tbuckley/cabot-search huggingface dataset:
Is RCC truly radioresistant? Local control rates of metastatic renal cell carcinoma (RCC) to the lung using stereotactic radiotherapy (SBRT).
Authors: Basel M Altoos, Arya Amini, Maria Teresa Bourlon, Christine M. Fisher, Edward Bedrick, Thomas W. Flaig, Elaine Tat Lam, Elizabeth Riley Kessler, Brian D. Kavanagh, Sana D Karam
Journal: Journal of Clinical Oncology (2015)

445 Background: The use of radiation therapy (RT) for renal cell carcinoma (RCC) is controversial because RCC has traditionally been considered to be “radioresistant”. Based on this concern, current studies have suggested the need for higher doses with conventional fractionation (CF) or the use of SBRT with RCC. The purpose of this study is to determine the efficacy of these modalities by comparing the radiographic and symptomatic local control (LC) rates in patients with metastatic RCC to the lung. Methods: We retrospectively analyzed the radiographic and symptomatic RT response in 27 consecutive RCC patients with 37 RCC lung lesions treated between 2005 to 2014. Twenty-six (70.2%) were treated with SBRT and eleven (29.8%) with CF. Only 9 patients (33.3%) had symptoms prior to RT. Median SBRT dose and fraction was 50 Gy (range 25-60) and 3 (range 1-6) versus CF 30 Gy (range 20-55) and 10 (range 5-22) respectively. Toxicity was evaluated by CTCAE 4.0. Results: Median follow up was 16 months (range 1-102). Rates of radiographic local control with SBRT and CF were 92.3% vs. 55.4% respectively (p=0.0016). Under univariate analysis, predictors for radiographic LR were gross tumor volume (GTV) &gt; 20 cc (p &lt; 0.0001), planned tumor volume (PTV) of &gt; 100 cc (p &lt; 0.0001), and biologic effective dose (BED) &lt; 70 Gy (p=0.0001). Subanalysis of CF demonstrated that a BED &lt; 54 Gy was also a strong predictor for LR (p=0.0012). Under multivariate analysis, PTV was a strong predictor for radiographic LR (odds ratio [OR] = 42.2, p=0.0492). For the 9 symptomatic patients, 3 of 4 (75%) patients in the CF arm and 4 of 5 (80%) in the SBRT arm experienced partial or complete symptomatic relief. The median time to relief of symptoms in the SBRT and CF arms were 0.5 and 2 months, respectively. All patients receiving CF had symptomatic LR compared to none in the SBRT arm (p=0.0124). One patient in the SBRT arm had grade 2 hiccups and one with grade 2 pneumonitis in the CF arm. There were no other grade 2 toxicities or higher. Conclusions: SBRT demonstrated an encouraging local control rate and was capable of safely providing symptomatic relief to patients. The traditional view of radioresistance in RCC may not apply in the era of SBRT.
Venous thrombosis associated with central venous catheter in cancer patients with surgical chest port (S) or venography- guided arm port insertion (R): A randomized controlled study.
Authors: P. Marcy, E. Chamorey, A. Figl, M. Frenay, F. Peyrade, R. Largillier, J. Machiavello, J. Ferrero, E. Francois, J. Thariat
Journal: Journal of Clinical Oncology (2010)

