tbuckley/cabot-search huggingface dataset:
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a setting of chemotherapy treatment: An assessment of FDA MedWatch database.
Authors: V. Garg, Y. Balagula, D. W. Raisch, M. J. Anadkat, M. E. Lacouture
Journal: Journal of Clinical Oncology (2011)

e19519 Background: The association of chemotherapy with potentially fatal adverse events such as SJS/TEN has not been systematically examined. Case reports in association with agents such as imatinib and docetaxel have been published in the literature. We applied data mining algorithms to assess the risk of SJS/TEN to chemotherapy. Methods: FDA Safety Information and Adverse Event Reporting Program MedWatch database was searched for cases of SJS and TEN reported in association with FDA-approved chemotherapy agents through December 2009. Proportional reporting ratios (PRR>2) and empirical Bayes geometric mean (EBGM>2) with a case count threshold ≥3 were considered signals of disproportionate reporting. Cases obtained by searching this database included those in which chemotherapeutic agents were used to treat cancer and non-cancer-related diseases. Results: Using our criteria for selection of cases, we have identified 252 TEN cases associated with 11 FDA-approved drugs. Similarly, 71 SJS cases in association with 4 FDA-approved chemotherapy agents were identified (Table). Conclusions: By identifying disproportionally reported agents we demonstrated that multiple chemotherapy agents may be associated with SJS/TEN. Although data mining may not be sufficient to establish causality, this method may serve as a supplemental tool to identify chemotherapy drugs that may warrant further investigation. Drugs Cases Signal n PRR 95% CI EBGM 95% CI SJS Bendamustine 8 6.67 3.34-13.28 5.54 2.33-10.85 Chlorambucil 10 2.66 1.43-4.93 2.21 1.16-3.92 Ibritumomab tiuxetan 17 4.64 2.48-7.65 3.52 1.88-6.03 Temozolomide 36 2.16 1.56-2.99 2.07 1.47-2.82 Total 71 TEN Bendamustine 5 9.53 3.97-23.32 7.21 2.39-16.38 Busulfan 17 3.85 2.39-6.18 3.29 2.00-5.245 Cytarabine 55 2.67 2.05-3.48 2.56 1.94-3.30 Chlorambucil 12 6.19 3.52-10.88 5.67 3.04-9.69 Dactinomycin 8 3.81 1.90-7.60 2.82 1.36-5.57 Fludarabine 40 3.62 2.65-4.93 3.37 2.44-4.56 Ibritumomab tiuxetan 4 2.96 1.11-7.86 1.93 0.69-4.52 Lomustine 14 17.17 10.23-28.79 14.81 7.49-24.27 Procarbazine 24 5.51 3.69-8.2 5.18 3.3-7.62 Thiotepa 8 4.84 2.42-9.66 3.38 1.59-6.81 Vincristine 65 2.12 1.65-2.7 2.06 1.6-2.6 Total 252
The surfactant protein B (SFTPB) as a surrogate of circulating tumor cells (CTC) with prognostic value in advanced-stage NSCLC.
Authors: R. Sirera, E. Jantus-Lewintre, A. Timon, M. Usó, A. Berrocal, S. Borrego, G. Marcaida, E. Sanmartin, R. Rosell, C. Camps
Journal: Journal of Clinical Oncology (2011)

