tbuckley/cabot-search huggingface dataset:
Correlation of oncogenic mutations in circulating cell-free DNA (cfDNA) and tumor tissue through a multiplex sequencing platform in patients under consideration for phase I trials.
Authors: Joaquin Mateo, Michael Ong, Lorna Pope, Amy Mulick Cassidy, Timothy Anthony Yap, Geraldine Perkins, Ruth Riisnaes, Penelope Flohr, Khin Thway, Michael Gonzalez, Sadiya Saeed, Anne Mary Young, Helen Nicole Toloui, Khurum Hayat Khan, Kirsty Moran, Matthew Ng, L Rhoda Molife, Udai Banerji, Stanley B. Kaye, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2012)

6 Background: Previous studies suggest that tumoral cfDNA is a potential biomarker in cancer. Methods: Prospective collection of samples from patients (pts) referred to a phase I trials unit, in 2 cohorts: “A”(manual isolation of cfDNA, Sep09-Dec10) and “B”(robotic isolation, Jan11-Sep11) and from 41 healthy volunteers (HV). CfDNA and tumor DNA from matched formalin-fixed paraffin-embedded (FFPE) tissue were isolated, quantified and analyzed for 238 oncogenic mutations (OM) in 19 oncogenes using Sequenom OncoCarta Panel 1.0. Mutation data were used for trial allocation when available. Statistical analyses used Pearson’s Chi-squared test and Mann-Whitney test. Results: 280 pts were included: breast (60; 21%), ovarian (44; 16%), and colorectal (42; 15%). 265 (95%) plasma and 194 (69%) FFPE samples were suitable for analysis. In 181 pts (65%) both samples were available for comparison. Median turnover time for cfDNA 7 days (range 5-14). Median [cfDNA] (concentration; ng/ml) in pts was higher than in HV (“A” 21 v 6.4;p&lt;0.01, “B” 34 v 24;p&lt;0.01). Detection of OM in cfDNA was more frequent when [cfDNA] was above the HV range (67% v 33% p=0.002). Among 181 pts with both samples analyzed, 53 OM were detected in cfDNA, with high concordance with tumor analysis (Table), especially for RAS in colorectal tumors (10/11 91%) and PIK3CAin breast (4/4 100%). In contrast, 29 pts (16%) had OM detected in tumor but not in plasma. The rate of concordance between OM detected in plasma v FFPE was independent of [cfDNA]. 154 pts were enrolled in phase I trials and 26 were given a matched drug according to the mutational analysis. Conclusions: cfDNA may be a useful tool to detect OM in a time frame suitable for clinical decision-making. Concordance of OM found in cfDNA with FFPE samples is high; discordance in this study may be explained by limitations of multiplexed-sequencing techniques, tumor heterogeneity or biologic evolution of the disease. [Table: see text]
Treatment (T) of T2 N0-1 larynx cancer (LC) with hyperfractionated radiotherapy (HRT) and cetuximab (C): Final report.
Authors: R. E. Giglio, A. Navigante, M. D. Pereira, L. Califano, B. M. C. Roth, P. Saco, M. A. Castro, P. Menendez, P. Aguerre, R. Adan, C. Brosio, C. Pogany
Journal: Journal of Clinical Oncology (2011)