9158 Background: The aims of this prospective randomized study were two-fold: To estimate the incidence of overall venous thrombosis (VT) including catheter-related upper extremity venous thrombosis in a low-risk oncology population; To study risk factors for catheter-related VT Methods: Adult patients with solid tumor malignancy eligible for central venous catheter (CVC) were randomized between surgical chest port (S) and venography-guided arm port insertion (R). Follow-up included clinical assessment, chest radiograph control of the catheter tip, 3-month Doppler Ultrasound screening of catheter-related VT and CT angiography. Exclusion criteria included previous VT or pulmonary embolism, previous ipsilateral venous catheter or pacemaker, ipsilateral central venous compression/irradiation, poor WHO performance status and anticoagulation Results: 215 patients (median age 59 years; range: 25-82) were eligible in 3 years. 106 CVC patients were assigned to S arm and 109 to arm R to yield a total of 32,075 and 29,007 catheter-days, respectively. Thirty-eight patients (17.7%) developed VT: 25 (66%) were related to CVC (ipsilateral), 14/25 (56%) were asymptomatic. Median interval between CVC implantation and thrombosis was 48 days (rge; 5-350). All had their catheter tip correctly positioned. The following items were significant risk factors for overall VT: tumor location (breast vs others- HR=3), UICC stage (O-2 vs 3-4 – HR=2.3). There was a trend for male gender and body mass index (BMI>23). Catheter-related VT rate was 0.044% per patient-day in 14/106 (S) patients vs 0.038% in 11/109 (R) (p= .48). Pulmonary embolism occurred in three patients. One (R) patient with VT died of anticoagulant therapy-related complication and one (S) patient developed persistent upper extremity edema. Conclusions: VT occurred in 17.7% of these cancer patients at low-risk of DVT including 66% related to ipsilateral CVC and 56% asymptomatic cases. Tumor location, UICC stage were significant risk factors for VT. Both surgical chest port (S) or venography-guided arm port were safe. There was no influence of either procedure on the rate of VT. No significant financial relationships to disclose.
Disease-related knowledge and attitudes among familial adenomatous polyposis kindreds.
Authors: Aimee S. James, Phillip Chisholm, Melanie Baxter, Nicholas Davidson
Journal: Journal of Clinical Oncology (2012)

423 Background: Familial Adenomatous Polyposis (FAP) is a highly penetrant autosomal dominant disorder, for which patients and their first degree relatives (FDRs) should receive genetic counseling in addition to regular endoscopic and clinical screening. Previous studies indicate under-use of screening and preventive care among FAP families but the reasons are not well understood. Our objective was to identify potential areas of need for information and support among FAP kindreds from a single center registry. Methods: FAP patients and FDRs were solicited to participate in a survey on health and information needs. Multiple attempts were made to reach potential respondents. Sixty-one patients were solicited and 40 surveys were collected (Response Rate = 61%). Survey respondents also recruited 10 additional FDRs. Participants (N=50) could choose to complete their survey online, by telephone, or on paper. Descriptive analyses were conducted using SPSS. Results: The average age of respondents was 50.2 years, 62% (n=31) were female; and 70% (n=35) had FAP. Among the responses to knowledge questions, half of respondents (n=25) stated that children who do not inherit FAP from their parents can still pass on the disease to their own children. In addition, only 62% (n=31) answered correctly that children of an affected FAP parent have a 50% risk of the disease ; nearly a quarter (n=12; 24%) said they did not know. Respondents also reported FAP-specific needs, including worries and concerns about children developing FAP (19% rated this as moderate or high), fears about developing cancer (33%), uncertainty about the impact of FAP (38%), dealing with the impact of FAP on the family (34%), obtaining medical information about FAP (37%), and understanding information relevant to FAP (31%). Conclusions: The data in this single center survey suggest that substantial knowledge gaps exist within FAP kindreds, both in affecteds and also FDRs. In particular, there was incomplete understanding regarding the heritable risks and also disease specific risks for children. These data indicate that members of FAP kindreds have unmet needs regarding their disease and risk, and want information that can help them manage their disease.
Oncoretroviral and Lentiviral Transduction of Donor T Cells to Facilitate Engraftment of Dog Leukocyte Antigen (DLA)-Haploidentical T-Cell-Depleted Marrow.
Authors: Dario Sangiolo, Marina Lesnikova, Alla Nikitine, Hans-Peter Kiem, Rainer Storb, Richard A. Nash, George E. Georges
Journal: Blood (2004)
Relationship between <i>ERCC1</i> polymorphisms, disease progression, and survivalin GOG0182, a Gynecologic Oncology Group phase III trial of platinum-based chemotherapy in women with advanced stage epithelial ovarian or primary peritoneal cancer
Authors: T. C. Krivak, K. M. Darcy, C. Tian, M. A. Bookman, B. A. Baysal, H. H. Gallion, C. B. Ambrosone, J. A. DeLoia
Journal: Journal of Clinical Oncology (2008)

