tbuckley/cabot-search huggingface dataset:
ICU deaths in patients with advanced cancer: Criteria to decrease potentially inappropriate admissions and analysis of advance planning discussions.
Authors: Syed Sameer Nasir, Alva B Weir
Journal: Journal of Clinical Oncology (2016)

47 Background: A significant number of advanced cancer admissions to intensive care unit (ICU) are inappropriate, as they do not prolonged survival. No clear consensus criteria for reasonable admissions of advanced cancer patients have been developed. Methods: We established four criteria for ICU admissions in advanced cancer patients: post procedure complication, recent cancer diagnosis, good performance status and life expectancy of &gt; 6 months. We reviewed charts of all patients who died in the ICU at a university-affiliated hospital between 2005-2010. We then identified advanced cancer patients and looked for presence or absence of these criteria. We also reviewed evidence of advance planning discussions (APDs), prior to ICU admission to evaluate their benefit in preventing inappropriate admissions. Results: 421 deaths occurred in ICU between 2005-2010. 52 patients had advanced cancer. 27% were diagnosed with cancer one month or less prior to admission. 40% had ECOG performance status of 0-1. 27% had life expectancy of more than 6 months and 15% were admitted for post procedure complications. Overall, 37% did not satisfy any of our reasonable criteria at the time of ICU admission. In our chart review for evidence of APDs, 31% had completed APDs prior to ICU admission. 47% of patients who did not satisfy any of our reasonable admission criteria had APDs indicating desire for limited medical intervention. Patients lacking both reasonable admission criteria and APDs were 15%. Conclusions: Incorporating proposed admission criteria in ICU admission guidelines may prevent significant number of inappropriate, advanced cancer admissions to the ICU, thus avoiding ineffective, aggressive interventions and delay in timely access to high-quality hospice and palliative care. Our data confirms other data in suggesting that a simple increase in numbers of APDs would not likely change significantly the numbers of inappropriate ICU admissions. [Table: see text]
Patterns of recurrence after resection of rectal gastrointestinal stromal tumors and the effect of adjuvant therapy.
Authors: Masayoshi Yasui, Masaki Mori, Tsuyoshi Takahashi, Yasuo Nakashima, Tsutomu Dousei, Yoshito Yamashita, Junya Fujita, Masako Hiramatsu, Ryohei Kawabata, Koji Nakai, Takuya Nakai, Toshirou Nishida, Miki Noguchi, Hajime Orita, Yoshiharu Shono, Yoshihito Souma, Masakazu Takagi, Shugo Ueda, Kazuyoshi Yamamoto, Toshimasa Tsujinaka
Journal: Journal of Clinical Oncology (2013)

531 Background: Since gastrointestinal stromal tumors (GISTs) of the rectum are rare, clinical features and treatment outcome have not been well documented. Methods: Data from patients with rectal GIST diagnosed and primarily treated between 2003-2007 at 17 institutions in Japan were collected and analyzed on clinical characteristics, pathologic features and recurrence patterns. Results: Twenty-five patients (11 men and 14 women) with rectal GISTs were collected. Median age was 67years old. Pathological examinations disclosed that the median number of mitoses and the size of tumors were 4 counts/50HPF and 4.5cm, respectively. By the Miettinen criteria, 44 percent (n = 11) were classified as high-risk, 32 percent (n = 8) as low-risk and 16 percent (n = 4) as none-risk gastrointestinal stromal tumors. Sixty-three percent (7/11) of patients with high-risk GISTs had developed recurrence. None of patients (n = 12) with low or none-risk gastrointestinal stromal tumors have recurred after a median follow-up of 1699 (range, 135-3871) days. 85 percent (6/7) of recurrent patients showed loco-regional recurrence. Twelve patients with rectal GISTs received local excision and thirteen patients received extended resection (abdominoperineal resection or low anterior resection). Loco-regional recurrence rate following local excision was 25% (3/12), which was similar with that of extended resection (23%, 3/13).7 patients received neoadjuvant and/or adjuvant imatinib. Only one patient of 7 patients who received perioperative imatinib treatment developed recurrence. Conclusions: Loco-regional recurrence was the most predominant pattern of recurrence after surgical resection of rectal GISTs. The Miettinen criteria were useful to differentiate the high risk group. Recurrence rate was lower in patients treated with perioperative imatinib. Rectal GIST may be optimally managed by perioperative multimodal treatment instead of extending surgical resection.
Cbl Mutants Interact with c-Kit and Lead to Factor Independent Growth and Transformation of a Myeloid Cell Line 32D.
Authors: Bülent Sargin, Srinivasa Rao Bandi, Benjamin August, Marion Rensinghoff, Chunaram Choudhary, Pavan Nagaruri Gonchi, Wolfgang E. Berdel, Carsten Müller-Tidow, Hubert Serve
Journal: Blood (2007)
Sunitinib as first-line therapy in elderly patients (age 70 and older) with metastatic renal cell cancer.
Authors: Ugo De Giorgi, Karim Rihawi, Giovanni Lo Re, Teodoro Sava, Cristina Masini, Michele Aieta, Andrea Camerini, Giuseppe Fornarini, Luciano Burattini, Fabio De Vincenzo, Giovanni Rosti, Vittorio D. Ferrari, Luca Moscetti, Vincenzo Emanuele Chiuri, Stefano Luzi Fedeli, Emanuela Scarpi, Umberto Basso
Journal: Journal of Clinical Oncology (2012)