5570 Background: Local control rate for T2 LC with HRT alone at our Institution is about 61% and 75-80% with salvage surgery (S) The addition of C to HRT significantly enhanced the local control and survival rates compared to HRT alone with similar toxicity for locally advanced head and neck cancer. C was added to HRT for the treatment of T2N0-1 LC with the primary objective of enhancing local control rate and the secondary objective of extending the time free of laryngectomy (TFL) for T2 LC. Methods: Twenty patients (pts) (19M /1F) with T2 LC were enrolled: 10% had N1, 65% glottic and 35% supraglottic; median age: 65 years. T: HRT was delivered to a total dose of 76.8 Gy in 6.5 weeks. C was delivered at 400 mg/m2 one week before HRT and then 7 weekly doses of 250 mg/m2. Pretreatment evaluation consisted of CT scan and fiberlaryngoscopy (FLC). Toxicity assessment was done weekly. After T pts were evaluated monthly during the first year and then every three months with FLC. All pts signed an informed consent and the trial was approved by the institutional review board and the country’s medical authorities. Results: Compliance: 18/20 pts completed HRT (90%). Median HRT dose: 76.65 Gy. Median HRT duration: 7 weeks. 17/20 pts (85%) received 8 doses of C. Median T duration was 8 weeks. Response: 16/20 pts (80%) achieved a complete response (CR), 3 pts (15%) had persistent disease and all had S and 1 pt had a sudden death not related to T and was not evaluable for response. Five pts with CR recurred at a median time of 10 months (m) (range 6.5-12.3) and had S. At present, with a median follow up of 35 m (r 6.7 – 42.8 m+), 16 pts are alive and disease free (80%) and 10 preserve their larynx (62.5%). Median TFL was 35 m (r 6.7-42.8 m+). Toxicity G3/4 (pts): stomatitis (6); acneiform rash (4); radiation dermatitis (5); dysphagia, diarrhea, vomiting, fatigue, skin infection and pneumonia: (1 each). Six pts were admitted to the hospital due to toxicity. Four pts died: 1 had a sudden death not related to C and 3 due to progressive disease. Conclusions: 1) 85% of the pts received T according to protocol. 2) Local control, disease free survival and TFL rates were higher than the historical ones at our institution, 3) Larynx preservation rate was similar.
Incidental colonic 18F-FDG uptake in gastric cancer patients: Correlation with colonoscopic and histopathologic findings.
Authors: Kyo Young Song, Jung Ho Shim
Journal: Journal of Clinical Oncology (2012)

43 Background: The ability of integrated positron emission tomography and computed axial tomography (PET-CT) to detect synchronous colonic pathology in gastric cancer patients is not fully defined. Methods: Between Jan 2009 and July 2010, total 370 patients diagnosed as primary gastric cancer underwent curative resection in our institution. Among them 147 patients had taken PET-CT and colonoscopy preoperatively. The FDG uptake pattern were reviewed and classified as focal (showed foci of FDG uptake&gt;3.5 SUV max), diffuse (showed FDG uptake&lt;3.5 SUVmax without any foci of uptake) and absent uptake (showed no FDG uptake pattern). Patients with history of known colonic malignancy or colon surgery were excluded. Results: Among the 18 patients who had discovered as focal incidental FDG uptake in colon without any previous colonic pathology, in six patients, has revealed unexpected colonic adenocarcinoma. The mean SUVmax value of focal uptake group(Group A) is 7.3 (±2.3), for those six patients, it was 9.4 (±2.9,p=0.02). And in the diffuse uptake group, most common colonic pathology was tubular adenoma with low grade dysplasia following hyperplastic polyp. The age, gender and primary gastric cancer stage was not differed between the groups. Conclusions: In conclusion, the focal uptake pattern in colon on preoperative PET-CT in gastric cancer patients should be followed by colonoscopy evaluation for incidental significant colonic pathology even colon cancer. However, there was no cut off SUVmax value for the mandatory colonoscopy evaluation based on PET-CT.
Significance of FANCJ expression as a predictive marker of sensitivity to 5-fluorouracil in colorectal cancer.
Authors: R. Nakanishi, H. Kitao, N. Yamashita, N. Kubo, Y. Fujinaka, M. Iimori, E. Oki, M. Morita, Y. Kakeji, Y. Maehara
Journal: Journal of Clinical Oncology (2011)

