tbuckley/cabot-search huggingface dataset:
Day 1 pegfilgrastim with dose dense adjuvant chemotherapy: Amelioration of docetaxel neutropenia but not that of doxorubicin/cyclophosphamide. Results from a Sarah Cannon Research Institute pilot study
Authors: D. A. Yardley, F. A. Greco, H. A. Burris, N. W. Peacock, M. White, E. Raefsky, D. S. Thompson, J. H. Barton, D. R. Spigel, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2005)

749 Background: Dose dense chemotherapy, achieved by shortening treatment intervals, has resulted in improved DFS and OS for doxorubicin/cyclophosphamide (AC)→ paclitaxel although with a higher incidence of toxicity, costs, & cytokine support. This pilot evaluates the feasibility and toxicity of dose dense docetaxel (D)→ AC as adjuvant or neoadjuvant therapy, with this sequence selected to minimize the palmar-plantar erythema (PPE) noted with D following anthracyclines. Same day pegfilgrastim (P) was administered for pt convenience. Methods: Eligibility: locally advanced, LN + or high risk LN neg pts (T > 2 cm or T ≥ 1 cm with either: ER/PR neg, GIII histology, age < 35), PS 0–1, normal LVEF, adequate organ function with no metastatic disease. Treatment was D 100 mg/m2 followed by AC (60/600 mg/m2), each for 4 cycles at q14d intervals with P 6 mg sc D1 x 8 cycles. Results: Between 3/4/04 & 7/28/04, 33 pts with median age 52 were enrolled. 31 pts were treated adjuvantly & 2 neoadjuvantly. 23 tumors were LN +, 8 LN neg, 12 ER/PR +, and 21 ER/PR neg. 33 pts are evaluable for toxicity with 27 pts completing all 8 cycles. 132 D and 113 AC cycles have been administered to date. G 3/4 heme toxicity for D was modest & notable only for anemia in 2 pts compared to 5 pts with AC. Despite P, 24 AC pts experienced G 3/4 neutropenia, 3 with fever. G 3/4 non-heme toxicity for D was remarkable for arthralgias-7, PPE-2, & fatigue-2 pts while for AC, fatigue-6pts and N,V-1 pt were the most prominent. Dose reductions occurred in 12 pts; 3 D pts for G3-PPE, G3-neuropathy, G3-fatigue and 9 AC pts due to G 3/4 neutropenia-6 & febrile neutropenia-3 pts. 4 pts required PRBCs with AC. Conclusion: With this sequence and D schedule, PPE was minimal (2pts). Same day P ameliorated D’s myelosuppression but did not impact on the G 3/4 neutropenia seen with AC, perhaps even contributing to it. The higher than expected incidence of G 3/4 arthralgias with D may be due to P, while the sequence or P may have contributed to the significant G 3/4 heme toxicity with AC. Dose dense docetaxel followed by AC is safe and feasible; standard day 2 pegfilgrastim dosing may be preferable, particularly with AC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis
Influence of obstructive jaundice on chemotherapy in patients with unresectable biliary tract cancer.