7596 Background: The detection of CTCs in the peripheral blood of cancer patients is of great interest in oncology but remains technically challenging. Molecular methodologies such as QRT-PCR are highly sensitive, specific and reproducible, but the use of appropriate mRNA markers for CTCs is required. The aim of the present study, in a cohort of advanced NSCLC, was to analyze eight CTC’s associated markers using QRT-PCR pre- and post-chemotherapy, and to correlate them with clinico-pathological variables and prognosis. Methods: RNA was obtained from peripheral blood samples preserved in PAXgene tubes (whole blood) of 69 NSCLC patients and 59 healthy age-, gender-matched controls. Patient’s samples were obtained before and after 3 cycles of chemotherapy with cisplatin and docetaxel. Eight genes surrogate of CTCs were selected in silico (CEA, CK19, CK20, CK7, SFTPB, AGR2, S100A13 and hTERT), mRNA was reverse transcribed and QRT-PCR was performed using TaqMan technology, GUS-B as endogenous control and a cell line as a calibrator. Differences were considered significant at p ≤0.05. Results: Median age 59.2 [37.1-75.5]; 84.1% males; 73.9 % stage IV; 30.4% squamous cell, 50.7% adenocarcinomas and 18.8% other histologies. We found significant differences in the expression of SFTPB between controls and patients (14.6 vs 25.6 respectively, p=0.05). Splitting the patients into two groups according to median gene expression levels, it could be observed that overall survival was significantly higher in patients with lower levels of SFTPB, 14.6 vs 10.8 months (p= 0.049). Conclusions: Quantification of CTC’s associated markers by QRT-PCR is technically possible in whole blood. SFTPB levels are significantly higher in NSCLC patients than controls. Patients with higher levels of this gene presented poorer overall survival. Validation with an independent group of patients is necessary in order to assess their role as diagnostic and/or prognostic biomarker. Supported by RD06/0020/1024 grant by ISCIII.
Expression of embryonic stem cell factor Sox2 in serous ovarian carcinomas.
Authors: T. N. Fehm, D. Pham, V. Scheible, C. Lengerke, S. Perner, H. Neubauer, A. Staebler
Journal: Journal of Clinical Oncology (2011)

5039 Background: The transcription factor Sox2 is involved in the maintenance of embryonic stem cell pluripotency and is expressed in several carcinoma types such as adenocacinoma of the lung and squamous cell carcinomas (SCC) of various origins. The gene SOX2is located at chromosome 3q26, a region that is a frequently amplified in serous ovarian carcinoma. Therefore, the aim of this study was to explore the potential role of Sox2 in ovarian carcinogenesis by correlating Sox2 protein expression in 167 serous ovarian carcinomas with clinical outcome. Methods: 167 consecutive cases of serous ovarian carcinoma were analyzed by immunohistochemistry and in a tissue microarray for nuclear expression of Sox2. The cut-off level for Sox2 positity was > 0% stained cells (Lengerke et al. BMC 2010). Correlation with clinicopathological factors were determined by chi-squared test. Recurrence-free and overall survival was compared by the logrank-test. Results: 57% of all 167 serous ovarian carcinomas showed detectable Sox2 positive cells. Sox2 expression was associated with grade 3 tumors (p<0.05). No correlation could be observed with FIGO stage (p=0.15) or nodal status (p=0.81). Sox2 had a significant impact on survival in patients with serous ovarian cancer (excluding G1 and FIGO I tumors). The median recurrence-free survival was 29.2 months (95%CI: 19.9 - 38.5 months) in the Sox2 negative group compared to 43.2 months (95%CI: 33.6 - 52.8 months) in the Sox2 positive group (p< 0.05).The overall survival was also shorter in the Sox2 negative group (40.3 months (95%CI: 29.1 - 51.5 months) versus 52.5 months (95%CI: 43.6 - 61.3 months) but did not reach statistical significance (p=0.06). Conclusions: Sox2-positive cells can be detected by immunohistochemistry in a majority of serous ovarian carcinomas. Interestingly, Sox2 expression is associated with a significantly better prognosis, suggesting that in this specific tumor entity activation of certain stemness-pathways may unexpectedly predict favourable outcome which may be related to increased platin sensitivity.
Prognostic factors for lung cancer patients with brain metastases treated with whole brain radiotherapy
Authors: N. Horiuchi, H. Okamoto, N. Hida, K. Naoki, T. Shimizu, K. Watanabe, A. Ishizaka
Journal: Journal of Clinical Oncology (2008)

