tbuckley/cabot-search huggingface dataset:
Effect of contralateral prophylactic mastectomy on quality of life in women undergoing surgery for breast cancer: A prospective study.
Authors: Chang Xia, Mary C. Schroeder, Ronald Weigel, Sonia L Sugg, Alexandra Thomas
Journal: Journal of Clinical Oncology (2014)

9566 Background: There has been a marked increase in the use of contralateral prophylactic mastectomy (CPM) for women with unilateral breast cancer. Previous studies on quality of life (QoL) measures for women who have undergone CPM are mixed. Most surveys were conducted only post-operatively. This analysis reports QoL changes within the same patient before and after surgery, using a validated tool. Methods: This study includes women who were prospectively enrolled in the University of Iowa Breast Molecular Epidemiologic Resource. We included all women who had mastectomy on the affected side. Patients completed a validated QoL survey (FACT-B) which covered: overall QoL and additional cancer-specific concerns. Responses followed a five-point scale. Surveys must have been completed any time before surgery and 6-18 months after surgery. A Fixed Effects linear regression model was used to discern within-person changes in QoL measures before and after surgery. Analysis was stratified by unilateral mastectomy (UM) or CPM. Results: The study cohort included 34 women, 17 received CPM and 17 received UM. Mean age was 61.5 for women who chose UM and 50.6 for women who chose CPM (p <0.001). There were no differences in baseline QoL measures between the two groups. After surgery, both groups felt less nervous, though the change in the CPM group was greater (p<0.001). There were no other differences for the UM group in pre-post QoL measures. Women undergoing CPM did have QoL decrements (Table). Conclusions: Women who chose CPM feel less nervous after surgery. However, these women lose some sense of femininity and are more likely to experience physical post-operative sequelae. This adds to knowledge that can be used to counsel women about physical and emotional costs associated with CPM that manifest 6-18 months after surgery. QoL: Pre to postoperative change UM CPM Pre-post change p Pre-post Change p I feel nervous -1.18 <0.001 -1.46 <0.001 I am able to feel like a woman 0 1.0 -1.18 0.01 I have certain parts of my body where I experience pain 0.73 0.21 1.18 0.03 Movement of my arm is painful 0.57 0.14 0.88 0.03 I have stiffness of my arm 0.43 0.27 0.63 0.04 My arm feels numb 0.43 0.60 1.13 0.07
Should sentinel node biopsy (SNB) be restricted to breast cancer-dedicated surgeons? A single institution prospective trial
Authors: J. P. Collart, M. Barette, A. S. Cardinael, J. M. Mine, E. Salmin, M. Top, P. Delree, P. Y. Mignolet, L. D'Hondt, J. L. Canon
Journal: Journal of Clinical Oncology (2004)

9689 Background: Despite numerous studies emphasizing the value of SNB in staging breast cancer (BC), this technique has not yet become a standard of care. The long recommended « learning curve », restricts the technique to a few expert surgeons and limits its widespread use. Methods: 118 successive BC patients were offered to undergo SNB prior to classical axillary dissection. 99mTc-nanocolloïds were peritumorally injected by a nuclear medicine (NM) physician or by a radiologist for non palpable tumors. Dynamic and serial scintigraphic views were acquired to pinpoint the sentinel node (SN). Orthogonal SN projections were marked on the skin. A NM physician was present in the operating room for at least the first five procedures (and thereafter as often as possible) to train the surgeon to correctly use the scintigraphic views, the skin marks and the gammaprobe. Serial slices of SN and non SN were histologically analysed with HES staining. SN were also immunostained with a cytokeratin (CK) marker (CAM 5.2). Each case was discussed in a weekly multidisciplinary meeting. NM staff was responsible for coordination. Results: 15 different surgeons were involved in the study. The median number of procedures/surgeon was 10 (1–29). Among the 118 patients, SN could not be identified by scintigraphy in 6 patients (5%) and during the surgical procedure in 12/112 patients (11%). Either SN or non SN were not available in 9 additional patients. Among the 91 procedures for which SN and non SN were both available, a single SN was identified in 48 (53%), 2 in 20 (22%) and greater than 2 in the others. The median number of non SN removed was 7 (1–37). False negative rate (HES and CK negative SN/positive non SN) was 3/39 (7.7%) for unselected tumors and 0/21 (0%) for unifocal ≤ 20 mm tumors. Staging was upgraded in 7/91 (7%) due to CK. The SN was the only positive node in 28/36 patients (78%).Conclusions: Our results are comparable to those obtained by teams using a limited number of BC-dedicated surgeons . This study shows that more numerous non-BC-dedicated surgeons can also successfully use the technique, as long as they work under the control of an integrated multidiscilinary team. No significant financial relationships to disclose.
Phase II study of 3'-deoxy-3'-18F fluorothymidine PET/CT (FLT-PET) in the assessment of early response in locally advanced breast cancer (LABC): Preliminary results of ACRIN 6688.
Authors: Lale Kostakoglu, Fenghai Duan, Michael O Idowu, Paul R Jolles, Harry Douglas Bear, Mark Muzi, Jean Cormack, Daniel A. Pryma, Jennifer M. Specht, Linda Hovanessian Larsen, John Miliziano, Sharon Mallett, Anthony Frank Shields, David A. Mankoff
Journal: Journal of Clinical Oncology (2014)