411 Background: Many medical oncologists are still reluctant to use the standard sunitinib regimen in older patients (pts) with metastatic renal cell cancer (mRCC) because of concerns about tolerance. We assessed the routine use of first-line sunitinib in mRCC pts aged ≥70 yrs. Methods: We reviewed the clinical files of 154 pts aged ≥70 yrs with mRCC treated with first-line sunitinib in sixteen Italian Oncology Units from February 2006 to April 2011. Sunitinib 50 mg/d 4 wk on/2 wk off was considered the standard regimen (SR). All alternative schedules of sunitinib administration were considered as adapted regimens (AR). After univariate analysis a multivariate analysis was carried out by Cox regression model and included the following variables: age (&lt;75 vs ≥75 yrs), Eastern Cooperative Oncology Group (ECOG) performance status (PS; 0-1 vs ≥2), presence of comorbidities (0 vs ≥1), lymphocytopenia (&lt;1,000/microL vs &gt;1,000/microL), prognostic score for VEGF-targeted agents according to Heng 2009 (good + intermediate prognosis vs poor prognosis), and treatment schedule (SR vs AR). Results: Median age was 74 yrs (range, 70-88 yrs). One hundred six pts (68.8%) received a SR and 48 (31.2%) received an AR consisting of 37.5 mg/d 4 wk on/2 wk off (32 cases, 67%), 25 mg/d 4 wk on/2 wk off (12 cases, 25%) and 37.5 mg continuous once-daily dosing in (4 cases, 8%). Pts treated with an AR were older than those treated with the SR (≥75 yrs, 56% vs 32%, respectively, p=0.008); with no differences for the other variables. Pts received a median of 4 sunitinib cycles with either SR or AR. Grade 3-4 toxicities occurred in 65% of SR and 42% of AR (p=0.008); dose reductions were required in 64% and 40%, respectively (p=0.005); discontinuations due to therapy-related adverse events occurred in 23% and 21%, respectively (p=0.967). Median progression-free survival (PFS) was 10.6 months (95% CI 8.7-15.3) and median overall survival (OS) was 20.1 months (95% CI 15.5-not reached). In multivariate analysis, only PS and the Heng score were predictors of either PFS or OS. Conclusions: Sunitinib is active and feasible in pts with mRCC aged ≥70 yrs. AR does not appear to influence PFS and OS and has a favorable impact on toxicity.
The effect of pain on survival in non-small cell lung cancer (NSCLC) patients with bone metastases receiving chemotherapy
Authors: K. Yoh, K. Kubota, H. Ohmatsu, K. Goto, S. Niho, Y. Nishiwaki, N. Saijo
Journal: Journal of Clinical Oncology (2008)