10618 Background: Fanconi anemia protein, FANCJ, directly interacts with MLH1, a key protein involved in the DNA mismatch repair process. Deficient mismatch repair, or microsatellite instability, is a marker for the ineffectiveness of 5-fluorouracil (5-FU) and positive prognosis of colorectal cancer (CRC). We investigated the significance of FANCJ expression in CRC, focusing on the effects of 5-FU-based adjuvant chemotherapy. Methods: Clinicopathologic features and immunohistochemical expression of FANCJ and MLH1 were studied in 219 patients with CRC. We also analyzed 5-FU sensitivity in CRC cell lines with varying levels of FANCJ expression. Results: FANCJ expression was elevated in tumor tissues compared with normal epithelial tissue (p<0.001). High expression of FANCJ was significantly associated with 5-FU resistance measured by the succinate dehydrogenase inhibition test (p=0.02) and poor recurrence-free survival (RFS) (p=0.03). Among patients with stage II/III tumors who received 5-FU, patients with tumors exhibiting high FANCJ expression had significantly worse RFS than patients with tumors exhibiting low FANCJ expression (p=0.01). Among patients who did not receive adjuvant chemotherapy, FANCJ expression was not correlated with RFS (p=0.76). High FANCJ expression was correlated with 5-FU resistance in tumors with normal MLH1 expression (p=0.01), but not in tumors not expressing MLH1 (p=0.67). In vitro, FANCJ overexpression was correlated with 5-FU resistance in MLH1-proficient HCT116 3-6 cells, but not in MLH1-deficient HCT116 cells. Conclusions: FANCJ could be a useful biomarker to predict the response to 5-FU and prognosis of CRC, particularly in tumors with normal MLH1 expression.
Tumor burden (TB) as a prognostic indicator in patients with metastatic colorectal cancer (mCRC).
Authors: Kiley Wei Jen Loh, Jeremy David Shapiro, Ben Tran, Hui-Li Wong, Shu Fen Wong, Gary Edward Richardson, Michael Harold, Peter Gibbs
Journal: Journal of Clinical Oncology (2014)

572 Background: At initial diagnosis of mCRC, accurate assessment of patient prognosis is critical to defining the optimal initial treatment strategy. While performance status (PS) and number of metastatic sites are presumed surrogates of TB, to date TB assessment has not been formally examined as a potential prognostic marker in mCRC, despite supportive evidence in other malignancies. Methods: We developed a CT-based scoring system for TB on mCRC patients from the TRACC (Treatment of Recurrent and Advanced Colon Cancer) database. Objective (size and number of metastases) and subjective (clinical judgment) scoring systems were used to separate patients into high, moderate, or low TB subsets. Subjective scoring was repeated by a blinded second assessor on a subset of cases. Clinicopathologic correlates with TB were then assessed, along with survival outcomes for each subset. Results: 151 patients were assessed, median age was 68 years and 51% were male. Using subjective scoring, 55 (36%), 33 (22%), and 63 (42%) were categorized to high, moderate, and low TB subsets. Concordance between assessors using subjective scoring for 30 selected cases was 80% (high), 60% (moderate), and 90% (low). Factors correlating with increasing TB (high vs. low) on objective scoring were PS (31 vs 5% ≥ 2, p = 0.0002), number of disease sites (57 vs 9% ≥2, p &lt; 0.0001) and for patients with mCRC at presentation, reduced likelihood of primary CRC resection. Median overall survival was superior in low compared to high TB subsets for subjective (not reached vs. 15.9mths, p &lt; 0.0001) and objective (not reached vs. 14.7mths, p &lt; 0.0001) scores. Survival difference for low vs high TB were maintained on objective scoring even when patients with resectable metastases were excluded (22.7 vs. 11.9mths, p = 0.0017). Conclusions: TB measured subjectively or objectively is associated with overall survival in mCRC, and is a potential novel prognostic marker. Multi-variate analyses will be performed, and an independent validation cohort is being examined. As TB inversely correlated with primary resection for patients with mCRC at presentation, including TB assessment in further analyses of the survival impact of primary CRC resection is one potential application of this measure.
The Impact of the Association of Vinblastine during Induction Chemotherapy and as Maintenance Treatment in Children and Adolescents with High-Risk Anaplastic Large Cell Lymphoma: Results of a Randomized Trial of the EICNHL Group
Authors: Marie Cecile Le Deley, Angelo Rosolen, Alfred Reiter, Denise Williams, Keizo Horibe, Grazyna Wrobel, Georg Mann, Jozsef Zsiros, Anne Uyttebroeck, Ildiko Marky, Wolfgang Klapper, Laurence Brugieres
Journal: Blood (2008)
Financial and psychosocial impacts of adjuvant chemotherapy in older colorectal cancer patients.
Authors: E. B. Elkin, A. A. Hamilton, S. Patel, L. K. Temple, A. Stevenson, E. S. Weiss
Journal: Journal of Clinical Oncology (2010)