526 Background: FLT-PET imaging can be exploited as a marker of cellular proliferation and tumor (tm) therapy response. Our primary objective was to determine if early change in tm FLT uptake predicts pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in primary tms in LABC pts. The secondary objective was to correlate standardized uptake values (SUVmax) with Ki-67 at baseline and after NAC. Methods: In this phase II study, 51 LABC pts [stage IIA-IIIC] were evaluable for primary objective analysis. NAC was according to standard of care; imaging was not used to change management. All 51 pts underwent FLT-PET imaging at baseline (FLT-1), and after one cycle (FLT-2);43 pts were imaged post-NAC (FLT-3). SUVmax's were averaged for multiple primary tms. The percent change in SUVmax (ΔSUVmax) between FLT-1 and FLT-2 was calculated. Pathologic response, Ki-67 assay and PET/CT were assessed at core labs. The predictive value of ΔSUVmax for pCR was determined by ROC; by area under the curve (AUC). Correlation between SUVmax and Ki-67 was assessed by the Spearman coefficient (R). Results: A pCR was achieved in 9 of 51 pts. At FLT-1, primary tm SUVmax range:0.9-11.8. FLT-1 uptake was not different between pts with pCR and non-pCR (p=0.59). NAC led to a significant ΔSUVmax (mean,36%;95%CI 28%-45%). AUC for ΔSUVmax in the prediction of pCR=0.68 [95%CI 48%-86%]. The best ΔSUVmax cut-off for predicting pCR was 51% (sensitivity 56%;specificity 79%). The difference in ΔSUVmax between pts with and without pCR was significant (20%;one-sided p=0.045). The correlation between FLT-1 SUVmax and Ki-67 was weak (R,0.29, p=0.04) but stronger at FLT-3 (R, 0.67%, p<0.0001). Conclusions: There was a significant difference in FLT ΔSUVmax in responders vs. non-responders after one NAC cycle, and FLT-PET was marginally predictive of pCR despite variable therapy. Post-NAC FLT uptake correlated with Ki-67. These data suggest that further work is warranted to define the clinical utility of FLT-PET in early evaluation of LABC therapy response. This project was funded in part with funds from the Department of Health & Human Services (DHHS);Grant#CA80098. Clinical trial information: NCT00572728.
Patterns of surveillance after curative intent surgery in elderly stage I-IIIA non-small cell lung cancer patients.
Authors: Christine Agnes Ciunci, Nandita Mitra, Lin Yang, Corey J. Langer, Angela DeMichele, Andrew J Epstein, Anil Vachani
Journal: Journal of Clinical Oncology (2014)