20666 Background: Bone metastases cause pain and considerable skeletal complications, and complicate the clinical course in patients with advanced solid tumors. Few data are limited concerning the incidence of skeletal-related events (SREs) and prognosis in non-small cell lung cancer (NSCLC) patients with bone metastases receiving chemotherapy. The purpose of this study was to identify detailed clinical course in NSCLC patients with bone metastases receiving 1st-line chemotherapy. Methods: Retrospective analysis of advanced NSCLC patients who were treated at our institution between 2002 and 2004 was performed using medical records. Patients who had bone metastases at the time of beginning 1st-line chemotherapy were included in the study. SREs were defined as pathologic fractures, spinal cord compression, surgery to bone, and radiotherapy to bone. Results: A total of 114 consecutive NSCLC patients with bone metastases who received 1st-line chemotherapy without bisphosphonates were analyzed. The median age of patients was 63 years and 49 (43%) of the 114 patients were women. 88 patients had a PS 1 (77%). Of 114 patients, 82 (74%) had pain at the time of beginning 1st-line chemotherapy, and 37 (32%) required narcotic analgesics for pain relief. Thirty-six of the 114 patients (32%) experienced at least 1 SRE during each clinical course. In 12 (32%) of the 37 patients who required narcotic analgesics, first SRE occurred within 2 months from the beginning chemotherapy. Conversely, in 77 patients without analgesics, the incidence of first SRE within 2 months was 7% (P < 0.001). Median survival time in all patients was 8.8 months. The patients who required narcotic analgesics had shorter overall survival than those without analgesics (6.4 vs. 12.2 months, respectively, P < 0.001). Conclusions: Severe pain was associated with shorter survival and a greater risk of early occurrence of SRE in NSCLC patients with bone metastases receiving 1st-line chemotherapy. These findings suggest need of adding bisphosphonates to chemotherapy for pain relief and prevention of SREs in the treatment of NSCLC patients with bone metastases. No significant financial relationships to disclose.
A prospective randomized controlled trial comparing 4-weekly versus 3-weekly adjuvant chemotherapy with gemcitabine after curative resection of biliary tract cancer.
Authors: Shin Nakahira, Shogo Kobayashi, Atsushi Miyamoto, Junzo Shimizu, Masaki Kashiwazaki, Shigeyuki Ueshima, Yong-Kook, Kim, Toru Kitagawa, Keizo Dono, Masaki Mori, Yuichiro Doki, Hiroaki Nagano
Journal: Journal of Clinical Oncology (2012)

345 Background: Resection of biliary tract cancer, employing pancreatoduodenectomy and major hepatectomy, is highly aggressive. Thus, postoperative gemcitabine cannot be administered employing a routine dosage protocol. We theorized that a 3-weekly protocol (days 1 and 8, every 3 weeks) of gemcitabine as adjuvant chemotherapy would be superior to the usually administered 4-weekly protocol (days 1, 8, and 15 every 4 weeks). Methods: The outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol were compared in a prospective randomized clinical setting. The primary endpoint was the treatment completion rate, while secondary endpoints were adverse events and recurrence-free survival. Results: We enrolled a total of 27 patients. Only two patients (14%) on the 4-weekly protocol and three (23%) on the 3-weekly protocol (p=0.8099) completed treatment with no omissions and/or dose modifications. Most of the remaining patients (70%) experienced grade 3/4 neutropenia. Relative dose intensities were 72% and 78%, respectively, with the 4-weekly and 3-weekly protocols. Recurrence-free survival rates did not differ significantly between the two protocols. Conclusions: Contrary to our hypothesis, the 3-weekly protocol did not produce superior results in terms of completion, adverse events or recurrence-free survival rates as compared to the standard 4-week protocol.
The effect of reflexology on quality of life in Iranian patients with breast cancer.
Authors: Shadan Pedramrazi
Journal: Journal of Clinical Oncology (2016)

90 Background: Breast cancer is one the most prevalent cancers among Iranian women. One of the complementary therapies is reflexology. The extant paper has been provided with the objective of determining the effect of reflexology on quality of life of patients with breast cancer undergoing chemotherapy in the breast disease center. Methods: This study is a randomized clinical trial which has been applied to 60 patients suffering from breast cancer under chemotherapy in breast diseases center, in 2012. The patients were selected randomly in three test, control and placebo groups. In test group, reflexology was implemented for 3 weeks and each session lasted half an hour. In placebo group, only relaxation techniques were implemented for 3 weeks, each session lasted 20-30 minutes. Control group received the routine therapies of breast cancer center. Results: Data were collected by standard questionnaires of EORTIC QLQ-C30.V.3 and EORTIC QLQ-BR23.V.3. The questionnaires were filled before intervention and two weeks after applying study. There was no significant difference in demographic characteristics or quality of life score of three groups, before intervention. Total score of quality of life was higher in interventional group compared to placebo group before and two weeks after intervention (p &lt; 0.001) Results also indicated a significant difference in total score of quality of life between three test, placebo, and control groups after intervention (p &lt; 0.001). A considerable improvement was noticed in the different aspects of quality of life in the test group compared to two other placebo and control groups. Conclusions: Reduction of pain, anxiety, nausea, and other symptoms related to cancer in patients suffering from cancer are assumed as the important cases of nursing cares focus, and precise nursing may diminish these symptoms considerably. Using reflexology in patients suffering from breast cancer may improve the quality of life as an effective method, and can be recommended for use in patients with breast cancer if it is supervised by health system personnel.
Outcomes of second-targeted therapy for mRCC: A retrospective chart review of community practices in the United States.
Authors: Eric Jonasch, James E. Signorovitch, Peggy L. Lin, Zhimei Liu, Kenneth W. Culver, Sumanta Kumar Pal, Jeffrey A. Scott, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2013)

