tbuckley/cabot-search huggingface dataset:
Clinical use of the 21-gene assay and patient experiences in early-stage breast cancer.
Authors: Steven J. Katz, Christopher Ryan Friese, Yun Li, Dennis Deapen, Ann S. Hamilton, Kevin C. Ward, Allison W. Kurian
Journal: Journal of Clinical Oncology (2016)

6501 Background: The 21-gene assay enables oncologists to tailor chemotherapy in early-stage, estrogen-receptor positive breast cancer. Few studies have studied the impact of test results on chemotherapy recommendations and receipt, and on patient experiences. Methods: We surveyed 3781 women with breast cancer treated in 2013-14 selected by the Georgia and Los Angeles SEER Registries (response n= 2593, 69%). Women reported their oncologist’s recommendations, chemotherapy receipt, and treatment decision satisfaction. SEER registries linked Genomic Health, Inc test results to patients. We selected 1287 patients with Stage I/II, ER+, HER2- disease and categorized them into 3 groups 1) node-negative favorable (no high-risk features); 2) node-negative, less favorable (age at diagnosis < 50 yrs or Grade 3 tumor); and 3) node-positive. Regression models - adjusted for comorbidity, education, income, race, location, and sampling design - examined test scores and clinical factors on chemotherapy recommendation and receipt. Those tested rated their satisfaction on a 5-point Likert scale (1=not satisfied, 5=totally satisfied). Results: Overall 53% of selected women were tested (57%, 65%, and 31%, for groups 1, 2, & 3). Recommendations for chemotherapy and chemotherapy receipt were consistent with risk scores (Table), and racial differences were not significant in regression models. Most (82%) tested patients reported that the test helped decision making yet 14% did not recall their test status. The x̅(SD) testing satisfaction score was 4.6(0.7). Conclusions: Oncologists personalize treatment based on assay results, even in node-positive disease. High satisfaction and absence of disparities suggests that precision medicine advances have improved the quality of systemic breast cancer treatment. Node-neg, favorable (n=718) Node-neg, unfavorable (n=283) Node pos (n=286) Recommended Against/ Neutral/For Got Chemo Recommended Against/ Neutral/For Got Chemo Recommended Against/Neutral/For Got Chemo No test (n=608) 54 / 21 / 25 14 25 / 9 / 66 59 9 / 9 / 82 83 RS 0-17 (n=427) 78 / 10 / 12 3 64 / 11 / 25 6 49 / 12 / 39 22 18-30 (n=204) 38 / 19 / 43 38 20 / 25 / 55 52 9 / 22 / 69 64 >30 (n=48) 0 / 0 / 100 100 3 / 5 / 92 94 0 / 0 / 100 100 %s reported. RS: Recurrence Score
A metabolomic signature for predicting chemosensitivity in gastric cancer.
Authors: Francisco José García Verdejo, Ana Laura Ortega Granados, Caridad Díaz Navarro, Natalia Luque Caro, David Fernández Garay, Maria Carmen Álamo de la Gala, María Ruiz Sanjuan, Capilla de la Torre Cabrera, Mónica Fernández Navarro, Rosario Dueñas García, Victor Navarro Pérez, Esther Martínez Ortega, Nuria Cárdenas Quesada, Ana Jaén Morago, Yessica Plata Fernández, Francisca Vicente Pérez, Olga Genilloud, Ana María Lozano Barriuso, Pedro Sanchez Rovira, Jose Pérez del Palacio
Journal: Journal of Clinical Oncology (2017)