7541 Background: The optimal strategy for imaging surveillance of stage I-IIIA non-small cell lung cancer (NSCLC) patients (pts) after curative intent surgery is unknown. In general, current guidelines recommend imaging with chest CT every 6-12 months for the first 2 years, then annually. In the absence of strong evidence to implement guidelines, variability in imaging has been noted in limited survey data. There are no population studies identifying how pts are being followed in practice. Methods: We performed an observational retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER)-Medicare database to determine the primary surveillance modality, either chest CT or chest x-ray (CXR), in elderly stage I-IIIA NSCLC pts who underwent lobectomy or pneumonectomy. We defined the primary modality as CT for pts undergoing at least 1 CT in both years 1 and 2 of surveillance, and as CXR for pts who did not fit the CT criteria, and who had at least 2 CXR’s in both years 1 and 2 of surveillance. Results: 10,959pts were identified as undergoing curative intent surgery, of whom 94% had lobectomy and 6% had pneumonectomy. 58% of pts were ages 65-74, and 42% were 75 or older. 50% of pts were female. 70%, 16% and 14% of pts were stage I, II and IIIA respectively. 68% had non-squamous histology and 32% had squamous. 5,714 (52%) pts were followed by CT surveillance, and 2,491 (23%) were followed by CXR. 2,754 (25%) pts did not fit the criteria for either.Despite current guidelines, only 47% of stage I, 63% of stage II, and 66% of stage IIIA pts completed at least 1 CT in both years 1 and 2 after surgery. In this population, as stage and age decreased, surveillance of some sort was used less frequently (p<0.001), and CXR over CT surveillance increased (p<0.001). Pneumonectomy pts were more likely than lobectomy pts to have surveillance (p=0.002). Conclusions: This is the first population-based study to characterize the patterns of surveillance after curative intent surgery in elderly NSCLC pts. More evidence is needed to evaluate the effectiveness of different surveillance strategies to better shape guidelines and practice.
The role of CHFR as a predictive marker of response to taxane-based preoperative chemotherapy in triple-negative breast cancer.
Authors: Elisavet Paplomata, Gabriel Sica, Shahrzad Ehdaivand, Dana Nickleach, Yuan Liu, Amelia Bruce Zelnak, Ruth O'Regan, Johann Christoph Brandes
Journal: Journal of Clinical Oncology (2014)

1112 Background: Taxanes are frequently used in the treatment of breast cancer. CHFR (checkpoint with forkhead and ringfinger domains) is a novel biomarker of resistance to microtubule targeting agents that can help individualize care and identify targets for overcoming this resistance. Our institution showed that high CHFR is associated with decreased response to taxanes and worse overall survival in patients with lung cancer. The current work evaluated the translational significance of CHFR in breast cancer. Methods: We studied a cohort of patients with triple negative breast cancer (TNBC), who were treated with pre-operative taxane-based chemotherapy followed by surgery. Archived paraffin-embedded tissue was stained for CHFR using immunohistochemistry. The level of protein expression was assessed by light microscopy and scored for intensity of staining and percentage of staining cells. CHFR expression was associated with pathologic complete response (pCR) and progression free survival (PFS). Covariates included age, race, stage, grade, tumor size, lymph node involvement, and type of chemotherapy. The univariate association with pCR was assessed using the chi-square test or Fisher’s exact test, where appropriate for categorical covariates; and ANOVA for numerical covariates. The univariate and multivariate association with PFS was assessed using the Cox proportional hazard model. Results: We analyzed tumor samples from 43 eligible patients, with median age of 57 years. 27.9% of patients achieved a pCR. 88.4% of patients had high CHFR expression. The expression of CHFR was not associated with clinical outcomes: pCR rate or PFS. All analyses were repeated on 30 patients treated with doxorubicin/cyclophosphamide and paclitaxel; the high expression of CHFR still did not have a statistically significant association with pCR or PFS though there was a marginal trend towards better PFS. Conclusions: In this cohort of TNBC patients, the majority of tumors had high CHFR expression. This did not associate with clinical outcomes: pCR and PFS. We hypothesize that TNBC may be characterized by high CHFR; evaluation of hormone receptor positive and HER2 positive tumors may be worth exploring.
Advantages of a Truly Open-Access Data-Sharing Model
Authors: Monica M. Bertagnolli, Oliver Sartor, Bruce A. Chabner, Mace L. Rothenberg, Sean Khozin, Charles Hugh-Jones, David M. Reese, Martin J. Murphy
Journal: New England Journal of Medicine (2017)

