tbuckley/cabot-search huggingface dataset:
Immune checkpoint inhibitor (ICI) treatment in advanced melanoma (aMel) patients (pts) with renal or hepatic dysfunction (dysf): Real-world patient characteristics and outcomes.
Authors: Susan Spillane, Amy Pickar Abernethy, Nicholas R Brown, Andrew N Freedman, David Lenis, Kathleen Maignan, Angela Mariotto, Rebecca A. Miksad, Aracelis Z. Torres, Elad Sharon
Journal: Journal of Clinical Oncology (2018)

9569 Background: ICIs were approved for first line (1L) therapy in aMel. However, pts with renal or hepatic dysf are often excluded from clinical trials; little is known about usage or outcomes for these pts. Methods: We retrospectively analyzed de-identified real-world data aggregated by Flatiron Health from US community oncology practices. Pts had confirmed aMel, a documented order/administration of an ICI as 1L therapy from 1/1/11 to 12/1/17 and ≥1 hepatic or renal lab value up to 30 days before 1L start. Renal [serum creatinine (cr)] and hepatic [total bilirubin (Tbili), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)] function labs were graded by Common Terminology Criteria for Adverse Events v4.03. Dysf was defined as grade 2+. Categorical variables were assessed using Chi-square test; continuous variables with Kruskal-Wallis test; therapy duration and OS with log-rank test. Results: 1475 pts with relevant data were identified (Table). Conclusions: In this real-world aMel cohort, <3% of ICI-treated pts had baseline hepatic or renal dysf. Relative to pts with normal organ function, pts with baseline renal dysf were more often male and were more likely to be older. Although only hepatic dysf was significantly associated with shorter ICI duration, both renal and hepatic dysf pts had significantly shorter median OS. The OS findings may reflect competing risk from underlying comorbidities, practice patterns, tolerance (renal dysf), toxicity and/or ICI efficacy in the setting of organ dysf. Additional research is needed to better understand ICI treatment for real-world pts with baseline renal or hepatic dysf. Baseline Renal Hepatic Normal N=1396 Dysf N=37 (2.6%) p-value Normal N=1272 Dysf N=31 (2.4%) p-value Demographics Male, % 67.5 87.0 .023 68.5 67.7 .999 Age, median years (IQR) 68 (58.0, 77.0) 78 (73.0, 81.0) <.001 68 (58.0, 77.0) 64 (62.5, 75.0) .940 ICI duration Median, days (IQR) 68 (43, 238) 64 (43, 107) .178 69 (44, 231) 22 (1, 64) <.001 OS Median, months (IQR) 20.8 (6.2, *) 7.9 (2.6, 18.2) <.001 19.9 (6.0, *) 2.7 (1.1, *) <.001 Normal = Grade 0-1; dysf = Grade 2-3, * = not observed
Association of CEP72 genotype with chemotherapy-induced neuropathy.
Authors: Vaibhav Agrawal, Diane T. Smelser, David J. Carey, Sharif S. Khan, Joseph Vadakara
Journal: Journal of Clinical Oncology (2016)

e14107Background: Chemotherapy-induced neuropathy (CIN) frequently results in dose reduction or therapy discontinuation. An associated risk of vincristine-related neuropathy has been previously rep...
Million Hearts 2022
Authors: Janet S. Wright, Hilary K. Wall, Matthew D. Ritchey
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
TIGER-3: A phase 3 multinational open-label randomized study of rociletinib vs investigator-choice chemotherapy in patients (pts) with epidermal growth factor receptor mutant-positive (EGFRm) non-small cell lung cancer (NSCLC) progressing on prior EGFR tyrosine kinase inhibitor (TKI) therapy and doublet chemotherapy.
Authors: James Chih-Hsin Yang, Sanjay Popat, Silvia Novello, Harry J.M. Groen, Maurice Perol, Enriqueta Felip, Frank Griesinger, Karen L. Reckamp, Jong-Seok Lee, Egbert F. Smit, Collin M. Blakely, Wallace L. Akerley, Young-Chul Kim, Lyudmila Bazhenova, Raffaele Califano, Richard Delmar Hall, Panayiotis Georgiou, Jeffrey D. Isaacson, Tony Golsorkhi, Heather A. Wakelee
Journal: Journal of Clinical Oncology (2016)