e15504 Background: Perioperative chemotherapy (QT) with platinum and fluoropyrimidines with or without anthracyclines is recommended option in patients with resectable gastric cancer (GC) at least cT2 or nodal involvement. Another option is surgery followed by QT with radiotherapy (QT/RT) or QT without RT in patients with D2 lymphadenectomy. Unfortunately, a considerable percentage of patients progress during neoadjuvant-QT (neo-QT) and some cases become inoperable cancer. These patients could benefit from curative surgery after diagnosis without neo-QT. Currently, histological/molecular markers have not been established to predict which patients can benefit from neo-QT. As potent analysis method, study of blood metabolites of resectable GC patients to establish a profile to differentiate responder patients (R-P) or not-responder (NR-P) to neoadjuvant-QT is promising. To establish a metabolomic profile or metabolomic signature and correlate with chemosensitivity, defined as pathological and clinical response is our endpoint. Methods: To this end we performend an untargeted metabolomic analysis by LC-HRMS of serum samples from resectable GC patients before neo-QT (n = 20 vs n = 10 healthy controls). Chemosensitive tumors were defined as those with good pathological response (Mandard 1 or 2) and partial response by TAC and chemoresistance tumors, defined as those with poor pathological response (Mandard 5) or/and progression by TAC. Reverse phase and HILIC chromatographic modes were applied to deal with highly polar as well as hydrophobic as required for untargeted metabolomics. For identification of potential biomarkers, we used in combination 2 independent variable selection techniques: principal component analysis and Student t test. Results: 11 patients were R-P and 9 patients were NR-P. We observed differences in metabolic profile between patients with GC &amp; healthy controls and R-P &amp; NR-P to neo-QT. Seven identified metabolites contributed most to the differentiating between R-P and NR-P. Conclusions: There are different metabolomic phenotypes among patients R-P and NR-P to neo-QT. It is necessary to validate a metabolomic signature to allow effective chemosensitivity prediction in patients with resectable GC.
Cochrane director’s expulsion results in four board members resigning
Authors: Nigel Hawkes
Journal: BMJ (2018)

The Cochrane Collaboration’s governing board has voted to expel one of its most prominent members, Peter Gotzsche, provoking the resignation of four other board members who backed him.

Gotzsche, director of the Nordic Cochrane Centre, is well known for his outspoken criticisms of breast cancer screening and the overuse of psychiatric drugs. His sacking came after a heated meeting of the governing board in Edinburgh on Thursday13 September as the organisation prepared for its annual meeting.

Maryanne Demasi, an Australian television journalist and ally of Gotzsche, said in a blog post that he was given five minutes at the meeting to respond to a report by an external law firm commissioned by the board to review a growing dispute between him and Cochrane’s chief executive, Mark Wilson, who is backed by other trustees.1

At issue was the claim that Gotzsche had overstepped the mark by using the Cochrane name …
Evaluation of whole body MRI for early detection of cancer in TP53 mutation carriers: Final results of the LIFSCREEN study.
Authors: Olivier Caron, Karamouza Eleni, Stéphanie Foulon, Patrick Benusiglio, Valerie Bonadona, Laurence Faivre, Christine M Maugard, Catherine Dugast, Emmanuelle Barouk-Simonet, Capucine Delnatte, Yves-Jean Bignon, François Eisinger, Nathalie Chabbert-Buffet, Viviane Feillel, Pascal Pujol, Katty Malekzadeh, Corinne Balleyguier, Leonor Fasse, Thierry Frébourg, Laurence Brugieres
Journal: Journal of Clinical Oncology (2018)