5540 Background: We hypothesized that polymorphisms in excision repair cross-complementation group 1 (ERCC1), involved in nucleotide excision repair (NER) of platinum-induced damage, would be associated with progression-free survival (PFS) and overall survival (OS) in women with previously-untreated, advanced stage epithelial ovarian cancer (EOC) or primary peritoneal cancer (PCC) treated with platinum-based combination chemotherapy based on findings indicating that polymorphisms in codon 118 and C8092A are associated with improved OS in some cancers. Methods: Single nucleotide polymorphism (SNP) analysis was carried out by direct pyrosequencing at two sites (codon 118 and C8092A) in ERCC1 in leukocyte DNA from 280 women who were enrolled between 1/29/01 and 1/28/03 in the five-arm phase III trial (GOG-182) and had high quality DNA. Kaplan-Meier method with the logrank test was used to compare survival across genotypes. Cox regression modeling was performed with adjustments for prognostic covariates and treatment. Results: Polymorphisms in codon 118 or C8092A of ERCC1 were evaluated in 278 or 280 of the women in this study, respectively. The genotype distribution at codon 118 was 23% with C/C, 45% with C/T and 32% with T/T, and at C8092A was 50% with C/C, 42% with C/A and 8% with A/A. Median OS was 32, 47 and 43 months for the codon 118 C/C, C/T or T/T genotype in ERCC1, respectively. Adjusted Cox regression analysis revealed that the hazard ratio for death was 0.704 (95% confidence interval [CI]=0.494–1.003, p=0.052) for the codon 118 C/T genotype or 0.652 (95% CI=0.441–0.965, p=0.0325) for the T/T genotype compared with the C/C genotype. Median OS was 45, 40 or 30 months for the C8092A C/C, C/A or A/A genotype in ERCC1, respectively. Adjusted hazard ratio for death was 1.709 (95% CI=1.002–2.914, p=0.049) for A/A and 1.232 (95% CI=0.914–1.661, p=0.171) for C/A compared with the C/C genotype. Conclusions: When compared with the C/C genotype, the C/T and T/T genotypes in codon 118 of ERCC1 were associated with better survival, whereas the A/A genotype in C8092A of ERCC1 were associated with worse survival. These findings require validation. No significant financial relationships to disclose.
Duration of targeted therapy in metastatic renal cell carcinoma patients with ECOG PS>2.
Authors: Ilya Tsimafeyeu, Natalia N. Petenko, Anton Snegovoy, Sergey Varlamov, Lev V. Demidov
Journal: Journal of Clinical Oncology (2014)

520 Background: Targeted therapy has improved clinical outcomes in metastatic renal cell carcinoma (mRCC). However, patients with unfavorable performance status are often under-represented in clinical trials of mRCC. Methods: Patients with mRCC (clear or non-clear cell) and ECOG PS &gt;2 were included in retrospective study.Primary objective of this study was to evaluate the overall duration of targeted therapy (ODT). ODT was defined as time from initiation of first-line therapy until the end of last-line therapy. Results: 79 patients with ECOG PS &gt;2 (median age, 60 [48-70]; male, 73%; clear-cell RCC, 95%; MSKCC intermediate/poor risk, 97%/3%) were treated with sunitinib (77%), sorafenib (23%), everolimus (20%), bevacizumab + IFN (15%), pazopanib (4%), temsirolimus (2.5%) of which 55 (70%) received only first-line therapy, 24 (30%) received 2 lines, and 9 (11%) received 3 lines of therapy. The median ODT was 9.8 months (95% CI 6–13.6). The median time to progression of patients that received 1, 2 or 3 lines was 7.1, 5.9, and 6.3 months, respectively. One patient showed complete response and 2 patients had partial responses during first-line therapy, 2 patients had partial responses during second-line therapy, and 1 patient had partial response after 2 months of third-line therapy. Among the patients who discontinued treatment, disease progression was the most common reason for discontinuation. There was no unexpected serious toxicity. Conclusions: mRCC patients with unfavorable performance status could be treated with targeted therapy during 9.8 months.
Inguinal lymph node dissection for penile carcinoma: Postoperative complications using a validated classification system.
Authors: Isuru Sampath Jayaratna, Anirban Pradip Mitra, Raj Dedhia, Steven Asbaghi, Kara K. Teruya, Eric Tygenhof, Anne K. Schuckman
Journal: Journal of Clinical Oncology (2013)