e19580 Background: Colorectal cancer often requires expensive, long-term treatment. Among the elderly in particular, CRC treatment may contribute to financial and psychosocial stress. Methods: We recruited patients age 65 or older receiving adjuvant chemotherapy for stage II or III CRC at Memorial Sloan-Kettering Cancer Center, its community-based regional sites or an affiliated minority-serving institution. In structured interviews we asked patients about cancer- and treatment-related worries and changes in paid and unpaid activities, as well as monthly pre-tax income, educational attainment and other sociodemographic characteristics. Results: Of 54 eligible patients seen in 2009, 45 enrolled in the study (response rate 83%). Mean age was 73 years, 84% had stage III CRC, 58% were male, and 47% were married. Seventy-four percent identified their race as white, 16% were black, and 10% were Asian, Hispanic/Latino or multiracial. One-third of patients reported a monthly income of $2,000 or less, and 13% did not complete high school. Patients with $2,000 or less in monthly income were more likely to report worry about disrupting holidays or special occasions, having to ask friends for help, families having to rearrange their lives around them, and being a burden to their families, compared with their higher-income peers. Patients in the lower income group were also more likely to report that someone in their household had to change the hours they work, work fewer hours, or quit their job since the patient's cancer diagnosis. Patients with more than $2,000 in monthly income were more likely to worry about being an emotional burden to a spouse or partner and more likely to have reduced or given up volunteer work or other regular activities as a result of their cancer diagnosis. Conclusions: Lower income elderly receiving adjuvant chemotherapy for stage II or III CRC were more likely than their higher income peers to worry about the impact of their cancer and treatment on family and friends, and to report an impact on the employment of a household member. Increased awareness and utilization of community-based resources may lower the risk of psychosocial and financial hardship associated with CRC and adjuvant treatment in older patients. No significant financial relationships to disclose.
A phase II study combining ipilimumab and fotemustine in patients with metastatic melanoma: The NIBIT-M1 trial.
Authors: A. M. Di Giacomo, P. A. Ascierto, E. Fonsatti, E. Pittiglio, P. Queirolo, L. Pilla, R. Ridolfi, M. Santinami, A. Testori, G. Parmiani, M. Maio
Journal: Journal of Clinical Oncology (2011)