1527 Background: Li Fraumeni syndrome (LFS) is a rare cancer predisposition caused by TP53 germline mutation associated with a broad tumor spectrum making surveillance very complex. Whole body MRI (WBMRI) is an attractive strategy. The LIFSCREEN nation-wide trial was designed to evaluate the impact of adding WBMRI as a screening tool on the overall survival (OS) of LFS patients. Methods: Participants (pts) were TP53 mutation carriers, > 5 and < 71 y, with/without cancer personal history. Pt were randomized in standard surveillance arm (“A”: clinical exam, brain MRI, abdomino-pelvic US, CBC, and breast MRI/US and breast US for women over 20), or in “B” arm (A + WB diffusion MRI). Each pt repeated annually the process for at least 3 years. Acceptability and psychological impact were evaluated throughout the study. Results: 105 pts (mean age 33y [5-67]) were randomized in one of the 19 French centers. In 318 screening rounds, 24 pts presented 31 new primary cancers (NPC): 20 in A arm and 11 in B arm. 12 NPC were diagnosed at the first round. Cancer-free survival (NPC and relapses) was similar at 3 years in both arm (p = 0.23). 27 Biopsies were carried out in A arm and 20 in B arm. 157 WBMRI were performed, with a sensitivity and specificity of 0,8 and 0,89, respectively (10% false positive ). Their centralized review showed a 31% discordance rate (44/141). The 3 years OS was 90% [81-95], with no difference between the 2 arms (p = 0.58). The 3- years OS with NPC was 54.8% [32-75]. 10 pts voluntarily left the study. Psychological impact was similar in both arms, with low screening-related distress. Conclusions: This first randomized study performed on one of the largest TP53 carrier series did not show WBMRI efficiency on OS. Nevertheless, it displayed correct sensitivity and specificity, with few biopsy generation. Long-term follow-up was acceptable and feasible in each participating center. Despite its tricky interpretation, WBMRI was the only modality to detect lung cancer, whose incidence was surprisingly high. TP53 mutation carrier surveillance might be completed with WBMRI, in a multimodality setting. The very high short-term mortality in pt with new cancer makes prevention and treatments improvement mandatory. Clinical trial information: NCT01464086.
TCT-429 A Randomized Trial Comparing a Novel Sirolimus-Eluting Bioresorbable Scaffold withEverolimus-Eluting Metallic Stents in Patients With Coronary Artery Disease: Two-year Clinical Outcomes
Authors: Yaling Han, Guosheng Fu, xiaozeng Wang, Kai Xu, Bo Xu
Journal: Journal of the American College of Cardiology (2018)
Extended neoadjuvant chemotherapy (CT) in borderline resectable pancreatic cancer (BRPC): Updated results.
Authors: Zaheer S. Kanji, Flavio G Rocha, Alicia M Edwards, Margaret T. Mandelson, Bruce S. Lin, Richard A. Kozarek, J. Bart B. Rose, Thomas R Biehl, Adnan Alseidi, Scott Helton, Vincent J. Picozzi
Journal: Journal of Clinical Oncology (2017)

e15771 Background: Optimum therapy (Rx) for BRPC is unknown. Since 2008, we have used neoadjuvant Rx with extended course chemotherapy (CT) but not routine neoadjuvant chemoradiation (CRT). Initial results were presented in 2013 (Rose et.al. J Clin Oncolabstr 4043). We present updated findings here. Methods: Patients (pts) were prospectively identified in our institutional PC database. Inclusion criteria: 1) bx-proven PC; 2) radiographic staging per AHPBA/NCCN criteria; 3) no prior Rx; 4) negative staging laparoscopy whenever feasible; 5) all neoadjuvant Rx at our institution, 6) followup ≥ 24 weeks (wks) from initial Rx . Unless disease progression or Rx intolerance noted, pts received gemcitabine/docetaxel (G/D) as neoadjuvant CT x 24 weeks . At that time, all pts felt likely to achieve R0 resection offered surgery; other pts offered 5FU –based CRT if medically fit. Results evaluated by "intent to treat". Results: Among 129 pts, characteristics include median age 66 yrs (range 33-88 yrs), ECOG PS 0/1/2+ 86/36/7, 97%/43% venous /arterial involvement. 78% (101/129) pts completed ≥80% intended CT; 38% (6/16) pts age &gt; 80 and /or ECOG 2+ (p &lt; 0.01) 51% (66/129) pts were resected (44 R0, 22 R1 ≤ 1 mm margin ). 49% (63/129) pts were not (24 disease progression, 17 surgeon decision (anatomy/safety), 11 Rx toxicity/ comorbidity, 6 unresectable at surgery, 5 pt withdrawal). 45% (31/66) and 23% (16/66) resected pts received postop CRT/CT respectively. Median f/u is 47 months (mo). 58% (38/66) resected pts recurred: 18% (12/66) local, 41% (27/66) systemic. For resected pts, median PFS is 25.0 (95% CI: 16.2-32.7) mo, median OS is 37.6 (95% CI: 27.4-58.5) mo. 5-yr OS is 28% ( 95% CI :14-44%). Median OS for non-resected pts is 13.1 (95% CI 10.9-16.9) mo .Median OS for all pts is 22.1 (95% CI: 18.7-28.4) mo. Conclusions: 1.Our series is distinctive with respect to size, use of laparoscopic staging and neoadjuvant G/D CT as standards,and median f/u 2. Pt selection is key; e.g.approach suboptimal for pts &gt; 80 yrs/ ECOG PS 2+ 3. Reported OS compares favorably with other BRPC and de novo resectable PC cooperative group results 4. Detailed analysis of our study (e.g. prognostic factors) will aid future clinical research in BRPC.
Financial toxicity in a large cohort of thyroid cancer patients: An analysis from the North American Thyroid Cancer Survivorship study.
Authors: Jonas A. De Souza, Raymon Grogan, Sheetal Mehta Kircher, Brisa Aschebrook-Kilfoy
Journal: Journal of Clinical Oncology (2016)