424 Background: Sequential use of targeted therapies has become standard practice for the treatment of metastatic renal cell carcinoma (mRCC). This study describes treatment outcomes of the 2 nd -targeted therapy among patients with mRCC treated in the community setting. Methods: A retrospective chart review and survey was conducted during May through June 2012 among community-based oncologists or hematologists. Charts were reviewed for adult mRCC patients initiated on 2 nd -targeted therapy on or after January 1, 2010. Abstracted data included patient demographics, disease characteristics, treatment duration, dose adjustment, progression, mortality, and imaging test patterns. Kaplan-Meier analysis was used to estimate treatment duration, overall survival (OS) and progression-free survival (PFS) during 2 nd -targeted therapy. Patients were censored at the most recent contact. Results: Charts were reviewed for 433 mRCC patients. Mean age was 63 years at initial mRCC diagnosis and 64% were male. The most commonly used 2nd targeted therapies were everolimus (36% of patients), temsirolimus (17%), pazopanib (15%), and sunitinib (14%). The median duration of 2 nd -targeted therapy was 10.5 months (95% CI: 8.8-11.5). The majority of patients (73%) had no dose adjustment on 2 nd -targeted therapy; the most common reason for adjustment was drug toxicity (70%). Among the 44% of patients who discontinued 2 nd -targeted therapy, disease progression was the most common reason for discontinuation. The proportion of patients who received imaging test within 3, 6, and 12 months after 2 nd -line treatment initiation was 57%, 92%, and 99%, respectively. Routine monitoring (83%) was the most common reason for imaging tests. Median durations of OS and PFS after initiation of the 2 nd -targeted therapy were 30.4 months (95% CI: 23.5-not reached) and 10.7 months (95% CI: 8.4-12.2), respectively. Conclusions: In this large, retrospective chart review study, median treatment duration of 2 nd -targeted therapy was 10.5 months, median OS was 30.4 months, and median PFS was 10.7 months. Median treatment duration in community practice was longer than in clinical trials for targeted therapies in mRCC.
Patients’ preferences for adjuvant chemotherapy (ACT) in early colon cancer (ECC): What makes it worthwhile?
Authors: P. L. Blinman, V. M. Duric, A. K. Nowak, P. Beale, S. J. Clarke, K. Briscoe, A. Boyce, D. Goldstein, M. Hudson, M. R. Stockler
Journal: Journal of Clinical Oncology (2008)

4050 Background: ACT improves disease-free and overall survival at the expense of toxicities and inconvenience. We sought the minimum survival gains patients judged necessary to make ACT worthwhile and factors associated with their judgments. A secondary aim was to compare a self-administered questionnaire (PACT-Q) with a validated, scripted interview (PACT-I). Methods: All 123 subjects completed the PACT-Q; a subset of 100 also completed the PACT-I. The order of administration (PACT-I or PACT-Q first) was randomized. Subjects rated how troubled they were by various aspects of health related quality of life (HRQL) during ACT (from 0 = none at all, 10 = worst I can imagine). Associations between preferences and characteristics of the patient, disease, treatment and HRQL during ACT were assessed with linear regression after normal score transformation. Concordance of the PACT-I and PACT-Q was assessed with the intraclass correlation coefficient (ICC) and t-tests. Results: The median age was 65y (range 19–86), 52% were female and 70% had positive nodes. ACT was 5-FU alone in 73%, 5-FU + oxaliplatin in 12%, and was completed 1–3 years earlier in 52%. Over 70% of patients judged an additional 3 months in survival time or 1% in survival rate sufficient to make ACT worthwhile. Tertiary education was the only factor associated with preferences (larger benefits needed to make ACT worthwhile, p=0.01). The most troublesome aspects of HRQL during ACT (mean) were: fatigue (5.2), nausea (3.8), altered sense of taste (3.7), thought of having treatment (3.6) and diarrhoea (3.5), but none of these were significantly associated with patients’ preferences. Concordance between the PACT-I and PACT-Q was high (ICCs from 0.71–0.82), but the PACT-I gave higher values than the PACT-Q for scenarios with a better prognosis (p=0.04, 0.02). Few thought that answering the questionnaire was hard (10%) or stressful (6%) and most were glad they took part (91%). About half rated the interview and questionnaire ‘about the same’ on ease of understanding (44%), clarity (47%), and stressfulness (60%). Conclusions: Most subjects judged small benefits sufficient to make ACT worthwhile. The PACT-Q is a valid and acceptable way of eliciting preferences for adjuvant chemotherapy. No significant financial relationships to disclose.
Chemoprevention and epigenetic multitargeted approach.
Authors: M. A. Nezami
Journal: Journal of Clinical Oncology (2016)