There are many models for sharing clinical-trial data. These investigators provide their viewpoint on why an open-data model has value over others.
Simian Virus 40 DNA sequences in non-Hodgkin's lymphoma
Authors: F. Samaniego, S. Wang, D. Young, L. Fayad, S. Wang
Journal: Journal of Clinical Oncology (2004)

6604 Background: There are no recognized etiologic factors for most Non-Hodgkin's lymphoma (NHL), which has an incidence and death rate that has doubled since 1970. Simian virus (SV) 40 infects human cells and has been shown to confer potent cell transforming properties. Recent studies have made an association of SV40 DNA with NHL. However, data is lacking on expression of viral genes. To answer this question, we analyzed NHL for the presence of SV40 large T antigen (T-ag) DNA and protein. Methods: Genomic DNA was isolated from formalin-fixed NHL tumors and examined for SV40 DNA sequences by PCR amplication of the N-terminus of T-ag using oligomers PYVfor and PYVrev. Tumor DNA was first tested for quality by amplification of the β-actin gene and only those samples that supported amplification were used for further analysis. To assess for SV40 protein expression, NHL tumor sections were stained using antibody (Pab108) targeting T-ag. Results: 70 NHL tumors were PCR amplified for the SV40 T-ag. 36 of 70 NHL tumors were found to generate a product for SV40 DNA. Control negative DNA samples gave consistently negative results and DNA from formalin-fixed tumors induced by COS1 cells produced consistent positive results in this analysis. 7 of 7 NHL PCR products were sequenced and all 7 were identified as being SV40 DNA similar to wild type SV40 strain 776. Laboratory stations dedicated for DNA isolation, storage, and PCR mixing were monitored and did not have SV40 DNA, indicating that tumor DNA was the only source of SV40 DNA. 28 of 57 NHL tumors showed cellular localization of anti-T-ag antibody, mostly cytoplasmic staining and 20 NHL tumors were positive for SV40 DNA by PCR. Tumor sections of COS1 cell-induced tumors showed over 10% of cells were positive for T-ag with a nuclear distribution. 20. Conclusions: This report finds SV40 DNA sequences and T-ag epitopes in NHL. No significant financial relationships to disclose.
Effect of food on the pharmacokinetics (PK) of olaparib after oral dosing of the capsule formulation.
Authors: Ignace Vergote, Annemie Rutten, Christian D. Rolfo, Patricia M.M.B. Soetekouw, Sarah Slater, Henk M.W. Verheul, Helen Swaisland, Anitra Fielding, Karen So, Sally Garnett, Malcolm Ranson
Journal: Journal of Clinical Oncology (2014)