7570 Background: The purpose of this retrospective study was to clarify the role of whole brain radiotherapy (WBRT) in lung cancer patients with brain metastases (BM). Methods: Between February 1998 and October 2005, 103 consecutive lung cancer patients received WBRT for BM. The patients included 77 men and 26 women, ranging in age from 34 to 84 years with a median age of 65 years. Thirty-six of the patients had SCLC and 67 had NSCLC. Fifty-two patients had an ECOG performance status (PS) score of 0 to 2, and 51 had a PS score of 3 or 4. Seventy-nine patients (77%) had symptomatic BM, and 72 had multiple BM (70%). The mean dose of brain radiation was 38±8.3 Gy. Following radiation treatment, the median survival time (MST) for all patients was 4.0 months, and the 1-year survival rate was 14%. Multivariate analysis was performed using Cox proportional hazards model to evaluate the following: sex, age (<60 years vs. ≥60 years), histology (SCLC vs. NSCLC), PS score (0–2 vs. 3–4), number of BM (single vs. multiple), the presence or absence of neurological symptoms, the presence or absence of other metastases outside the brain, and lastly, any extracranial disease activity, including active or inactive primary lesions. Results: WBRT improved the neurological symptoms in 45 patients out of 75 symptomatic patients (60%). When multivariate analysis was performed, the favorable prognostic factors consisted of females (p=0.017), a PS score 0–2 (p=0.006), and extracranial disease activity including primary lesions (p=0.004). Based on these three prognostic factors, we subdivided the patients into four groups; the low-risk group had no risk factors, the mild-risk group had one, the moderate-risk group had two, and the high-risk group had three. The MST for the four subgroups was as follows: 548 days for the low-risk group, 195 days for the mild-risk group, 95 days for the moderate-risk group, and 58 days for the high-risk group. Conclusions: Although WBRT was an effective palliative treatment for lung cancer patients with BM, the MST for the high-risk group was somewhat disappointing. Further studies are necessary to evaluate quality of life and MST with or without WBRT for high-risk group patients with lung cancer. No significant financial relationships to disclose.
Standardizing coordination between surgical oncology and reconstructive surgery for breast cancer patients undergoing mastectomy with immediate reconstruction.
Authors: Mehra Golshan, Charles A. Hergrueter, Kristen Camuso, Nancy U. Lin, Linda Cutone, Judith Hirshfield-Bartek, Phil Roberts, William Runkle, Sarah Kadish, Katya Losk, Craig A. Bunnell
Journal: Journal of Clinical Oncology (2014)

110 Background: Timely diagnosis and treatment of breast cancer, endorsed by organizations such as ASCO and NCCN, are essential to ensure optimal clinical outcomes and patient satisfaction. Inefficient care coordination may adversely affect care quality. At our cancer center, 75% of patients who undergo mastectomy seek a reconstructive surgery consult and over 60% elect mastectomy with immediate reconstruction. We sought to evaluate and reduce the time to reconstructive surgery consult and first definitive surgery (FDS) by streamlining coordination between services. Methods: We studied 330 patients who underwent mastectomy with immediate reconstruction between January 2011 and April 2013. Time intervals between initial surgical consult, reconstruction consult, and FDS were calculated. After examining existing best practices in patient referral and scheduling, we established targets of 7 days from initial consult to reconstruction consult and 28 days from initial consult to FDS. To achieve these targets, facilitated sessions were held with administrative and clinical experts to create a standard referral and scheduling process, including a referral template and establishing surgical teams based on clinic and operating room alignment. The interventions were implemented over a 6-month period. Results: Mean days from initial consult to reconstructive surgery consult decreased, with significant improvement in reaching the 7 day target. No significant changes from time of initial consult to FDS were observed. Conclusions: Standardizing coordination has led to timelier reconstructive surgery consults for patients undergoing mastectomy with immediate reconstruction. Other factors, such as operating room availability, pre-operative testing and patient preference should be explored to reduce the time to FDS. [Table: see text]
Targeted anti-inflammatory and angiostatic therapy in pretreated patients with advanced hepatocellular carcinoma
Authors: A. Reichle, S. Walpinski, M. Vogelhuber, K. Wiedmann, A. Berand, E. Endlicher, F. Klebl, J. Schölmerich, R. Andreesen, R. Wiest
Journal: Journal of Clinical Oncology (2008)