326 Background: Inguinal lymph node dissection (ILND) is the gold standard for evaluating for locoregional disease in penile squamous cell carcinoma (PSCC), however, it has been previously described to have a high morbidity rate. We describe our postoperative complications using a validated classification system and examine possible associations with clinicopathologic factors. Methods: We retrospectively identified patients with a diagnosis of PSCC that underwent ILND at our institution from 1995 to 2012. Postoperative complications were characterized by the highest grade complication achieved by patients using the Clavien-Dindo classification system during the first 90 days after their surgery. Clavien-Dindo scores of 2 or less were defined as low grade, and scores of 3 or greater were defined as high grade. Univariate Cox regression analysis was performed to examine associations between complications and clinicopathologic factors. Results: We identified 36 patients who underwent ILND during this period, with 29 that had complete clinical, pathological and complication data. For the 50 ILNDs performed in our cohort, we report a 46% total complication rate, with a 36% low grade and a 10% high grade complication rate. Of the low grade complications, 39% were wound dehiscences that required wound packing, and 28% were wound infections that required antibiotic treatment. The highest grade of complications achieved was 3A, all of which were lymphoceles that required percutaneous drainage for resolution. We were unable to demonstrate any association of complications with age, ethnicity, tumor stage, tumor grade, AJCC stage, presence of palpable lymphadenopathy or pathologic nodal stage. Conclusions: While ILND still remains an operation with high morbidity, our findings show that the most common low grade complications can be managed with medications and dressing changes, and the relatively modest high grade complication rate consists entirely of percutaneous drain placement. The inability to show associations with clinicopathologic variables is likely due to our low sample size. These findings support the continued use of ILND for staging in PSCC.
Detection of IDH1 mutations in a series of 91 oligodendrogliomas: Comparison of immunohistochemistry, DNA sequencing, and allele-specific PCR.
Authors: D. Loussouarn, A. Le Loupp, J. Frenel, F. Leclair, A. Von Deimling, M. Aumont, S. Martin, M. Campone, M. G. Denis
Journal: Journal of Clinical Oncology (2011)

2020 Background: IDH1 mutations have been indentified in about 70% of WHO grade 2 and 3 astrocytomas and oligodendrogliomas, conferring a better prognosis. The most frequent mutation leads to a specific amino-acid change from arginine to histidine at codon 132 (c.395G>A, p.R132H). We compared mIDH1 R132H immunohistochemistry, allele specific PCR and DNA sequencing for determination of IDH1 status. Methods: We performed a retrospective study of 91 WHO grade 2 (n=43; mean 40.6 years) and grade 3 (n=48; mean 50 years) oligodendrogliomas, diagnosed in the Neurosurgery Department of Nantes. Immunohistochemistry was performed with mouse monoclonal mIDH1 R132H (gift von Dr von Deimling, Heidelberg, Germany). DNA was extracted from FFPE sections following macrodissection using an iPrep system. A fragment of exon 4 (122 bp) spanning the sequence encoding the catalytic domain of IDH1 including codon 132 was amplified and sequenced using standard conditions. Allele specific amplification was performed using forward primers with variations in their 3′ nucleotides such that each was specific for the wild type or the mutated variant. Results: DNA could be amplified in 90 cases. IDH1 mutations were found in 55/90 patients (61.1%) by direct sequencing. Among these patients, R132H mutations was found in 47/55 patients (85.4%). The results of the allele specific PCR was totally correlated to DNA sequencing. Other mutations (p.R132C, p.R132S and pR132G) were found by DNA sequencing in 3, 3 and 2 tumors, respectively (8/55 patients, 14.6%). mIDH1 R132H immunostaining was found in the 47 patients presenting the R132H mutation (sensitivity 47/47 = 100% for this mutation). None of the tumors presenting a wild type IDH1 gene were stained (specificity 35/35 = 100%). Conclusions: Immunohistochemistry with mIDH1 R132H antibody is feasible, even in case of small biopsies, highly sensitive and specific. Because it only recognizes the most frequent mutation of IDH1 gene, immunohistochemical negative cases must then be tested by allele-specific PCR or DNA sequencing.
Prevention and palliation of hand-foot skin reaction (HSFR) due to the multikinase inhibitors (MKIs): An evidence-based assessment of the published peer-reviewed literature
Authors: M. E. Lacouture, R. T. Anderson, A. Jatoi, L. Wood, S. Fourt, K. N. Keating
Journal: Journal of Clinical Oncology (2008)

