CT (N=37) was associated with an improved median survival (13.5 months) compared to non-treated group (2 months), with hazard ratio (0.20; 95% CI, 0.09 to 0.43; p&lt;0.00001). In the multivariate analysis, age (70-74 vs 75-79 vs ≥80 years), sex, comorbidity (0 vs 1 vs 2 vs ≥3), and number of metastatic sites (1 vs ≥2) were not independently associated with survival. ECOG-PS was not mentioned in the medical record of most patients. Sixty- three percent of the 70-74 year-old patients, 34% of the 75-79 year-old group, and only 23% of the ≥80 year-old patients received CT. Treatment benefit was seen with either 5-FU monotherapy (HR: 0.30; 95% CI, 0.12 to 0.77), Irinotecan-based (HR: 0.24; 95% CI, 0.07 to 0.74), or Oxaliplatin-based CT (HR; 0.07; 95% CI, 0.01 to 0.30). None of the patients had geriatric assessment prior to treatment. Conclusions: Most elderly patients with mCRC do not receive CT, yet treatment was associated with a clear survival benefit. The presence of multiple comorbidities did not affect treatment benefit. Although performance status could not be ascertained in this retrospective study, it likely influenced survival and the decision to treat with CT or not. Oncogeriatric assessment may be useful in better selecting elderly patients for systemic treatment. No significant financial relationships to disclose.
Margaret McCartney: We can save billions without cutting care
Authors: Margaret McCartney
Journal: BMJ (2017)

The Public Accounts Committee is doing what it does well: counting the pounds and asking where the pennies are. Its reports are worth reading, as examples of cross party truth seeking.

But what of its most recent report, NHS Treatment for Overseas Patients ?1 This concluded that the NHS and Department of Health must do “more to promote public confidence that the money due to the NHS is being recovered, and that the system is fair to taxpayers and to patients who are entitled to free care.”1 The committee says that a target of £500m is to be recouped in 2017-18.

Right on cue, Jeremy Hunt has announced a crackdown. From 1 April hospitals in England will have a legal duty to charge patients …
Patient experiences and preferences for survivorship care.
Authors: Kelly Westbrook Mitchell, Kevin Houck, Gretchen Genevieve Kimmick, Kathy J. Trotter, Jeffrey M. Peppercorn
Journal: Journal of Clinical Oncology (2013)

110 Background: The optimal method for delivery of care to over 2 million breast cancer survivors in the U.S. remains unclear, with multiple models currently in practice. This study involved a patient-centered investigation of experiences and preferences for breast cancer survivorship care. Methods: We conducted a single-institution, cross-sectional, self-administered survey of needs, experiences, and interests following initial breast cancer care at an academic multidisciplinary breast clinic. For 4 weeks, all patients presenting for routine oncology care were provided a survey at appointment check-in. Analysis is descriptive, with chi square testing used to evaluate demographic correlates of response. Results: 612 surveys were distributed, with a response rate of 66.8%. Median age of respondents was 56 (range 26-93); 71% were white, and 18% identified themselves as black. Over 55% had a college degree. Regarding ongoing care, 63% preferred to see a cancer specialist at least annually, and 30% wanted access to a cancer specialist as needed. Less than 15% preferred referral to a local practice, and less than 15% favored follow-up care from a specialized cancer survivorship clinic. Regarding visit content, over 90% felt assessment for disease recurrence was a priority on follow-up. A majority were interested in emotional and psychological support (52%). Nearly 40% of patients felt that assistance with non-cancer related health issues was very important in oncology clinic follow-up, but only 25% wanted a cancer specialist to provide general medical care. 42% reported receiving a summary of their cancer treatment. 37% reported receiving awritten plan or list of recommendations regarding care needed as a cancer survivor. White patients were less likely than non-white patients to receive a treatment summary (p &lt; 0.02) or a care plan (p&lt;0.005). Age and education were not correlated with receipt of these materials. Conclusions: Patients’ experiences and preferences regarding long-term management of breast cancer are varied. Many patients desire ongoing follow-up with their primary oncology team. Further evaluation of patients’ goals, needs, and an evidence-based approach to follow-up care is needed to guide optimal program design.
Arginine deiminase: A novel radiosensitizer in pancreatic cancer in vitro and in vivo.
Authors: Amit Deorukhkar, Nga Diep, Dev Chatterjee, Parmeswaran Diagaradjane, John S. Bomalaski, Sunil Krishnan
Journal: Journal of Clinical Oncology (2014)