Authors: Satoshi Shimizu, Shuichi Mitsunaga, Izumi Ohno, Hideaki Takahashi, Hiroyuki Okuyama, Akiko Kuwahara, Takuji Okusaka, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2014)

336 Background: The aim of this study was to investigate the influences of obstructive jaundice (OJ) in unresectable biliary tract cancer (BTC) patients. Methods: Data of a total of 200 patients who were newly diagnosed as having unresectable BTC and received chemotherapy between July 2006 and December 2012 were retrospectively reviewed. Patients were divided into two groups according to whether or not they presented with OJ as the incipient chief complaint (Group 1, patients with OJ; Group 2, patients without OJ). Results: There were 81 patients in Group 1 and 119 patients in Group 2. In regard to the primary site (Group 1/Group 2), 29 had perihilar (27/2), 7 had distal (7/0), 68 had intrahepatic (15/53), 92 had gallbladder (31/61) and 4 had ampulla of vater (1/3) (p&lt;0.01). The rate of distant metastasis was 60% in Group 1 and 76% in Group 2 (p=0.02). The performance status was good (0 or 1) in 96% of cases of both the groups. There were no significant differences in the median survival time between Group 1 and Group 2 (9.0 months vs. 9.0 months, p=0.42) or in the progression free survival of 1st line chemotherapy between the two groups (4.1 months vs. 3.7 months, p=0.08). The rate of development of biliary obstruction in Group 1 was significantly high during the first line chemotherapy (56% vs. 10%, p&lt;0.01). Discontinuation of 1st line chemotherapy was necessitated due to biliary obstruction in 9 patients (10%) of Group 1 and none of the patients (0%) of Group 2. Multivariate analysis showed that absence of metastasis and use of a doublet chemotherapy regimen were significantly correlated with the overall survival, but not the presence of OJ as the incipient chief complaint (HR, 0.772; 95% CI, 0.532-1.119). Conclusions: Patients with OJ as the incipient chief complaint showed high rate of recurrent biliary obstruction and discontinuation chemotherapy due to biliary obstruction. However, OJ may not disadvantage for overall survival in BTC.
Predictors of failure to perform pelvic peritoneal cytology in endometrial cancer staging surgery.
Authors: Micael Lopez-Acevedo, Chelsea Zhang, Angeles Alvarez Secord, Paula S. Lee, Laura Jean Havrilesky, Andrew Berchuck
Journal: Journal of Clinical Oncology (2012)

201 Background: The Federation of Gynecology and Obstetrics (FIGO) staging system and the National Comprehensive Cancer Network (NCCN) guidelines for endometrial cancer recommend performing pelvic peritoneal cytology to look for the presence of cancer cells in the peritoneal cavity in patients who are undergoing surgical staging of apparent non-metastatic disease. About 10% of cases have positive cytology and this information is used in formulating plans for adjuvant therapy. However, adherence to the guidelines recommending that cytology be performed is not universal. In this study, we sought to identify factors associated with failure to perform pelvic peritoneal cytology at the time of endometrial cancer staging surgery. Methods: We performed a retrospective study of women with FIGO stage I/II endometrial adenocarcinoma who underwent endometrial cancer staging surgery at our institution from 1993-2007. Predictors of failure to perform cytology that were investigated included: surgeon, presence of adhesions, intraoperative blood loss and conversion from laparoscopy to laparotomy. Results: Among 1,112 cases, peritoneal cytology was not performed in 76 (6.8%). In 30 cases cytology was not performed for valid reasons including 15 in which the surgery was performed vaginally, 10 in which the diagnosis of endometrial cancer was not known prior to surgery and 5 in which gross evidence of stage III/IV disease was found at surgery. Of the remaining 46 cases, 11 (23.9%) had surgery that was converted from laparoscopy to laparotomy, 16 (34.8%) had dense pelvic adhesions and 40 (87.0%) had an estimated blood loss greater than 100 ml. The frequency of these and other risk factors will be compared to that seen in a matched cohort of patients who did have pelvic peritoneal cytology performed. Conclusions: Our analysis will investigate predictors of failure to perform pelvic peritoneal cytology. Increased awareness of these factors has the potential to improve compliance with this accepted procedure that plays a role in planning adjuvant therapy for early stage endometrial cancer.
Avoidable and unavoidable visits to the emergency department among advanced cancer patients (AdCa) followed by the supportive care (SCPC) outpatient clinic.