20588 Background: Significant advances in cancer outcomes with MKIs have resulted in cutaneous side effects such as HFSR. While HFSR symptoms are usually mild, affecting up to 30% of pts treated newer oral agents, HFSR may impair QoL and limit cancer treatment duration or intensity. Understanding the existing evidence for prevention and palliation of HFSR to generate appropriate clinical trial design and develop evidence-based prevention and palliation guidelines is important. Methods: Sixteen separate searches of the NLM PubMed database were conducted using search terms and combination of terms relevant to anticancer therapies and HFSR. Supplemental searches were performed on the Cochrane Reviews, BIOSIS, CancerLit and ASCO website. Articles were categorized as 1: (MKI + HFSR), 2: (MKI + other skin toxicity), 3: (other antineoplastic agents + HFSR) and 4: (other). The primary focus was on Category 1 articles reporting on HFSR treatment efficacy and patient outcome. Two reviewers independently reviewed and coded all titles and/or abstracts. Results: The searches yielded 2057 articles of which 338 (16%) met inclusion criteria for codes 1–4. 44 (13%) of these were Category 1 pertaining to MKIs with details of HFSR histology, pathogenesis, clinical outcome, QoL impact, and/or prevention and treatment approaches; 270 (80%) were Category 3 pertaining to other antineoplastic agents with details of those above. No Category 1 or 3 articles on prevention/palliation approaches to HFSR were randomized controlled trials. Approaches were classified as anecdotal or case reports, and included measures such as dose reductions, pedicures and sandals during anticancer therapy. Systemic/local strategies were presented, including pyridoxine, urea-based creams and corticosteroids. 1 article presented a meta analysis of 4 phase I sorafenib dose-escalation trials and showed a preliminary correlation of ≥ grade 2 skin toxicity/diarrhea with a significantly longer TTP. Conclusions: The literature does not include empirical evidence for optimal prevention or palliation of HFSR to MKIs. Evidence-based palliative approaches to skin toxicities from MKIs are clearly needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer Bayer
Quantifying alkylating agent exposure: Evaluation of the cyclophosphamide equivalent dose—A report from the Childhood Cancer Survivor Study.
Authors: D. M. Green, V. G. Nolan, D. K. Srivastava, W. Leisenring, J. P. Neglia, C. A. Sklar, M. M. Hudson, L. Diller, M. Stovall, L. L. Robison
Journal: Journal of Clinical Oncology (2011)

9547 Background: The Alkylating Agent Dose (AAD) score has been widely employed previously for quantifying alkylating agent exposure in analyses of second malignant neoplasms, mortality and fertility of adult survivors of childhood cancer. However, the AAD is calculated based on the the drug dose distribution of each study in which it is utilized, making comparisons across studies difficult and limiting its usefulness for counseling. Methods: We normalized alkylating agent doses to a cyclophosphamide equivalent dose (CED) using published toxicity and/or treatment data and evaluated the CED in an analysis of risk of pregnancy of partners of 4,797 male participants in the Childhood Cancer Survivor Study who were 15 to 44 years of age when they completed the baseline questionnaire. Cox proportional hazard models with age as the time-scale were used to compare hazards of a pregnancy between same age subjects. Univariable and multivariable analyses were carried out, with final treatment variables included in the multivariable model that were significant at the 0.1 level or that markedly influenced (>10% change) the effect of another factor in the model (confounder). Demographic, socioeconomic and exposure variables were evaluated for inclusion in multivariable models. Results: The hazard radio (HR) for siring a pregnancy, adjusted for demographic and other treatment variables, decreased with increasing CED (Table). Comparison of results using the AAD versus the CED, demonstrated better model fit with CED. Conclusions: Increasing CED is correlated with decreasing HR for siring a pregnancy. CED was a better predictor of pregnancy than the AAD. Since CED is independent of the drug dose distribution of the cohort being evaluated and can be compared across studies this approach should be incorporated into analyses assessing long-term outcomes associated with alkylating agent exposure. CED (mg/m2) HR 95% confidence interval P value 0 1.00 > 0 to < 4,000 0.97 0.66, 1.43 0.8729 ≥ 4,000 to < 8,000 0.73 0.51, 1.05 0.0873 ≥ 8,000 to < 12,000 0.48 0.33, 0.70 0.0001 ≥ 12,000 to < 16,000 0.36 0.22, 0.59 <0.0001 ≥ 16,000 to < 20,000 0.49 0.29, 0.84 0.0089 ≥ 20,000 0.21 0.12, 0.38 <0.0001