TPS9106 Background: Rociletinib is a small molecule TKI that selectively targets EGFRm, and in preclinical studies inhibited L858R, del19, and T790M while sparing wild-type EGFR. In TIGER-X (NCT01526928), a phase 1/2 dose-finding trial, rociletinib had promising and durable antitumor activity in pts with NSCLC and positive T790M status following progression on a TKI (Sequist et al. N Engl J Med 2015;372:1700-9; Sequist et al. J Clin Oncol 2015;33(suppl):abstr 8001). TIGER-3 is investigating single-agent rociletinib vs chemotherapy in pts who have failed EGFR therapy and platinum-based doublet chemotherapy. TIGER-3 will evaluate pts with T790M-positive and -negative status based on blood and tumor tissues and biomarkers of response or resistance. Methods: Pts with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with radiological progression on the most recent therapy are being enrolled in a phase 3, multinational, randomized, open-label study (NCT02322281). Pts must have documented evidence of a tumor with ≥ 1 EGFR activating mutations, excluding exon 20 insertion, and prior treatment with an EGFR TKI and platinum-containing doublet chemotherapy. Pts are being randomized to receive rociletinib or single agent cytotoxic chemotherapy (investigator choice specified before randomization) until disease progression. Pts randomized to chemotherapy may cross over to receive rociletinib upon progression. Pts will be stratified by presence or absence of brain metastases, ECOG Performance Status (0 vs 1), and race (Asian vs non-Asian). The primary endpoint is progression-free survival. Secondary endpoints include objective response rate, duration of response, disease control rate, overall survival, and pt-reported outcomes. Serial assessment of safety will be carried out based on standard adverse event reporting. Planned enrollment is 900 pts; recruitment is underway in approximately 150 sites in Asia, Australia, Europe, and North America. Clinical trial information: NCT02322281.
Generational Differences in Mentoring Relationships
Authors: Haider Javed Warraich
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Impact of vascular endothelial growth factor (VEGF) and hypoxia-inductible factor-1 alpha (HIF-1) expression on the prognosis of locally advanced cervical carcinoma (LACC) treated with radiochemotherapy.
Authors: Julia Madani, Beatriz Eizaguirre, Vicente Alonso, Teresa Puertolas, Esther Millastre, Eduardo Polo Marques, Juan Lao Romera, Ana Herrero, Antonio Anton
Journal: Journal of Clinical Oncology (2017)

e17023 Background: Combination of radiotherapy plus platinum-based chemotherapy (RT-CT) is considered the standard treatment in LACC. The risk of recurrence after local treatment is around 50-70%. The role of angiogenesis in tumor progression has been shown in large series. The aim of this study was to determinate the impact of the expression of VEGF and HIF-1 on disease-free survival (DFS) and overall survival (OS) in patients with LACC receiving RT-CT. Methods: Expression of VEGF and HIF–1 was assessed by an immunohistochemistry (IHC) assay in 115 cases. Inmunostainning was considered negative (&lt; 10% of cells), slightly positive (&lt; 25%), moderate (26%-50%) and strongly positive (&gt; 50%). A univariate analysis was carried out for each variable using the log-rank test. Subsequently, a multivariate analysis was performed employing Cox’s proportional hazards model. Results: 115 patients (p) with LACC were included and received RT-CT between January/2003 and December/2012. IHC revealed absence of expression of VEGF in 12 (10,4%) cases, slightly positive in 34 (29,6%), moderate in 30 (26,1%) and strongly positive in 39 (33,9%). The expression of HIF-1 was negative in 63 (54,8%) cases and positive (weak or moderate) in 52 (45,2%). 76p (66,1%) showed a complete clinical response (CR), 26p (22,6%) partial response and 13p (11,3%) stable disease or progression. The median follow–up was 35 months (1-140). 56p (48,7%) relapsed. Univariate analysis indicate that ECOG &gt; 1, tumor size ≥ 4,5 cm, FIGO stage III-IVA, lymph nodes positive, non CR, CA125 post-treatment ≥ 35 U/mL, hemoglobin levels &lt;11 mg/dl (basal, nadir and post-treatment), strong expression VEGF and positive expression of HIF – 1 were all associated with a significant lower OS and DFS. In multivariate analysis strong expression of VEGF remained statistically significant, as tumor size, non CR and hemoglobin level post-treatment &lt; 11g/dL. Conclusions: IHC-assessed strong expression of VEGF was independent prognostic factor of shorter OS and DFS in patients with LACC treated with RT-CT. IHC determination of VEGF could be useful in clinical practice.
Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience in an Italian referral centre
Authors: E. Bargagli, C. Piccioli, E. Rosi, E. Torricelli, L. Turi, E. Piccioli, M. Pistolesi, K. Ferrari, L. Voltolini
Journal: Pulmonology (2018)

