tbuckley/cabot-search huggingface dataset:
Retrospective analysis of invasive lobular carcinomas of the breast: Implications for diagnosis and treatment.
Authors: V. Velker, G. Poloquin, V. Poloquin, C. M. Hamm
Journal: Journal of Clinical Oncology (2010)

e11089 Background: Invasive lobular carcinoma (ILC) accounts for 10%-15% of all invasive breast carcinomas. When compared to invasive ductal carcinomas (IDC), it has increased multifocality, lower mammographic sensitivity, higher mastectomy rates, and metastases to unusual locations such as the GI tract and peritoneum. A less common subtype is the mixed presentation of invasive ductal and lobular carcinomas (IDLC), though the clinical significance of this distinction is not well understood. Investigating the differences between these subtypes may lead to improved treatments. Methods: A database of 1182 patients presenting between 2000-2005 at the Windsor Regional Cancer Centre yielded a consecutive series of 64 ILC (5.4%) and 63 IDLC (5.3%) patients. The charts were retrospectively reviewed analyzed for parameters including tumour pathology, use of diagnostic imaging, treatments received, prognostic factors and disease progression. Results: Compared to ILC, IDLC was significantly more likely to be grade 3 (p = 0.01), yet ILC was significantly more likely to present as stage IV disease than IDLC (p = 0.04). ILC was less likely than IDLC to be treated by lumpectomy only (p = 0.04), possibly secondary to the previous notions that lobular carcinomas had a higher likelihood of bilateral presentation than IDC. IDLC was similar to ILC in most other parameters, including equally high rates of bilaterality, multifocality and rates of contralateral prophylactic mastectomies. For ILC, most data agreed with findings of previous studies. There was no statistically significant differences in survival between IDC and IDLC. Mammography detected 91/122 (74%) cancerous breasts, in keeping with the previously reported sensitivity rates of mammographic screening for lobular carcinoma. Conclusions: IDLC and ILC do not have significantly different clinical presentations except that IDLC is more likely than ILC to be grade 3, but ILC more likely to be stage IV at presentation. This study confirms previous findings on ILC and IDLC, including difference in diagnosis and surgical management. No significant financial relationships to disclose.
Derivation and validation of a risk model for emergency department palliative care needs assessment using the Screen for Palliative and End-of-Life Care Needs in the Emergency Department (SPEED).
Authors: Danielle Moulia, Zachary O. Binney, Tammie E. Quest, Paul DeSandre, Sharon Vanairsdale, A. Cecile Janssens
Journal: Journal of Clinical Oncology (2014)

22 Background: A key setting for the provision of palliative care is the emergency department (ED) where important decisions regarding treatment and next site of care are determined; however identifying patients who would benefit from a palliative care consult is an ongoing challenge. The (SPEED) is a 5-question tool that assesses unmet palliative care needs. Methods: We performed a retrospective derivation and temporal validation of a risk model for a palliative care event (PCE) among cancer patients with an ED visit and subsequent hospital admission using data available upon arrival, including data from the SPEED tool. A PCE was defined as a palliative care consult, discharge to hospice, or in-hospital death. We developed a multivariate logistic regression model to predict PCEs. We assessed model performance using a receiver operating characteristic curve and visual inspection of quintile plots. Results: Eleven factors were identified as predictive of a PCE, including SPEED score, proxy SPEED informer, age, EMS arrival, emergent or immediate ED acuity, the number of ED visits within the last 90 days, metastatic cancer, cardiac arrhythmias, coagulopathy, depression and weight loss. In validation, the risk model had an area under the curve of 0.72 and calibration showed an underestimation of risk in the second and third quintiles. Conclusions: A risk model based on SPEED score has been successfully derived, but needs a larger dataset for proper validation. If the predictive ability of the model is confirmed, a risk model can efficiently identify cancer patients arriving to the ED who may benefit from early initiation of a palliative care consult.
A phase I study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer.
Authors: B. Halmos, J. A. Bokar, P. Fu, D. J. Adelstein, R. A. Juergens, M. B. Rodal, A. Dowlati
Journal: Journal of Clinical Oncology (2011)