TPS230 Background: CTLA-4 blockade by monoclonal antibodies (mAb) up-regulates host’s immune response(s) through the inhibition of negative signals delivered to T lymphocytes by the engagement with its counter-receptor B7. The anti-CTLA-4 mAb ipilimumab prolongs survival in pre-treated metastatic melanoma (MM) patients (pts). Though MM pts with brain metastases have been excluded from phase II-III trials with ipilimumab, initial evidences suggest that it might be effective as single-agent also in this clinical setting. Fotemustine, a cytotoxic alkylating drug that efficiently crosses the blood-brain barrier, is active as single-agent in MM. The Italian Network for Tumor Biotherapy (NIBIT) designed this study to investigate the clinical and immunologic efficacy of the combination of ipilimumab and fotemustine in MM pts with or w/o brain metastases. The rationale being that chemotherapy-induced spreading of tumor antigens might amplify the anti-tumor activity of ipilimumab. Correlative studies will also investigate the immunologic effects of the combination. Methods: The NIBIT-M1 is a phase II, open-label, single arm study that enrols unresectable stage III or IV cutaneous melanoma pts in seven NIBIT centres. Eligible pts with ECOG performance status of 0 or 1, may have received one prior systemic treatment and present asymptomatic brain metastases. Ipilimumab is administered i.v. at 10 mg/kg q3 weeks (wk) for 4 doses and once q12 wk from wk 24; fotemustine is administered i.v. at 100 mg/m2 weekly for 3 wk, and q3 wk from wk 9. Primary objective is to assess the immune-response (ir) Disease Control Rate using the immune-related response criteria. Among secondary objectives are to assess: safety, tolerability and feasibility of treatment; irObjective Response Rate, irDuration of Response, irProgression Free Survival (PFS), Brain-PFS, 1 and 2 years Survival Rates, and Overall Survival. Extensive laboratory studies will correlate the humoral and cellular immuno-modulatory activity of the combination with clinical outcomes. A pre-specified safety analysis at 18 pts enrolled was successfully met and accrual resumed on January 2011; to date, 28 of 84 planned pts have been enrolled.
Neoadjuvant carboplatin in stage IIa and IIb seminoma.
Authors: Alan Horwich, David Paul Dearnaley, Aslam Sohaib, Kjell Pennert, Robert Anthony Huddart
Journal: Journal of Clinical Oncology (2013)

321 Background: Approaches to managing stages IIa and IIb seminoma post-orchidectomy range from combination chemotherapy (typically 3 cycles of BEP) to extended field radiotherapy (typically 36 Gy to para-aortic and ipsilateral pelvic lymph nodes. Survival rates are very good, which highlights the need to minimise toxicity risks. We report on the role of a single cycle of neoadjuvant carboplatin prior to limited field radiotherapy. Methods: In a single arm study fifty one patients were treated between May 1996 and November 2011 with a single cycle of carboplatin at an AUC of 7 mg.mins/ml followed by radiotherapy. The radiation field was reduced to just the para-aortic region and the dose to 30Gy in 39 patients. Results: After a median follow-up of 55 months (range 8-151 months) with 38 (74%) of the patients having been followed for more than 2 years, there have to date been no relapses (95% confidence limits of 5 year relapse free survival of 93-100%). Toxicity has been low with grade 3 toxicity limited to 4 patients with grade 3 haematological toxicity (with no clinical sequelae) and 1 patient with grade 3 nausea (during radiotherapy). No patients experienced grade 4 toxicity. Conclusions: The results of this pilot study suggest that a single cycle of neoadjuvant carboplatin prior to radiotherapy may reduce recurrence risk and permit a smaller radiation field, and this approach is proposed for further investigation.
Junior doctor reinstated after suspension for fabricating research data
Authors: Clare Dyer
Journal: BMJ (2017)

A junior doctor who narrowly avoided being struck off the UK medical register after fabricating research data and citing senior colleagues as co-authors without their knowledge has been allowed to resume practice after a 12 month suspension.

Gemina Doolub, 31, was told by a medical practitioners tribunal last year that her fate had been finely balanced between erasure and the maximum suspension of 12 months. The tribunal chose the less severe option because they believed that she was unlikely to repeat the offence.1

Doolub, who qualified …
Salvage therapy with bicalutamide 80mg in patients with PSA failure under medical or surgical castration for prostate cancer
Authors: Y. Fujii, S. Kawakami, T. Kobayashi, H. Masuda, F. Koga, K. Saito, Y. Sakai, Y. Kageyama, K. Kihara
Journal: Journal of Clinical Oncology (2008)