Authors: Marvin Omar Delgado-Guay, SeongHoon Shin, Gary B. Chisholm, Janet L. Williams, Julio Allo, Eduardo Bruera
Journal: Journal of Clinical Oncology (2013)

140 Background: Admissions to ED are considered undesirable for AdCa receiving palliative care. There is limited research about clinical characteristics of AdCa followed by SCPC who visited ED, and if these ED visits can be categorized as avoidable or unavoidable. Methods: Retrospective study of 200 consecutive AdCa evaluated by the SCPC physician who visited ED between January 2010 and December 2011. All patients were instructed to call to our main number if any change in symptoms. Based on pre-defined criteria AdCa were classified as having an avoidable (if the problem could have been managed at the outpatient center or by telephone) or unavoidable visit. Demographics and clinical characteristics were collected and analyzed. Results: 47/200 (23.5%) AdCa had avoidable ED-visits (AvED) and 153/200 (76.5%) had unavoidable ED-visits (NAvED). Main reasons for NAvED: changes in mental statu s(24/153, 16%), infectious processes (32/153, 21%), new onset/worsening of pain and dyspnea (75/153,49%), and severe worsening others symptoms (22/153,14%). Age, gender, marital status, and cancer types, reasons for referral to SCPC, and time to ED-visit after SCPC visit were not significantly different between AvED and NAvED patients. Baseline Edmonton Symptom Assessment Scale showed no significant difference in pain, dyspnea, fatigue, drowsiness, nausea, well-being, anxiety, and depression for AvED vs. NAvED; except for sleep ≥1: 141/153 (92%) vs. 37/47 (79%), p=0.01001, respectively. None of the patients phoned the SCPC before to ED visit. 17/153 (11%) of AdCa called their primary oncology before NAvED visit vs. 1/46(2%) call before AvED, p=0.078. Multivariate analysis showed that NAvED was associated with worsening of pain (OR:2.485, p&lt;0.0179), changes in mental status (OR:23.143, p&lt;0.0098), and sleep disturbance(OR:3.611, p&lt;0.0116). 0/47(0%) AvED vs. 93/153 (51%) of NAvED were admitted to the hospital, p&lt;0.0001. Conclusions: More than one in five of ED visits by AdCa are avoidable. Efforts through to improve communication after the scheduled appointments, through clinician initiated phone calls, electronic communication and more frequent visits are needed.
Driving action through data: Delivering online cancer screening reports to primary care providers.
Authors: Nicki Cunningham, Shama Umar, Dafna Carr, Richard Smith, Patrick Flynn
Journal: Journal of Clinical Oncology (2014)

174 Background: The Screening Activity Report (SAR), a supplementary tool for primary care providers (PCPs), was released in April, 2014. Providers are able to access this comprehensive report securely via an online solution and view the screening activity of their patients across Cancer Care Ontario (CCO)’s three organized cancer screening programs; breast, cervical and colorectal. The objectives of the SAR are to improve the quality of cancer screening by increasing provincial screening rates, improving the rate of appropriate follow-up of abnormal results and promote the alignment of cancer screening practices with CCO’s evidence-based clinical guidelines. Methods: CCO partnered with eHealth Ontario in 2012 to leverage their identity and access management system to provide safe and secure online access to the report. Since this time, CCO has implemented a multi-faceted campaign to support registrations to the system, encourage report access, and gather feedback on how to improve the report for future iterations. Using a detailed methodology developed by a wide range of subject matter experts at CCO, the SAR employs numerous provincial data sources to provide an overview of the patient rosters. Actionable categories are assigned at the patient level using a unique algorithm based on the latest clinical guidelines. Results: Previous to April 2014, the SAR was referred to as the ColonCancerCheck SAR (CCC SAR) as it included colorectal cancer screening data only. The last release of the CCC SAR was in October, 2013. At this time 4,824 providers were registered to the identity and access management system and adoption of this report had reached 31% after being available for five months to providers. To date, 4,992 providers are now registered and adoption of the April SAR has already reached 27% after being available for almost two months. Conclusions: The SAR is the first tool of its kind to make widespread use of eHealth’s identity and access management system service and target a broad user base of PCPs. The successful launch of the SAR has provided key insights into how technology can be leveraged to share provincial data in a meaningful way with providers and support them in improving the quality of cancer screening.
Examining the reliability of surrogate tissue predictability of drug efficacy in reconstituted human 3D skin models containing melanomas.