e14644 Background: Metastatic gastroesophageal carcinoma is a devastating illness and there is a strong need for improved therapies incorporating novel targeted agents, such as anti-angiogenic agents into active chemotherapy programs. We set out to assess the safety and tolerability of the dual VEGFR/EGFR inhibitor, vandetanib (V) in combination with two active chemotherapeutic agents in this illness, oxaliplatin (O) and docetaxel (D). Methods: Phase I study (NCT00732745) with a standard 3+3 dose escalation design with the primary aim to determine the MTD of V added to OD chemotherapy in advanced GE cancer. GE cancer pts with either adeno or squamous cell histology were eligible with adequate organ function and ECOG PS of 0-1. Patients could not have received prior chemotherapy for advanced disease. Results: Initial treatment for the first cohort consisted of O at 100mg/m2 day 1, D at 35 mg/m2 days 1, 8 and V 100 mg PO QD of 21-day treatment cycles. Due to DLT reached in 2/3 patients in cohort 1 (one grade 3 and one grade 4 diarrhea/dehydration), 6 patients were treated then at dose level -1 (O 80 mg/m2 day 1, D 30 mg/m2 days 1,8, V 100 mg PO QD days 1-21). At dose level -1 no further DLTs were noted and the combination overall was well-tolerated with expected hematological toxicities and one grade 3 episode of anorexia noted and this dose was assessed as MTD and RP2D. All enrolled patients had adenocarcinoma histology. At dose level 1, 1/3 documented PR and 2SD and at dose level -1 2/6 SD and 1 documented CR was noted (the patient with CR completed 8 cycles of therapy and continues in CR on maintenance V). 3/6 had PD as best response at dose level -1. The median number of cycles received was 4 (range 2-8+). Conclusions: The MTD of the combination of oxaliplatin/docetaxel and vandetanib is O 80 mg/m2 day1, D 30 mg/m2 days 1,8 and V 100 mg PO QD and the DLT is gastrointestinal toxicity, such as diarrhea and concomitant dehydration. At this dose the regimen has manageable toxicity and shows promising activity in the management of advanced gastroesophageal carcinoma. This study was supported by an ISS research grant from Aventis and investigational drug by AstraZeneca.
Early response evaluation of therapy with AP23573 (an mTOR inhibitor) in sarcoma using [<sup>18</sup>F]2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan
Authors: K. K. Sankhala, S. P. Chawla, A. Iagaru, R. Dellamaggiora, V. Chua, S. Daly, C. L. Bedrosian, G. K. Edwards, S. Cohen, G. D. Demetri
Journal: Journal of Clinical Oncology (2005)