15560 Background: Targeting tumor systems biology in patients with advanced and pre-treated hepatocellular carcinoma (HCC) with a combined anti-inflammatory and angiostatic treatment strategy. Methods: In a prospective one arm, one stage multi-center phase II trial (recruitment from February 2004 to November 2006) patients with measurable, histologically proven, inoperable, progressive HCC, either treatment-naïve or with local and/or systemic pre-treatment, and Child-Pugh A, received continuous oral pioglitazone 60mg daily, day 1+, etoricoxib 60 mg daily, day 1+, as anti-inflammatory treatment and 1g absolute capecitabine bid for 14 days, every 3 weeks as angiostatic therapy (starting day 1+) until tumor progression. Tumor response was assessed every 6 weeks using modified WHO criteria. Primary endpoint was time to progression (TTP), estimated sample size 35 pts. Results: Of 38 patients (pts) treated (male 74%, median age 61 years) CLIP score was 0 (5%), 1 (56%), >1 (39%), 26 pts (68%) were locally (TACE or surgery), 11 (29%) systemically pretreated, 14 pts (26%) received first-line, and 24 pts (74%) second to forth-line therapy. On the basis of independent response assessment 11 (29%) had stable disease for at least 4 months. Disease stabilization occurred in 5 of 13 (38%) locally pre-treated pts, in 4 of 11 pts (36%) systemically (and locally) pretreated, and in 2 of 14 treatment-naïve pts (14%). All pts were eligible for the primary endpoint. Median TTP was 3.4 months (CI 95%, 2.29 to 4.51 months) and median overall survival 6.7 months (CI 95%, 4.08 to 9.32 months). Grade 3/4 drug-related toxicities included edema 13%, hand-foot-syndrome (8%), and anaemia (3%). Conclusions: Although modest efficacy was observed, the biomodulatory treatment schedule may rescue patients locally and/or systemically pretreated by disease stabilization at a low rate of treatment-associated toxicity. No significant financial relationships to disclose.
Association of sunitinib pharmacokinetics with toxicity and genetic polymorphism in efflux transporter ABCG2 in patients with renal cell carcinoma.
Authors: T. Mizuno, M. Fukudo, T. Terada, T. Kamba, E. Nakamura, O. Ogawa, K. Inui, T. Katsura
Journal: Journal of Clinical Oncology (2011)

e15030
Prognostic and predictive significance of insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), and HER2 in metastatic colorectal cancer
Authors: Y. Yamada, A. Goto, T. Ura, H. Yasui, K. Kato, T. Hamaguchi, K. Muro, Y. Shimada, T. Shimoda, K. Shirao
Journal: Journal of Clinical Oncology (2005)

9649 Background: The IGF1-R and HER families play critical roles in the regulation of cellular proliferation and transformation. IGF-1, EGF, and other ligands inhibit apoptosis and promote tumor growth. Therefore, the IGF system as well as EGFR and HER2 might be appropriate targets for therapeutic intervention. Methods: We retrospectively analyzed the prognostic and predictive clinical values of IGF-1R, EGFR, and HER2 by immunochemical techniques in colorectal cancer treated with fluorouracil (FU) followed by CPT-11. Results: EGFR, IGF-1R, and HER2 expression was evaluated in 72 consecutive patients with metastatic colorectal adenocarcinoma. Sixty-nine of the 72 (96%) cases expressed IGF-1R, and 53 (74%) were classified as positive (≥10% positive cells). Sixty-six of the 72 (92%) cases expressed EGFR, and 51 (71%) were classified as positive (same criteria as above). Only one case (1%) was positive for HER2. Progressive disease (PD) after second-line treatment with CPT-11 was observed in 15 of 40 (38%) IGF-1R positive patients and 1 of 12 (8%) IGF1-R negative patients (P=0.077). PD after first-line treatment with FU was seen in 3 of 19 (16%) IGF1-R positive patients and 12 of 53 negative patients (P=0.74). There was no correlation between EGFR expression and the response rate to 5-FU (P=0.35) or CPT-11 (P=0.74). Median survival times from the start of FU treatment were 18.9 months in EGFR-positive patients and 16.8 months in EGFR-negative patients (P=0.015). Median times to progression from CPT-11 treatment were 3.4 months in EGFR-positive patients and 3.1 months in EGFR-negative patients (P=0.11). There was no correlation between IGF1-R expression and overall survival time or time to progression. Conclusions: EGFR was a significant prognostic factor for patients with metastatic colorectal cancer treated with chemotherapeutic agents. IGF1-R could be a predictor of the response to CPT-11. No significant financial relationships to disclose.
Advance care planning and palliative care consultation for stem cell transplant patients.
Authors: Winnie S Wang, Joseph D. Ma, Sandahl H Nelson, Carolyn Revta, Gary T Buckholz, Carolyn M. Mulroney, Eric Roeland
Journal: Journal of Clinical Oncology (2016)