Authors: Palak R. Parekh, Christophe E. Redon, Urbain Weyemi, William Bonner
Journal: Journal of Clinical Oncology (2012)

49 Background: Melanoma has a poor survival rate in advanced stages due to the lack of efficacious approved treatments. However, melanoma’s dermal location enables the application of human skin models. These models mimic many important characteristics of skin in vivo and obviate the use of invasive procedures. Monitoring gamma-H2AX foci to assess DNA double-strand break (DSB) levels in reconstituted human 3D skin tissue harboring melanoma tumor cells may provide insights into important questions in cancer research. In addition to the differential toxicities of anti-cancer agents on the various cell types, we examine how the early drug response of normal tissues might serve as surrogates for predicting treatment efficacy on the tumors. Methods: Commercially available reconstituted 3D human skin tissue consists of dermal fibroblast and epidermal keratinocyte layers with malignant melanoma A375 cells which have been cultured to form a multilayer, highly differentiated epidermis containing various stages of cutaneous melanoma malignancy. Drugs representative of several different categories were studied, including bleomycin (a radiomimetic), camptothecin (a topoisomerase I inhibitor), temozolomide (a DNA alkylating agent), AZD6244 (a MEK inhibitor), Vorinostat (a HDAC inhibitor) and cisplatin (a DNA intercalatingagent). DNA DSB levels were monitored by gamma-H2AX foci formation and apoptosis by TUNEL assay. Tumor growth was monitored by H&amp;E staining. Results: A wide range of responses in both tumor and normal tissue by various drugs were observed, including tumor regression and normal tissue toxicity. The early responses of normal tissues depended on the treatment, providing insights into the use of surrogate tissues as predictors of drug efficacy and later tumor regression. Conclusions: Measuring DNA DSB damage in reconstituted 3D skin tissue is an attractive model for studying the efficacy and toxicity of genotoxic drugs against melanoma. If validated, such models would help reduce the use of animals for preclinical studies.
Determining the need and utilization of radiotherapy in cancers of the breast, cervix, lung, prostate, and rectum in Alberta, Canada.
Authors: Lorraine Shack, Shuang Lu, Lee-Anne Weeks, Peter S. Craighead, Marc Kerba
Journal: Journal of Clinical Oncology (2013)

116 Background: Determining the appropriate rate of RT is important for health care planning and resource allocation. Establishing RT shortfalls (difference between observed and estimates of RT need) could provide an estimate of the capacity expansion that would be required to address them. Our primary objective was to determine the utilization of RT for cancers of the breast, cervix, lung, prostate and rectum in Alberta (AB), Canada. To determine the burden of RT shortfalls in AB, the secondary objective was to compare the observed AB RT rates to estimates of need derived from criterion-based benchmarking (CBB) and evidence-based estimates (EBEST). Methods: All incident cases of breast (B), cervix (C), lung (L), prostate (P) and rectal (R) cancers diagnosed in 2004-8 in AB were identified from the provincial cancer registry (ACR). Ethics board approval was obtained. Patients receiving RT within one year (RT-1y) of diagnosis were identified and grouped by cancer site. The proportion of cases receiving RT-1y was then calculated. Rates were compared using a Z statistic of the normal approximation for a difference in proportions. Estimates of the appropriate RT rate were derived from CBB and EBEST methods described in the literature. Results: A total of 68,164 cancer cases of interest were identified from the ACR. RT-1y rates for AB (95%CI) were: B: 50.5%(49.5-51.4), C: 45.7%(42.2-49.3), L: 36.5%(35.5-37.3), P:26.4%(25.6-27.3) and R:38.8%(37.1-40.6). Observed rates of RT in AB were lower than estimates derived using CBB and EBEST of RT-1y for B: 60.7%(59.3-62.1) and 57.1%(52.6-62.0), C: 48.6%(39.1-58.1) and 63.4%(61.1-65.7), L: 41.3%(39.9-42.7) and 44.6%(41.0-48.2), P: 37.2%(35.8-38.7) and 32.0%(28.4-36.0), and R: 43.4%(39.1-47.6) and 69.6%(68.7-70.5). Shortfalls varied across cancer sites according to whether CBB or EBEST estimates were referenced, ranging from 4.8% in lung cancer to 30.8% in rectal cancer. Conclusions: Important shortfalls exist in the utilization of RT in Alberta, Canada despite centralized cancer care and a publically funded health care system. The magnitude of the shortfall varied according to whether a CBB or EBEST estimate of RT was applied.