9028 Background: AP23573 (AP) is a non-prodrug rapamycin analog, which potently inhibits mTOR, a downstream effector of the PI3K/Akt pathway. AP has demonstrated some anti-tumor efficacy in sarcoma in phase I study. The relationship between mTOR and the glycolytic pathway provides mechanistic rationale for the use of PET as a non-invasive indicator of mTOR activity. Early response evaluation by PET was studied in this phase 2 trial in advanced sarcoma pts. Methods: AP is dosed at 12.5 mg IV daily X 5 days every 2 weeks (1 course). PET scan was done on D1 and D5 of the first course of AP using a CTI Viewer 16 PET/CT scanner with LSO crystals (11 pts) or a Siemens Biograph 2 PET/CT scanner with LSO crystals (14 pts). The five areas with highest FDG accumulation at baseline were selected as target lesions. Percent difference in sum of maximum standard uptake values (SUVmax) were compared for each patient on D1 and D5. These values represent a measure of FDG uptake. Response criteria used were recommended by the EORTC PET Study Group (Eur J Cancer. 1999; 35; 1773–1782). In the targeted lesions D5, SUVmax normalization was considered as complete metabolic response (CMR), while >25% SUVmax reduction was considered partial metabolic response (PMR). Stable metabolic response (SMR) was defined by an SUVmax change less then ±25% and increased metabolic response (IMR) was considered >25% increase in SUVmax. Further evaluation with PET scan is planned after 4 courses of AP. Results: 25 pts (14M/11F) were enrolled (age 18–76 yrs, median 57 yrs). Two pts showed no abnormal 18-FDG accumulation on D1, hence D5 PET was omitted. Of the remaining 23 pts, 9 pts (39%) showed PMR (SUV decreased by 25.3–58.7%). 14 pts (61%) had SMR (9 pts had SUV decrease by 4.7–21.6% and 5 pts had SUV increase by 0.7–5.5%). None of the patients had IMR or CMR. 5/9 pts with PET evidence of PMR showed clinical improvement as demonstrated by reduced symptoms of pain, shortness of breath and cough. Conclusions: This is the first known report of the use of PET to evaluate mTOR inhibition in non-GIST sarcomas. PET appears to be valuable in initial evaluation of patient response to treatment with AP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ariad Ariad Ariad
Phase 1/2 trial of MKC-1 and pemetrexed in patients (pts) with advanced NSCLC
Authors: T. Hoang, G. Clamon, H. West, A. Hannah, C. Sidor, S. Marcotte, D. Estes, J. Arnott, N. H. Hanna
Journal: Journal of Clinical Oncology (2008)

19052 Background: MKC-1 is a novel oral cell cycle inhibitor with in vitro and in vivo activity against many tumor cell lines, including NSCLC and multi-drug resistant cell lines and single agent activity in NSCLC patients. Binding targets of MKC-1 include microtubules and members of the importin-β family (involved in nuclear transport and spindle formation). Additionally, MKC-1 has been demonstrated to inhibit the Akt-mTOR pathway in vitro and in vivo. The objectives of this study are to define the Recommended Phase 2 Dose (RP2D) of MKC-1 in combination with pemetrexed and to determine the activity (progression free survival) of this combination in advanced NSCLC pts who have progressed following initial chemotherapy. Methods: Phase 1 dose escalation used 3+3 rules. MKC-1 is given orally at escalating doses twice daily for 14 days in combination with pemetrexed 500 mg/m2 on day 1 each 21 day cycle. Following 4 cycles of combined treatment, single agent MKC-1 is continued as maintenance therapy. An interim analysis will occur after 17 pts in phase 2 (1 objective response is required to proceed to the 2nd stage of accrual). Results: 19 pts have enrolled to date (8 in Phase 1 and 11 in Phase 2). Median age is 66. All pts were treated with prior platin-based chemotherapy. In phase 1 (n=8), all grade toxicities were fatigue (75%), anorexia (63%), nausea, vomiting, and dyspnea (all 50%), and neutropenia (25%). None of the 6 pts treated at dose level 1 (75 mg/m2 MKC-1) experienced DLTs. Both pts at dose level 2 (100 mg/m2) experienced DLTs: one had G4 neutropenia and G3 dehydration; the other had G4 neutropenia with G3 pneumonia, fatigue and thrombocytopenia. Dose level 1 was declared the RP2D. Of the 11 phase 2 pts, 7 were evaluable for tumor response and 3 are too-early-to-assess. One pt did not complete cycle 1. Best response to date is stable disease (SD), which was seen in 7 pts. Of note, 1 active pt (whose disease progressed after carboplatin/paclitaxel/bevacizumab and erlotinib) has stable disease for >8 months and still on MKC-1 monotherapy with minimal toxicity (mild fatigue). Conclusions: The RP2D of MKC-1 (75 mg/m2) and pemetrexed (500 mg/ m2) has been defined. The combination is well tolerated. Best response to date has been SD for >8 months. Phase 2 accrual continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration EntreMed EntreMed EntreMed EntreMed
Risk assessment for severe hypocalcemia requiring hospitalization with denosumab.
Authors: Karen A. Autio, Azeez Farooki, Ilya Glezerman, Amelia Chan, Hallie C. Barr, Brian M. Seyboth, Coursen Walker Schneider, Glenn Heller, Howard I. Scher, Michael J. Morris
Journal: Journal of Clinical Oncology (2013)