16010 Background: Previous American studies reported modest effects of deferred use of bicalutamide 150mg in patients with hormone refractory prostate cancer (HRPC) during androgen deprivation monotherapy (ADMT). The objective of the current study was to evaluate the potential benefit of sequential introduction of bicalutamide 80mg therapy in Japanese patients with rising PSA under definitive LHRH agonist therapy or surgical castration for prostate cancer. Methods: Forty-seven patients with HRPC during ADMT were treated with deferred combined androgen blockade (CAB) therapy, administering bicalutamide 80mg once-daily. HRPC was defined biochemically as three consecutive rises in PSA levels during ADMT. The treatment response was defined as a 50% or greater decline in PSA levels. Prognostic values of various pretreatment parameters for responsiveness to deferred CAB were statistically determined. When the disease relapsed during deferred CAB, bicalutamide was discontinued and the patients were evaluated for the antiandrogen withdrawal syndrome (AWS). Results: Of the 47 patients, 31 (66%) experienced a PSA response. The median PSA failure-free survival was 10 months. Biopsy Gleason score (GS) was the only pretreatment variable predictive of a PSA response (mean GS 7.9 in responders and 8.8 in non-responders, P=0.017). Biopsy GS (6 or 7 vs. 8–10: HR 1.51, P=0.028) and PSA-doubling time (PSA-DT less than 4 vs. 4 or more: HR 0.67, P=0.018) were the only statistically significant variables of PSA failure-free survival in multivariate analysis. None of the variables including serum PSA levels, response or duration of response of first line ADMT or presence or absence of metastatic lesions were not related to the response of deferred CAB or PSA failure-free survival. Responders to deferred CAB had statistically longer cancer-specific survival than non- responders. None of 22 patients who were evaluated for AWS had the condition. Conclusions: Deferred CAB using bicalutamide 80mg is effective second line therapy at least in Japanese patients with progression during ADMT, particularly in those with lower GS tumors or longer PSA-DT. AWS after deferred CAB is uncommon. No significant financial relationships to disclose.
Response-based outcomes in patients with esophageal cancer treated with primarily non-cisplatin and 5-fluorouracil–based trimodality therapy.
Authors: N. K. Malik, G. W. Warren, G. Yang, K. Zeeck, T. Papsidero, S. Patil, N. I. Khushalani, T. Sher, S. S. Yendamuri, H. R. Nava, K. Salerno May
Journal: Journal of Clinical Oncology (2011)

e14620 Background: Response based outcomes in esophageal cancer patients treated with primarily non cisplatin and 5-fluorouracil based trimodality therapy Methods: Beginning in 2002 at Roswell Park Cancer Institute, alternative neoadjuvant concurrent chemoradiotherapy regimens using combinations of cisplatin, oxaliplatin, irinotecan, or capecitabine were used in the treatment of esophageal cancer patients receiving trimodality therapy. Patients who completed neoadjuvant treatment followed by surgical resection between October 2002 and April 2010 were analyzed. Survival was compared between patients with pathologic complete response (pCR) and those with pathologic non-complete response (pNCR). Follow up was calculated from the date of diagnosis to the date of death or last follow up. Unknown disease status was categorized as a recurrence. Unpaired t-tests were used for statistical comparisons. Results: A total of 115 patients were analyzed, of whom 93% of patients received non cis-5FU based neoadjuvant chemotherapy (40% with cisplatin-irinotecan based therapy, 32% oxaliplatin-capecitabine based regimens, and 15% oxaliplatin-5 FU based chemotherapy). pCR was noted in 19.1% of patients. There was no difference in gender, histology, proportion of patients receiving non cis-5FU based chemotherapy, mean radiotherapy dose delivered, chemoradiotherapy completion time, or total follow up time between patients with pCR and pNCR. With an overall median follow-up time of 28 months, survival analysis demonstrated that pCR patients had decreased disease recurrence (23% vs. 49%, p=0.0232), improved disease specific mortality (9% vs. 46%, p=0.001), and increased overall survival (77% vs. 44%, p=0.0048). Conclusions: In esophageal carcinoma patients treated with primarily non cis-5FU based neoadjuvant concurrent chemoradiotherapy followed by surgical resection, pathologic complete response appears to predict a significantly decreased risk of disease recurrence and improved survival.