Systematic pelvic and para-aortic lymphadenectomy for surgical staging of high-risk endometrioid adenocarcinoma of the endometrium: Indian experience.
Authors: S. Somashekhar, Z. Ahmed, S. S. Zaveri, S. Holla
Journal: Journal of Clinical Oncology (2011)

e15513 Background: The trend towards greater use of complete surgical staging in endometrial carcinoma has been accompanied by a marked decrease in the use of pelvic radiotherapy. Comprehensive surgical staging determines the subset of patients in whom pelvic and para-aortic radiation therapy is beneficial. We analyzed the results of pelvic and para-aortic lymphadenectomy in patients with high-risk endometrioid adenocarcinoma of the endometrium. Methods: Prospective non-randomized study, from April 2005 to April 2009, in endometrioid adenocarcinoma patients undergoing systematic pelvic and para-aortic lymphadenectomy. Results: Of the 76 patients who were operated, 48 patients underwent pelvic and para aortic lymphadenectomy. 14 (29.1%) patients had LVSI, 10 (20.8%) had FIGO G3 and elevated CA 125 levels. Mean number of nodes examined were 18 and 14 for pelvic and para-aortic lymphadenectomy respectively. Median time for para-aortic lymphadenectomy was 35 minutes and average blood loss was 30ml. 8.3% patients had pelvic, 4.1% had para-aortic and 16.6 % had both pelvic and para-aortic nodal involvement. Most frequently involved para-aortic nodes were above the origin of inferior mesenteric artery. Patients with LVSI had a 48% risk of nodal involvement. The risk factors for para-aortic nodal metastases were positive pelvic nodes, FIGO grade 3, LVSI and elevated CA-125 levels. There were no major complications. Paralytic ileus and lower limb lymphedema was seen in 7% and 2 % respectively. Conclusions: Over two thirds of patients with positive pelvic nodes had para aortic nodal involvement and 4% of patients had isolated para-aortic nodal involvement. The most common positive para-aortic nodes were at the junction of renal vein and IVC on left side and at the point of entry of right ovarian vein to IVC on the right side. Commonest Positive Para-aortic nodes were the one above IMA between renal veins and IMA. We recommend systematic para-aortic lymphadenectomy in high risk endometrioid adenocarcinoma patients. It can be done with minimal morbidity and gives a good loco-regional control.
Prospective analysis of chemotherapy-induced neuropathy in patients with gynecologic malignancies.