e18284 Background: Financial toxicity (FTox) has been associated with worse health-related quality-of-life (HRQoL), compliance, and survival in cancer patients (pts). Measuring FTox and understanding its predictors are of paramount importance when planning intervention strategies, the value of care, and healthcare policies. We report FTox and its predictors in a large cohort of thyroid cancer pts and survivors. Methods: Pts with thyroid cancer were surveyed in the North American Thyroid Cancer Survivorship Study. FTox was assessed by the validated COmprehensive Score for financial Toxicity (COST), as well as by questions related to financial distress (out-of-pocket costs, loss of income and bankruptcy). Data on sociodemographics, income, type of disease, length of diagnosis (LOD), and prior therapies were collected. Predictors of FTox were assessed in multivariate analyses, controlling for potential confounders, such as HRQoL (as measured by the thyroid cancer-specific City of Hope instrument), and LOD. Results: 581 pts with thyroid cancer within the past 6 years were surveyed in 2 countries: 543 (93.5%) in the United States (U.S.), and 38 (6.5%) in Canada. Most were women (n = 518 pts, 88%). The median LOD was 857 days (range 105-2176 days), and 430 pts (72.8%) had papillary thyroid cancer. There were 51 pts (9%) with Stage IV, and 11 (1.9%) were on tyrosine kinase inhibitors. Overall, 234 pts (39.5%) stated that their out-of-pocket costs were higher than previously thought; 207 pts (35%) felt their disease resulted in loss of income; 44 pts (7.4%) were unable to meet their monthly expenses; and 7 pts (1.2%) declared bankruptcy after diagnosis. The median COST value was 24 (range 0-44). In multivariate analyses, the independent predictors of worse FTox were lower income (p < 0.001), female gender (p = 0.01), lower educational level (p = 0.002), healthcare delivery in the U.S., (p = 0.002), and worse HRQoL (p < 0.001). Conclusions: A significant proportion of pts experience FTox in this large cohort of thyroid cancer survivors. We identified pts characteristics (gender, education, income), as well as geographical differences (healthcare delivery in the U.S.) as predictors of FTox.
ACNS1221: A phase II study for the treatment of non metastatic desmoplastic medulloblastoma in children less than 4 years of age—A report from the Children Oncology Group.
Authors: Lucie Lafay-Cousin, Eric Bouffet, Arzu Onar-Thomas, Catherine A Billups, Cynthia Hawkins, Charles Eberhart, Craig Horbinski, Giles W. Robinson, Douglas R. Strother, Linda Heier, Mark M. Souweidane, Maryam Fouladi, Amar J. Gajjar
Journal: Journal of Clinical Oncology (2017)