e297 Background: In 2012 there were 11,957,599 advanced cancer cases in the US reported by CDC and the incidence has been almost unchanged over the previous 8 years (482,000 cases in 2000 versus 456,000 cases in 2008). There has been an annual percentage change of only (-0.6) between years 1999 to 2008 in cancer incidence. It is described in recent literature that epigenetic alterations are at least if not more important than genetic defects for the development and progression of malignant diseases. Transcriptional therapy is a very promising form of cancer treatment that is being extensively evaluated. It is speculated that inhibitors of DNA methylation and histone deacetylases can reactivate expression of tumor suppressor genes. Hypermethylation and transcription silencing of suppressor genes has been shown in 33% of breast cancers, 60% of prostate CA and 92% of colon CA. The value of combination therapy both in chemoprevention, as well as treatment in patients with cancer is extremely important and can cause a significant shift in the current practice of oncology and cancer prevention, the results in clinical studies have been poor as the target histone hyperacetylation does not correlate with survival (possibly due to P 16/21 resistance and unselectiveness of the conventional therapies/targets). Methods: In vitro application of epigenetic modifiers, consisting of nontoxic natural substances tested in cell cultures showed preliminary results confirming apoptosis. Application of the relevant scientific merits described above, using combination of epigenetic modifiers, and natural compounds in a protocol called Multi targeted epigenetic therapy (MTET) in a set of advanced patients showed synergistic effect which was clinically relevant. Results: Clinical application of this method of treating cancer has caused promising preliminary results. We present the summary of outcomes in one hundred cases of advanced cancer (refractory solid tumors) with thirteen cases, described in detail. Conclusions: Our preliminary findings were encouraging and supports further research in a large randomized trial to evaluate the efficacy of such method, in refractory and advanced solid tumors.
Microenvironment and cytokines in pseudomyxoma peritonei.
Authors: Kush Raj Lohani, Shreya Jagadish Shetty, Sean J. Judge, Govindarajan Venkatesh, Peter Thomas, Brian W. Loggie
Journal: Journal of Clinical Oncology (2013)

433 Background: Pseudomyxoma Peritonei (PMP), a peritoneal mucinous neoplasm of appendix origin, is associated with inflammation and fibrosis which is central to the disease biology. Here, we examine possible biomarkers or regulators of PMP biology in peritoneal tumor microenvironment and in serum. Methods: Ascites, peritoneal washings and serum were collected from PMP patients. Cytokines and C-reactive protein (CRP) levels were determined using Milliplex immunoassays. Immunohistochemistry (IHC) was performed on formalin-fixed tissue sections. Statistical analysis was performed by the Mann Whitney U test and Bivariate analysis. Results: Serum CRP was significantly elevated in PMP patients (n=29) versus controls (n=4) (0.124 vs 0.004 mg/dl, p = 0.003). CRP levels were lower in ascites (0.028 vs 0.124 mg/dl, p = 0.014), but correlated with serum levels (R = 0.65, p &lt; 0.001). Cytokines typically elevated after infection or injury—TNF-α, IL-1α, IL-1β and γ INF—were not significantly elevated in PMP ascites; however, IL-6, IL-8, IP-10 and MCP-1 were consistently higher (p &lt; 0.001) in PMP with ascites (n=29) when compared to control peritoneal washings (n=9). Both serum and ascites from 10 patients were evaluated for these four cytokines. Ascites levels were significantly elevated compared to their respective serum for IL-6 (1107 vs 3.18 pg/ml, p &lt; 0.001), IL-8 (167 vs 1.59 pg/ml, p &lt; 0.001), IP-10 (5454 vs 504 pg/ml, p &lt; 0.001) and MCP-1 (2420 vs 234 pg/ml, p = 0.002) but the serum levels were not significantly elevated compared to controls (n=6) (p = 0.31, 0.2, 0.63, 0.37 respectively). IHC revealed staining for IL-6 and IL-8 in stromal cells and focal staining of tumor for IP-10 and MCP-1. Recombinant IL-6-treated LS174T cells (mucinous colon cancer cell line) showed increased proliferation (p&lt;0.009) which was inhibited by anti-IL-6 antibodies (p&lt;0.004). Conclusions: CRP, a liver-synthesized marker of systemic inflammation, is elevated in PMP, and may have clinical utility. The results support local synthesis for cytokines IL-6, IL-8, IP-10 and MCP-1 in the peritoneum. Interestingly, the pattern of cytokines appears to be distinct from those following injury or infection. Further studies may yield novel targets for future treatment.