Authors: G. Riebandt, K. J. Rodabaugh, J. Pietkiewicz, M. K. Fong, A. E. Groman, S. B. Lele, K. Odunsi, S. Akers
Journal: Journal of Clinical Oncology (2011)

e19737 Background: Chemotherapy induced peripheral neuropathy (PN) is a serious dose- limiting toxicity affecting chemotherapy administration. It is unclear how many patients are assessed for PN. The incidence and severity of PN depend on the chemotherapeutic agents, cumulative dose, schedule and patient characteristics. Taxanes and platinum analogs are associated with the highest incidence of PN. Few tools have been validated to assess the incidence and severity of PN. The NCI Common Toxicity criteria (NCI-CTCAE), Patient Neurotoxicity Questionnaire (PNQ), and Functional Assessment of Cancer Therapy Neurotoxicity Subscale (FACT-Ntx) are the most studied. The primary objective of our study was the prospective evaluation of the incidence of severe PN (NCI-CTCAE≥2) in patients with gynecologic malignancy receiving taxane/platinum regimen. The secondary endpoint was to determine the questionnaire that was the most sensitive in predicting PN; NCI-CTCAE and PNQ. Methods: Fifty-one patients with ovarian or endometrial cancer receiving carboplatin-paclitaxel based chemotherapy were enrolled and 451 assessments were completed. Assessments were performed at baseline, chemotherapy visists and monthly follow ups. Results: Seventeen patients had baseline PN and 29 (85.3%) patients developed PN during treatment. The table depicts the mean cumulative doses for both agents and both tools. Conclusions: The incidence of carboplatin-induced PN has been reported to range from 13% to 42% and the reported incidence of paclitaxel induced PN varied from 18% to 29% (every 3 weeks dosing, mean cumulative dose to onset of grade ≥ 2 PN-715 mg/m2). We report the incidence of severe PN in 85.3% of patients receiving combination of carboplatin/paclitaxel. These preliminary results show trend for PNQ tool to detect both sensory and motor PN at lower mean cumulative doses when compared to NCI-CTCAE. Our higher incidence of PN than previously reported for carboplatin/paclitaxel demonstrated a need for standarization of detection and treatment of PN. Tool No. of Patients (%) Paclitaxel (mg) Carboplatin (mg) NCI-CTCAE sensory 20 (58.8) 1,138 1,907 NCI-CTCAE motor 16 (47.1) 1,142 1,810 PNQ sensory 18 (52.9) 818 1,383 PNQ motor 18 (52.9) 1,003 1,588
The dynamic CT perfusion evaluation of dual-route administration of the gemcitabine and cis-platinum regimen with Endostar for advanced non-small cell lung cancer.
Authors: J. Xu
Journal: Journal of Clinical Oncology (2011)

e17535 Background: The purpose of this study was to validate the clinical efficacy of dual-route administration of gemcitabine, cis-platinum and Endostar with functional dynamic CT perfusion imaging. Methods: 20 pathologically confirmed patients received the transarterial chemotherapy of gemcitabine (1000mg/m2) and cis-platinum (50mg/m2) together with Endostar (30mg), in the 1st day of a treatment cycle (four weeks as a unit cycle ). Next, in the 8th day of the cycle, another gemicitabine (1000mg/m2) was administrated through the venous pathway. In addition to above treatments, through the 2rd to 12th day of the treatment period, Endostar was treated with 15mg/d in a systemic venous way. The dynamic CT perfusion was carried out in the clinical experimental entry and in the last week of each treatment cycle, then the parameters of maximum diameter (Dmax), blood flow (BF), blood volume (BV) and permeability surface (PS) were calculated and statistically analyzed. Among of which, The maximum diameter represents the anatomic change, while the perfusion parametric quantities reflex the functional alteration. Results: Dmax before and in the first 3 cure periods is 6.40±2.41cm,5.29±2.09cm,4.53±1.85cm and 4.10±2.10cm; accordingly, BF is65.11±34.42ml·100ml-1·min-1A48.58±32.24ml·100ml-1·min-1A38.50±32.69ml·100ml-1·min-1 and 32.06±30.13ml·100ml-1·min-1; BV is 84.38±40.27ml·100ml-1A69.38±41.88ml·100ml-1, 50.07±30.39ml·100ml-1, 47.24±35.72ml·100ml-1; and Ps is 64.04±27.28ml·100ml-1·min-1A62.59±50.55ml·100ml-1·min-1A49.18±31.53ml·100ml-1·min-1 and 46.66±30.49ml·100ml-1·min-1, respectively; Friedman test was taken into use to compare the difference in each parameter, and Statistical diversity exited in all the above parameters, which show an antitumor effect not only in morphology, also in functional aspect. Conclusions: Dual-route administration of GP regime with Endostar could exert an antitumor and anti-angiogenetic effect for advanced NSCLC, which could be an optional choice in clinical experience.