10505 Background: Nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity (ND/MBEN) have been associated with a more favorable outcome in younger children. However, treatment-related neurotoxicity remains a significant concern in this vulnerable group of patients. Methods: We prospectively conducted a single-arm multicenter trial of conventional chemotherapy for non-metastatic ND/MBEN, based on a modified HIT SKK2000 regimen excluding the use of intraventricular methotrexate (MTX) injection, with the aim to achieve a similar outcome with reduced treatment related neurotoxicity. The design required 37 patients and targeted a 2-year PFS of ≥ 90%. Secondary objectives included evaluation of feasibility of timely central pathology review, prospective evaluation of the cohort’s molecular profile and neurocognitive outcomes. Results: Between 12/2013 and 07/2016, 26 patients were enrolled, including 16 males and 10 females, diagnosed at a median age of 19.7 months (7.1-42.9 months). Four patients had residual disease at baseline. There were 19 ND and 7 MBEN medulloblastoma, confirmed by central pathology review. All cases were reviewed within 10 days by at least 2 of the 3 neuropathologists. The study was closed early following interim analysis due to a higher than expected relapse rate. At last follow-up, 7 patients had relapsed (3 local, 2 distant and 2 combined) at a median time of 9.7 months from diagnosis (range, 9.5-13.7 months). One patient subsequently died of disease. The current median follow-up for the 25 survivors is 1 year (range, 0.2-1.9 years) and the 1 year PFS rate is 66.2% (SE 12.2%). Based on the currently available information, older age (p = 0.07) and ND histology (p = 0.009) appear to be associated with worse PFS. To date none of the patients with MBEN histology have relapsed. Conclusions: The proposed modified regimen of chemotherapy without intraventricular MTX failed to achieve the desirable 2 y PFS of 90%, leading to premature closure of the study. Ongoing molecular characterization of the cohort may help uncover patients who may still benefit from this regimen. Clinical trial information: NCT02017964.
Factors impacting progression-free survival (PFS) as a predictor of overall survival (OS).
Authors: David J. Stewart, Dominick Bossé, John Frederick Hilton, Glenwood D. Goss, Michael Fung-Kee-Fung, Derek J. Jonker
Journal: Journal of Clinical Oncology (2018)

6556 Background: Unlike OS hazard ratios (HRs), PFS HRs are unaffected by crossover or post-progression survival, but PFS HRs are poor predictors of OS HRs. We hypothesized that absolute PFS gain (ΔPFS) might predict absolute OS gain (ΔOS). Methods: We assessed 279 randomized solid tumor drug comparisons with ≥200 incurable patients from J Clin Oncol or New Engl J Med, 2007 to June, 2017. We used nonlinear regression analysis of PFS & OS curves to calculate half-lives (t1/2s: time to death or progression in ½ the remaining patients) and to assess if PFS curves fit 2-phase vs only 1-phase decay models. ΔPFS ≥ 1.5 months (m) is a better predictor of ΔOS ≥ 2m if t1/2s are used than if medians are used (Stewart, Proc AACR, 2018 #1644). We used t1/2s from the 149 studies with ΔPFS p < 0.05 to calculate positive and negative predictive value (PPV & NPV) of ΔPFS ≥ 1.5 m as a predictor of ΔOS ≥ 2 m in selected subgroups. PPV = (no. studies with ΔPFS ≥ 1.5 m & ΔOS ≥ 2 m)/ (no. studies with ΔPFS ≥ 1.5 m & any ΔOS). NPV = (no. studies with ΔPFS < 1.5 m & ΔOS < 2 m)/ (no. studies with ΔPFS < 1.5 m & any ΔOS). Results: See table. 4 of 14 ICI trials (29%) and 6 of 265 trials with other drugs (2%) had ΔOS that was both ≥ 2 m & significant (p < 0.05) despite insignificant ΔPFS (p > 0.05). Conclusions: With low CO, ΔPFS that is both significant & greater than 1.5 m predicts ΔOS greater than 2 m. with high PPV and NPV across tumor types other than prostate cancer and across drugs other than ICIs. ICIs (most of which had PFS curve 2-phase decay) generally had high ΔOS despite low ΔPFS. ΔPFS < 1.5 m/ ΔOS < 2 m ΔPFS < 1.5 m/ ΔOS ≥2 m NPV % ΔPFS ≥1.5 m/ ΔOS < 2 m ΔPFS ≥1.5 m/ ΔOS ≥2 m PPV % No. comparisons No. comparisons All 46 7 87 18 78 81 Proportion of studies with crossover < 20% or unknown (Low CO) vs > 20% (High CO) Low CO 31 5 86 10 52 84 High CO 15 2 88 8 26 76 PFS curve for arm with longer PFS: 2 phase decay 5 3 63a 3 17 85 1 phase decay 41 4 91a 15 61 80 Drugs: Chemo: Low CO 7 1 88 4 7 64 High CO 7 1 88 4 7 64 Bevacizumab: Low CO 5 0 100 2 8 80 High CO 1 0 100 3 4 57 Oral angiogenesis inhibitors 8 1 89 0 2 100 Immune check-point inhibitors (ICIs) 1 3 25b 1 5 83 Hormones 0 0 NA 1 8 89 Other monoclonals 4 1 80 0 9 100 Oral targeted drugs 13 1 93 3 23 88 Tumors: Breast 2 1 67 2 19 90 Colon 10 1 91 2 11 85 NSCLC 13 2 87 2 11 85 Melanoma 0 3c 0 1 8 89 Prostate 1 0 100 4 5 56b a. P = 0.06b. P = 0.02 vs all othersc. all with ICIs
Circulating tumor DNA analysis for outcome prediction in localized esophageal cancer.
Authors: Tej D. Azad, Aadel Chaudhuri, Aaron M. Newman, Henning Stehr, Joseph Schroers-Martin, Jacob J. Chabon, Penny Fang, Yawei Qiao, Zhongxing X. Liao, Ritsuko Komaki, Ash A. Alizadeh, Steven H. Lin, Maximilian Diehn
Journal: Journal of Clinical Oncology (2017)