115 Background: Skeletal-related events (SRE) pose clinical risks to patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) that can be mitigated with denosumab. Hypocalcemia is a side effect, however risk factors are not well described. Methods: An IRB waiver was obtained to review medical records for all mCRPC pts receiving denosumab at MSKCC between March-August 2011 for baseline labs, calcium (ca) and vitamin D nadirs, details of hospitalizations, concurrent therapies, and comorbidities. Comparisons between groups were made using Fisher’s exact test and the Wilcox rank sum test. Results: Nine of sixty pts (15%) treated with 1-2 doses of denosumab developed severe symptomatic hypocalcemia (median nadir 6.5 mg/dL) requiring hospitalization for intravenous (IV) ca replacement. Ca/Vitamin D was recommended to all pts. Ca recovered in 17 days in those who did return to baseline levels (n=5). However, four of nine (44%) pts required repeated hospitalizations for IV ca, never recovered to baseline ca levels, and died of advanced disease within 3 months. Median vitamin D 25-OH was 22.5 ng/ml for hospitalized pts, and PTH was 198 pg/ml at ca nadir. Conclusions: Denosumab was associated with severe hypocalcemia sufficient to require hospitalizations for IV ca replacement in 15% of pts with mCRPC. PSA, Ca, Alk Phos, and current chemotherapy were associated with severe hypocalcemia requiring hospitalization for IV ca. Clinicians are cautioned regarding potential risk factors including advanced disease, vitamin D insufficiency, and possibly comorbidities affecting calcium absorption. [Table: see text]
Pilot study of target therapy with EGFR antibody (nimotuzumab) in patients with unresectable head and neck cancer.
Authors: W. Guo, G. Ren, C. LI, Y. WU
Journal: Journal of Clinical Oncology (2011)

e16008 Background: To explore the efficacy of the combination of biological target therapy and chemotherapy. Methods: Seventy-one patients (54 men and 17 women aged from 30 to 83 years; mean 60) with local advanced oral-maxillofacial & head and neck tumors (no indication for surgery, radiotherapy) confirmed by histology and radiology, having indication of bio-chemotherapy, were enrolled in this study. The chemotherapy regimen is CDDP 75mg/m2 d1,TAX 75mg/m2 d1, 5-Fu 750mg/ m2 d1-5 and Nimotuzumab 200mg/m2/w. Results: The patients completed chemotherapy 2 to 4 cycles, mean 2.2 cycles; Nimotuzumab were used 2 to 8 times, mean 4.3 times. The prognosis was as follows: CR 4 cases, PR 39 cases, SD 18 cases, PD 3 cases, and 7 cases cannot be evaluated. The total effective rate which was calculated by PR plus CR was 61%. Twenty-nine cases of them received surgery after bio-chemotherapy. No serious adverse reaction was found during the course of the treatment, only one case with slight erythra. Conclusions: Nimotuzumab was equally effective in the increase of chemosensitivity and good tolerability profiles.
A multivariate analysis of prognostic factors from assure (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma.
Authors: Naomi B. Haas, Judith Manola, Robert G. Uzzo, Keith Flaherty, Michael Pins, Edward M. Messing, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2016)