113 Background: Advance care planning (ACP) in stem cell transplantation (SCT) is particularly challenging given the potential for cure for patients with blood cancers despite an increased risk of suffering and even death. Data regarding ACP and palliative care (PC) integration in SCT is limited. Methods: A retrospective chart review was conducted of patients with hematologic malignancies who underwent SCT at UCSD from January 2011 to December 2015. The primary objective was to determine the medical discipline of the initial and last code status documentation. Secondary objectives included evaluation of AD and/or POLST completion, PC consultation, hospice enrollment, and location of death. Data were compiled from a single electronic medical record and descriptive statistical analyses performed. Results: A total of 633 SCT were performed from 2011 to 2015 including 39% (n = 245) allogeneic and 61% (n = 388) autologous transplants (n = 29 patients had 2 transplants). Mean age of SCT patients was 55 years (±13). All but one (n = 632) had code status documentation, and 0.8% (n = 5) were initially DNR. The initial code status was documented outpatient for 3% (n = 17), and by the primary SCT physician for 1 patient. The final code status was documented outpatient for 22% (n = 14), and by the primary SCT physician for 0.9% (n = 6). Nearly half (44%, n = 279) had an AD and/or POLST completed. PC consultation occurred for 19% (n = 121) with the majority (83%, n = 101) completed inpatient. PC consultation requests were made by the primary SCT physician (18%, n = 22), inpatient SCT team (68%, n = 82), critical care (8%, n = 10), or other (5%, n = 6).The most common reason for consultation was symptom management (80%, n = 94). As of January 2016, 20% (n = 127) of SCT patients died with a mean time from transplant of 312 days (± 317). Of those that died, the majority (83%, n = 106) died in the hospital, 15% (n = 19) were full code, 48% (n = 62) had an AD and/or POLST, and 14% (n = 18) were enrolled in hospice. Conclusions: These single center data suggest ACP and PC integration in SCT is limited. Opportunities exist to expand integration to the outpatient setting and earlier in the course of illness.
Does hospital academic status impact colon cancer care value?
Authors: Christine Marie Veenstra, Andrew J Epstein, Craig Evan Pollack, Katrina Armstrong
Journal: Journal of Clinical Oncology (2014)