4055 Background: Blood-based biomarkers are not used in routine clinical practice in patients with esophageal carcinomas (ECs). Circulating tumor DNA (ctDNA) is an attractive biomarker that could be applied to ECs. We performed a study to explore pre- and post-treatment ctDNA analysis using the next generation sequencing-based CAPP-Seq method as a prognostic biomarker for localized EC. Methods: We prospectively enrolled 29 patients with localized EC treated with chemoradiotherapy (CRT) between June 2011 and October 2015. 12 (43%) patients were treated with CRT alone and 17 (57%) were treated with CRT followed by esophagectomy. Our cohort included patients with stage IB (1; 3.4%), II (7; 24.1%), and III (21; 72.4%) disease. Eight (27.6%) harbored squamous cell carcinoma (SCC) and 21 (72.4%) adenocarcinoma (AC). All patients received pre-treatment evaluation by thoracic CT, PET/CT, and esophagoduodenoscopy. ctDNA levels were quantitated in pre-treatment and post-treatment plasma samples using CAPP-Seq. Results: Median follow-up time was 21 months. We detected ctDNA pre-treatment in 72.4% of cases (N = 21) with a median concentration of 2.69 haploid genome equivalents per mL (hGE/mL; range 0.34-107.3). Pre-treatment ctDNA concentrations were strongly correlated with metabolic tumor volumes (MTV; R 2 = 0.74; p = 1.7e-07) and were significantly higher in SCC than AC patients (28.2 vs. 2.1 mean hGE/mL; p = 0.002). Overall survival (OS) at 2 years for pretreatment ctDNA+ vs. ctDNA- patients was 47% vs. 86% (HR = 6.0; 95% CI = 0.74-49.2; p &lt; 0.05) and trended toward significance when accounting for stage, histology, and age (p = 0.09). A single post-treatment plasma sample was collected within 3 months of treatment and was available for 19 patients. Post-treatment ctDNA was detected in 3 (15.7%) patients with a median concentration of 11.5 hGE/mL (range 2.2–11.9). Post-treatment ctDNA detection was strongly predictive of poor event-free survival (p &lt; 0.0001) and time to distant metastasis (p &lt; 0.0001). Conclusions: Our data suggest that pre- and post-treatment ctDNA levels may be prognostic for patients with localized EC and could potentially guide risk-adapted adjuvant therapy approaches.