618 Background: Previous post-surgical prognostic nomograms for clear cell RCC are based upon TNM stage, PS, Fuhrman grade, and sometimes presence of necrosis. 1943 patients (pts) with locally advanced renal cell carcinoma (RCC) participated in the ASSURE trial of one year of sunitinib daily for 4 wks of a 6 wk cycle, sorafenib daily, or placebo, then treated for up to 9 cycles. Of these, 1541 pts had clear cell predominant features. There were no significant differences in DFS (median 5.7 years) between either of the experimental arms and placebo, in the total or clear cell population. We investigated site-reported clinical and surgical factors associated with prolonged DFS. Methods: Patients were staged according to the AJCC 2007 version. Factors considered in addition to those in the final model shown below were age, race/ethnicity, histology, risk category and PS as stratified, and 10 other specific baseline symptoms. A Cox proportional hazards model was built including factors that significantly changed the -2 log likelihood ratio (Collett). Results: Shorter DFS was associated with higher age, stage and Fuhrman grade, male sex, PS &gt; 0, open vs. laparoscopic surgical approach, low hemoglobin and diagnosis based on presence of symptoms. Conclusions: The association of stage, grade, age, and PS with outcome confirms previous analyses in resectable disease. The same factors which predict outcome in metastatic disease now clearly confer relapse risk in the postoperative setting. Clinical trial information: NCT00326898. [Table: see text]
Carboplatin and docetaxel as first-line chemotherapy in metastatic breast cancer patients. Preliminary results
Authors: M. E. Vassilomanolakis, G. Koumakis, V. Barbounis, S. Demiris, C. Panopoulos, S. Drufakou, A. Efremidis
Journal: Journal of Clinical Oncology (2005)

862 Background: To determine the efficacy and safety of a combination of Carboplatin and Docetaxel as first-line treatment in patients with metastatic breast cancer (MBC). Methods: eligibility criteria: no previous palliative chemotherapy; PS <3; bidimensionally measurable disease; adequate renal and hepatic function; age<73; Treatment consisted of Carboplatin AUC 5 and Docetaxel 75mg/m2 d1 every 3 wks. Twenty-five consecutive women with untreated MBC have entered the study until now and are eligible for evaluation. Results: Patients data: median age 59 yrs (range 36–73); Estrogen receptors positive 56%; median time from initial diagnosis to first relapse 13 months (range 0–180); previous adjuvant chemotherapy 52%; previous adjuvant hormonal therapy 56%; Disease sites: lung/pleura 52%; nodes/chest wall/breast 44%; liver 40%; >2 metastatic sites 60%; Results: Response: six pts (24%) achieved CR and 8 pts achieved PR (32%) for an overall response rate 56%; stable disease was observed in 8 (32%) pts; 3 pts had progressive disease(12%); median time of response 9(+) months. Toxicity: grade 3 /4 neutropenia 6 pts (24%); febrile neutropenia requiring hospitalization occurred in 1 pt; mild anemia 7 pts (28%); stomatitis grade1 one patient; diarrhea grade3 /4 two patients; alopecia was common; there was no toxic death. Conclusions: our first results suggest that Carboplatin/Docetaxel combination is a safe and active regimen for first line metastatic breast cancer treatment. No significant financial relationships to disclose.
Efficacy of Gemtuzumab Ozogamicin (GO) Monotherapy on Relapsed/Refractory Acute Promyelocytic Leukemia (APL)
Authors: Akihiro Takeshita, Takaaki Ono, Yumi Kojima, Taiichi Kyo, Norio Asou, Hitoshi Suzushima, Fumiharu Yagasaki, Tomoya Maeda, Masaya Okada, Chiaki Nakaseko, Hiroyuki Kanbayashi, Masaki Yamaguchi, Mitsutoshi Kurosawa, Kosuke Tsuboi, Toshiaki Yujiri, Yasuhito Nannya, Naokuni Uike, Nobu Akiyama, Tetsuya Fukuda, Kaori Karimata, Hirokazu Okumura, Tetsuya Eto, Koh Izumiyama, Akihiro Watanabe, Nobuyuki Aotsuka, Katsuro Ito, Keiji Ozaki, Tomoki Naoe
Journal: Blood (2011)
Emergency department (ED) utilization and hospital admission rates among oncology patients at a large academic center and the need for improved urgent care access.
Authors: Kerin B. Adelson, Vanna Dest, Salimah Velji, Richard Lisitano, Rogerio Lilenbaum
Journal: Journal of Clinical Oncology (2014)