6 Background: Given the high cost of cancer care, delivery of high-value care is crucial. The effect of hospital academic status on value of care for patients with stage II and III colon cancer is unknown. Methods: SEER-Medicare cohort study of 20,118 patients age 66+ with stage II or III colon cancer diagnosed 2000-2005 and followed through December 31, 2007. Patients were assigned to a treating hospital based on hospital affiliation of the primary oncologist. We constructed Kaplan-Meier curves to assess unadjusted overall survival. We estimated a Cox proportional hazards model to assess adjusted overall survival. To examine associations between hospital academic status and mean cost of care we estimated a generalized linear model (GLM) with log link and gamma family. We estimated quantile regression models to examine associations between hospital teaching status and cost at various quantiles (25th, 50th, 75th, 90th, 95th, 99th, 99.5th, 99.9th). Standard errors were adjusted to account for clustering of patients within hospitals. Results: 4449/20,118 (22%) patients received care from providers affiliated with academic hospitals. There was no significant difference in unadjusted median survival based on hospital academic status for patients with stage II (academic 6.4 yrs vs. non-academic 6.3 yrs, p=0.711) or stage III disease (academic 4.2 yrs vs. non-academic 4.2 yrs, p=0.81). After adjustment, treatment at academic hospitals was not associated with significantly reduced risk of death from colon cancer (stage II HR 1.05, 95% CI: 0.97 - 1.13; p=0.23; stage III HR 0.99, 95% CI: 0.94-1.07; p=0.98). Excepting stage III patients at the 99.9th percentile of costs, there were no significant differences in adjusted costs between academic and non-academic hospitals. Conclusions: We find no difference in overall survival for patients with stage II or stage III colon cancer based on academic status of the treating hospital. Furthermore, costs of care are similar between academic and non-academic hospitals across virtually the full range of the cost distribution. Most colon cancer patients do not receive cancer care at academic hospitals. Our findings indicate that for patients with stage II or III disease, this inequity does not impact the value of care.
Phase II trial of sorafenib and capecitabine for hepatocellular carcinoma in cirrhotic patients.
Authors: Yehuda Z. Patt, M Houman Fekrazad, Kim A Steinberg, Julie E. Bauman, Sang-Joon Lee, Fa-Chyi Lee
Journal: Journal of Clinical Oncology (2012)

341 Background: Sorafenib (sorf.) has become the standard treatment for Hepatocellular Carcinoma (HCC), demonstrating an increase in patients (pts) median survival from 7.9 to 10.7 months (m) (Llovett, NEJM 2008). Abou-Alfa added doxorubicin to sorf. observing a median survival of 13.7 m vs 6.7 m. for doxorubicin + placebo, (JAMA. 2010). Since most of our HCC pts were cirrhotic and 8/12 HCV +, and 2/12 HBV only +, with cirrhosis and thrombopenia we chose to add capecitabine (cap) to sorf in a phase II trial, anticipating better tolerance. Primary objectives were to assess safety and tolerability of the combination while secondary objectives included estimations of PFS, OST and documentation of disease control rate (DCR = CR+PR+SD). With relaxation of eligibility criteria C-P B-7 pts and ≥ 50,000 platelets were allowed. Methods: Sorf dose was 400 mg BID with dose adjustments for sorf related hand foot syndrome (HFS). Starting cap dose was 850mg/m2 BID x 7 Q 14 and adjusted as tolerated to 650mg/m2 BID or to 500 mg/m2 BID x 7 Q 14.. The lowest dose used was 250 mg/m2; BID (500 mg BID) for 5 days Q14. Patients: Only 12 of about 30 assessed patients met eligibility criteria, and were recruited between Nov. 2, 2009 and Sep. 13, 2011.The protocol was reviewed and approved by the WIRB and all participants signed an IRB approved consent form. Results: Preliminary Results: Eight of 12 patients are alive, survivals ranging from 2.5 to 23 m. One patient has an unmaintained radiological CR continuing for 23 months with an AFP decrease from 139 to 2.9. Another patient had a PR and an AFP decrease from 355 to 3.2 ng/mL. She died in PR at 13 months from an UGI bleed. Grade 3 and 4 toxicities were limited to the skin, and included HFS, in 4/12, skin ulcers at sites of prior osteomyelitis (1/12); requiring treatment cessation, and fatigue in 4 /12. Conclusions: With meticulous attention to cap dose adjustments as dictated by HFS this combination can be tolerated longitudinally in these frail pts that are not candidates for adding more aggressive agents to sorf. The objective radiological responses corroborated by AFP decreases in this very small cohort suggest that the findings are real, and warrant expansion of the trial.