221 Background: The benefits of chemoradiation therapy in patients with locally advanced pancreatic cancer (LAPC) are limited due to the inherent radioresistance of pancreatic cancer (PC) and high systemic toxicity of current radiosensitizers (e.g., gemcitabine). Hence, the search for newer radiosensitizers with unique anticancer properties continues. Single amino acid arginine starvation is a new promising therapeutic approach for solid tumors (e.g., PC), that are auxotrophic for non-essential amino acids. Arginine degrading enzyme, arginine deiminase (ADI), deprives cells of arginine and thereby exerts its anti-proliferative effects, especially in cancer cells deficient in enzyme argininosuccinate synthase (ASS1). Here we evaluate the effects of ADI-polyethylene glycol formulation (ADI-PEG20) as a radiosensitizer in PC. Methods: The toxicity of ADI-PEG20 in vitro was evaluated using XTT. Effect of ADI-PEG20 as radiosensitizer was determined by clonogenic cell survival. For in vivo, mice with PC tumor xenografts (Panc1), randomized into four groups, were treated with vehicle (PBS), ADI-PEG20 (5 IU/mouse; twice weekly), radiation (IR; 2 Gy × 5 times), and ADI-PEG20 with IR. Tumors were measured following treatment and the tumor re-growth delay time for each group was calculated. Immunohistochemical analysis of Ki-67 and VEGF was done on tumor tissues (paraffin sections) by routine immunofluorescence. Results: ADI-PEG20 selectively sensitized ASS1 deficient PC cells to IR at low, non-toxic concentrations (0.04 and 0.08 μg/mL for 72 h; DER at 10% SF for Panc1 was 1.39 and 1.52; for Miapaca-2, 1.09 and 1.25 respectively), but not ASS1 positive cells (L3.6pl). In vivo, ADI-PEG20 profoundly sensitized PC cells to IR. IR treatment alone delayed the tumor doubling time (7.6 ± 1.7 days compared to the non-treated controls); however, combining ADI-PEG20 with IR delayed the tumor growth by an additional 10 ± 1.3 days (p&lt;0.05). Immunohistochemical analysis of tumor tissues suggested that ADI-PEG20 with IR down-regulates the expression of Ki-67 and VEGF. Conclusions: ADI-PEG20 potently radiosensitizes PC cells in vitro and in vivo. The detailed molecular mechanism of this radiosensitization warrants further investigations.
Evaluation of bombesin receptor (BB2r) targeted radiotherapy, chemotherapy, and zoledronic acid in a preclinical model of prostate cancer.
Authors: S. Haddadin, T. L. Rold, T. J. Hoffman
Journal: Journal of Clinical Oncology (2011)

e15122 Background: The majority of patients who die of prostate cancer have metastatic castration-resistant disease (CRPC). Available therapies provide modest prolongation of survival measured in months. We have previously demonstrated that the use of BB2r targeted radiation therapy (TRT) using 177Lu-DOTA-8-AOC-BBN (7-14)NH2 in combination with chemotherapy suppressed tumor growth in SCID mice in both flank and intra-tibial models employing PC-3 cells; however, significant bone loss resulting in tibial fracture was a predominant deterrent to prolonged subject survival. Since zoledronic acid (ZA) is effective in treatment of diseases with pathologically increased osteoclast-mediated bone resorption, including metastatic bone disease, we postulated that by adding ZA, tibial fractures can be delayed resulting in improved outcomes. Methods: In a randomized study, SCID mice received intra-tibial inoculation of PC-3 cells on day (-7). Therapy (Table) was started on day(+1). Daily weight and body condition scores (BCS) and weekly radiographs were collected. Subjects were given two “21day” cycles. Subjects were removed upon reaching predetermined endpoint criteria including tibial fracture, BCS of ≤-2, significant weight loss. Results: At study termination(Day 86) 83% of the mice in Arm C(TRT+CT+ZA) and 80% of mice in Arm A(CT+ZA) had survived as compared to 29% of the mice in Arm B(CT+TRT). Health status of mice in Arm B consistently declined over the study duration, with subject removal beginning at Day 20resulting from stated endpoint criteria. Conclusions: ZA used in combination with BB2rTRT and chemotherapy is effective in prolonging short term survival in a preclinical model of CRPC. Further studies are required to ascertain if the addition of BB2r TRT to a ZA+chemotherapy regimen results in significantly improved outcomes. Therapy/day Mon Tue Wed Thu Fri Sat Sun Arm A (n=10) CT ZA CT CT CT ZA CT Rest Rest Arm B (n=7) CT CT CT TRT CT CT Rest Rest Arm C (n=6) CT ZA CT CT TRT CT ZA CT Rest Rest Control (n=2) A therapy cycle was given every 3 weeks; Chemotherapy (CT): docetaxel(ip) D1,8,15/capecitabine(po) D1-5,8-12;ZA:subcut 100mcg/kg D1,4,8,11,15,18; TRT(ip) D3,10,17.