19 Background: In the US, 30% of the total cancer expenditure is spent in the last year of life and 55% of this is spent on inpatient care. For patients with advanced cancer, most hospitalizations arise from expected disease progression. With the ultimate goal reducing hospital admissions at the Smilow Cancer Hospital at Yale New Haven, we sought to understand our patterns of ED referral, hospital admission, and length-of-stay. Methods: An analysis of all oncology patients coming to the Yale New Haven Hospital (YNHH) ED was performed by executing reports through our EPIC electronic medical record. We looked at a 5-month time frame from January 1, 2014, through May 31, 2014. Results: A total of 391 oncology patients from each of our disease groups presented to the ED and 90% were admitted. Mean length of stay (LOS) was 6.74 days. 62% of patients arrived during the hours of 9:00AM-5:00PM. The average daily cost per admission was $1886 per day/ $12,711.64 for the mean hospitalization (largely spent on nursing, pharmacy, and laboratory). At least 50% of these presentations could have been addressed in the ambulatory setting including but not limited to dehydration, abdominal pain and failure-to-thrive. Conclusions: Despite a 6-day/wk ambulatory oncology practice, our patients are presenting to the ED during standard daytime hours resulting in admission and prolonged length-of-stay. We will launch a same-day visit program with access to urgent palliative care consultation, pharmacy and infusion chairs. We will treat dehydration, nausea, vomiting, pain, DVT, and other urgent presentations. This cultural change will require education of physicians, nurses, staff, patients and caregivers. We estimate that a 50% reduction in admissions would yield a cost savings of approximately $6 million annually. [Table: see text]
Study to assess satisfaction of general practitioners (GP) with oncology services, GP awareness of follow-up guidelines for patients with cancer, and GP access to oncology services.
Authors: A. M. Noonan, D. N. Carney, J. McCaffrey
Journal: Journal of Clinical Oncology (2011)

e19643 Background: The Irish National Cancer Control Programme Performance Monitoring Report published in December 2008 proposed the development of community oncology care led by general paractitioners (GPs) including long-term follow-up for well patients. Methods: A printed questionnaire was mailed to 198 general practitioners in the North Dublin area seeking to answer 5 main points: (i) adequacy of information relayed to GPs regarding treatment plan and potential side effects of cancer treatments, (ii) GP awareness of follow-up guidelines for patients treated with curative intent for breast, colon and testicular cancer, (iii) GP ease of access to radiological examinations, (iv) GP access to palliative care services, (v) degree of GP confidence in following up oncology patients discharged to their care. Results: 115 questionnaires were returned. Overall response rate (49%) was calculated using 97 fully or partly completed questionnaires. 69% of GPs felt that they did not receive adequate information regarding the treatment plan. Regarding access to the parent hemtology/oncology team, 53% of GPs reported that they had some difficulty, 27% could easily contact the team, 7% reported that they had major difficulty and only 8% could very easily contact the team. The table illustrates the public healthcare access GPs have to radiological investigations. Only 36% (35/97) of GPs were aware of follow-up guidelines for early breast and colon cancer and only 25% were aware of the follow-up guidelines for testicular cancer. 88% of GPs have access to palliative care services and 16% of GPs have formal training in palliative care. 50% of GPs felt confident about following up well cancer patients in the community. Conclusions: GP-led community oncology follow-up of well patients will require increased GP access to radiological investigations and improved communication between parent oncology teams and GPs. Radiologic investigation Access directly (%) Access directly but waiting time >4 weeks (%) Requires hospital referral (%) Not answered (%) Dexa scan 41 33 21 3 Mammography 31 31 30 5 Ultrasound 27 52 15 3 CT scan 14 7 72 4 MRI scan 13 6 72 6 PET scan 2 2 83 10