2599 Background: The oral PARP inhibitor olaparib is well tolerated at doses ≤400 mg bid (capsule formulation) and has shown efficacy in patients (pts) with BRCA-mutated ovarian cancer (Ledermann et al ASCO 2013). This is the first study to evaluate the effect of food on olaparib PK. Methods: InPart A of this open-label, randomized, crossover Phase I trial (NCT01851265), adult pts with refractory/resistant advanced solid tumors received a single oral dose of olaparib 400 mg (8 x 50 mg capsules) in each of 3 prandial states, after (1) an overnight fast (2) a high-fat meal and (3) a standard meal (5–14 days’ washout between doses). Blood samples were taken pre-dose and regularly up to 72 h post-dose. Part B was an extension phase to further evaluate safety, where pts completing Part A could receive continuous dosing with olaparib 400 mg bid (capsules) whilst deriving clinical benefit. AE data were collected in both phases. Results: 32 pts (ECOG PS 0/1: n=30; PS 2: n=2) entered the study (female, 84%; median age, 59.5 y; most common tumor types, ovarian [44%], breast [19%], rectal [13%]). 30 pts contributed to statistical analysis (2 pts were excluded: n=1, previous gastric surgery; n=1, withdrawal after first dose [grade 1 vomiting]). The effect of food was similar for both meals. The rate of absorption was slower in the presence of food (tmax delayed by ~2 h) resulting in little impact on Cmax whilst the extent of absorption (AUC) was increased by ~20% in the fed state. AE data from Part A were consistent with the known safety profile of olaparib. Part B is ongoing. Conclusions: The PK of olaparib following oral dosing of the capsule formulation is affected by food. Olaparib capsule doses should be taken on an empty stomach. Clinical trial information: NCT01851265. PK parameter Fed Glsmean (n) Fasted Glsmean (n) Glsmean ratio (fed:fasted) 90% CI for Glsmean ratio High-fat meal Cmax (µg/ml) AUC (µg.h/ml) tmax (h) 6.2 (27) 69.6 (27) 4.03 (27)* 6.2 (30) 58.0 (29) 1.72 (30)* 1.01 1.20 2.79† 0.93 – 1.10 1.09 – 1.32 2.24 – 3.50† Standard meal Cmax (µg/ml) AUC (µg.h/ml) tmax (h) 6.7 (29) 69.2 (27) 4.00 (29)* 6.2 (30) 58.0 (29) 1.72 (30)* 1.09 1.19 2.00† 1.01 – 1.19 1.08 – 1.32 1.53 – 2.40† Abbreviations: Glsmean, geometric least squares mean. *Median. †Median of food effect and 90% CIs, calculated using the Hodges–Lehmann estimator.
Proof-of-concept study of Sym004, an anti-EGFR monoclonal antibody (mAb) mixture, in patients (pts) with anti-EGFR mab-refractory KRAS wild-type (wt) metastatic colorectal cancer (mCRC).
Authors: Rodrigo Dienstmann, Josep Tabernero, Eric Van Cutsem, Andres Cervantes-Ruiperez, Susana Rosello Keranen, Marta Benavent Viñuales, Ida Kjær, Mikkel W Pedersen, Niels Jorgen Ostergaard Skartved, Mimi F Flensburg, Ivan David Horak, Rocio Garcia-Carbonero
Journal: Journal of Clinical Oncology (2013)

3551 Background: KRAS wt mCRC pts progressing on chemotherapy and anti-EGFR mAbs have limited treatment options. Sym004 is a first-in-class drug mixture of two mAbs targeting non-overlapping epitopes on the EGFR, causing its internalization and degradation. With this unique mechanism of action, Sym004 overcomes acquired resistance to anti-EGFR mAbs in preclinical studies. Methods: Open-label, multicenter trial assessing safety (primary endpoint) and efficacy of 2 dose levels of Sym004 in KRAS wt mCRC pts with prior clinical benefit to anti-EGFR mAbs and subsequent progression during or within 6 months after treatment cessation. Sym004 was administered until disease progression or unacceptable toxicity. Tumor responses were evaluated centrally according to RECIST criteria. Paired skin and tumor biopsies were obtained at baseline and week 4. Results: In total, 42 pts were enrolled at 9 mg/kg (13) and 12 mg/kg (29). Median age was 66 years and median number of prior treatment lines 3. Central radiology review was performed in 12/13 (92%) pts at 9 mg/kg and 27/29 (93%) pts at 12 mg/kg. Tumor shrinkage &gt; 10% was documented in 4/12 (33%) pts at 9 mg/kg, with partial response (PR) in 1/12 (8%) and stable disease (SD) in 9/12 (75%). At 12 mg/kg, 7/27 (26%) pts had &gt; 10% tumor shrinkage, with PR in 3/27 (11%) and SD in 15/27 (56%). Median progression-free survival was 13.6 weeks (95% CI: 5.3-23) and 13.7 weeks (95% CI: 5.9-18.6), respectively. Duration of response for pts with PR was 5.6-17.6 weeks. Grade 3 or higher toxicity included skin rash in 26/42 (62%), hypomagnesemia in 16/42 (38%) and diarrhea in 2/42 (8%). Adverse events were manageable with dose reduction and supportive medication. There were no indications of immunogenicity. Pharmacodynamic analysis in serial tumor samples showed profound down-regulation of EGFR and reduction in proliferation marker Ki67. Conclusions: Sym004 at weekly doses of 9 and 12 mg/kg showed significant clinical activity in anti-EGFR treatment-refractory KRAS wt mCRC pts, clearly demonstrating proof-of-concept. Serial biopsies confirmed its mechanism of action. No unexpected adverse events were observed. Clinical trial information: NCT01117428.
Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice
Authors: Aubrey C. Chan, Stavros G. Drakos, Oscar E. Ruiz, Alexandra C.H. Smith, Christopher C. Gibson, Jing Ling, Samuel F. Passi, Amber N. Stratman, Anastasia Sacharidou, M. Patricia Revelo, Allie H. Grossmann, Nikolaos A. Diakos, George E. Davis, Mark M. Metzstein, Kevin J. Whitehead, Dean Y. Li
Journal: Journal of Clinical Investigation (2012)

The control data provided in Figure 7, E, F, andG, were inadvertently provided from incorrectly matched samples.
High-Dose Cytarabine (HiDAC) Improves the Cure Rate of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML): Is It Better to be Given As Induction Therapy or As Consolidation Therapy?
Authors: Anthony P Schwarer, Joel Wight, Kathryn Jackson, Ashanka Mahilal Beligaswatte, Jason P Butler, Glen Kennedy, Louisa Martin, Ian D. Lewis, Devendra Hiwase, Daniela Zantomio, Simon Z. He, Andrew Grigg, Kirk Morris, Peter Mollee, Paula Marlton
Journal: Blood (2016)
Preoperative chemoradiation therapy for localized retroperitoneal sarcoma (RPS): Final results of a phase II study from the Italian Sarcoma Group.
Authors: Alessandro Gronchi, Antonino De Paoli, Carla Dani, Domenico Franco Merlo, Vittorio Quagliuolo, Giovanni Grignani, Giulio Bertola, Piera Navarria, Claudia Sangalli, Angelo Paolo Dei Tos, Marco Fiore, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2013)

10519 Background: To study the feasibility, safety and activity of the combination of high dose long-infusion Ifosfamide (HLI) and radiation therapy (RT) as preoperative treatment for resectable localized RPS. Methods: Patients received 3 cycles of HLI (14 g/m 2 ). RT was started in combination with the onset of the 2 nd cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. Primary end-point was 3-yr relapse free survival (RFS). The expected 3-yr RFS in the study population treated with surgery alone was 40%. The experimental treatment was aimed at achieving a relative reduction in relapses of at least 1/3, corresponding to a 3-yrs RFS of 55%. With 60 enrolled patients, the study would have had a 90% power to discriminate between the hypotheses of 3-yrs RFS of 40% (H0) and 55% (H1), using a 1-sided 10% level of significance. Results: Between December 2003 and 2010, 86 patients were recruited. 3 patients were ineligible after central pathological review. 63 were affected by primary tumor and 20 by local recurrence. The 3 main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%) and leiomyosarcoma (14/83, 17%). Median tumor size was 120 mm (IQ range= 82-160). The overall preoperative treatment was completed in 60 patients. CT was completed in 65 patients, while RT in 73. Five patients had progression before surgery (3 distant and 2 local) and were not operated. 78 patients underwent surgery. At a median follow-up of 4.8 years (IQ range=3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM) respectively; 30 patients died of disease. 3-yr and 5-yr RFS and overall survival were 56% and 44%, and 74% and 59%, respectively. Crude cumulative incidence of LR and DM at 5 yrs were 37% and 26%, respectively. Conclusions: The combination of preoperative HLI and RT was feasible in two thirds of patients, while pre-operative RT could be completed in most (73/83). The primary endpoint of the study was met. Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international Phase III trial is exploring the role of RT alone. Clinical trial information: ITASARC_*II_2004_003.