Idiopathic pulmonary fibrosis has a median survival time after diagnosis of 2–5 years. The main goal of treating IPF is to stabilize or reduce the rate of disease progression. Nintedanib and Pirfenidone have been a breakthrough in the management of IPF. Here we evaluated the effectiveness of Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last 12 months at Florence ILD Referral Centre. In the last 12 months, 82 IPF patients (66 male, mean age 78.3 ± 23.8 years) were diagnosed and started antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and functional details were analyzed retrospectively at time 0 and after 6 and 12 months of therapy. The median age of the patients treated with Nintedanib was higher than that of the Pirfenidone group (p < 0.0001). The most common symptoms at disease onset were exertional dyspnoea and dry cough with no differences between the two groups (p < 0.05). All IPF patients manifested bibasal crackles at the time of diagnosis. No significant differences in FVC, FEV1, TLC and DLCO were found at time 0 or after 6 months between patients treated with Pirfenidone and Nintedanib (p > 0.05). After 1 year, lung function test parameters of patients treated with Pirfenidone had remained stable from baseline. This study emphasizes that both antifibrotic drugs appeared to be a good therapeutic choice in terms of functional stabilization, also in older patients.
Quantification of BCR-ABL by digital PCR in samples with high copy numbers and rates of molecular responses (as defined by EUTOS) compared to those detected with standard quantitative real-time PCR.
Authors: Georg-Nikolaus Franke, Jacqueline Maier, Michael Cross, Kathrin Wildenberger, Francis J. Giles, Oliver Frank, Andreas Hochhaus, Christian Dietz, Martin C. Müller, Dietger Niederwieser, Thoralf Lange
Journal: Journal of Clinical Oncology (2016)

7056 Background: The Digital PCR (dPCR) technique has the potential to monitor minimal residual disease in patients with BCR-ABL positive leukemias, since it allows absolute quantification of the target sequence. A concern re dPCR is possible non-linearity at high copy numbers (CN). We assessed linearity for BCR-ABL and ABL quantitation by dPCR and compared the rates of molecular responses (MR), on the EUTOS scale, in patients (pts) with chronic myeloid leukemia (CML) who had received 18 months of nilotinib treatment in the ENEST1st trial (NCT01061177) as determined by dPCR or qPCR. Methods: 230 cDNA samples with e13 or e14/a2 BCR-ABL fusion genes were analysed in Leipzig (L, n = 75) or Mannheim (M, n = 155) by qPCR between 2012 and 2013. The cDNA samples were re-analysed in L by dPCR using a Droplet Digital PCR System (BIO-RAD). To assess the linearity of the assay, the ERM standard was diluted to BCR-ABL and ABL CN from 150000 to 1 and measured in replicate. Results by dPCR were about 20% lower than the calculated dilution. Linearity could be shown for CN as high as 120000 for ABL and BCR-ABL with a fraction of 81-165 negative droplets at the highest concentration. Results: The median CN of BCR-ABL and ABL was 12 (range 0-2050) and 59350 (range 7690-176000) by dPCR and 10 (range 0- 1529) and 53537 (range 4013 – 250800) by qPCR, respectively. Both methods detected similar numbers of BCR-ABL+ samples (dPCR 186, qPCR 189) with a median % BCR-ABL of 0.022 by dPCR compared to 0.019 by qPCR before, and 0.014 after, conversion to IS.he cumulative rates of MMR, MR4 and MR4.5 or better at 18 months of treatment were 83, 43 and 29% with qPCR. The distribution in MR classes was significantly different between the methods (p < 0.001), with dPCR indicating decreased cumulative rates of MR3, MR4 and ≥ MR4.5. Significantly fewer pts achieved ≥ MR4 when analyzed by dPCR (n = 77 vs. 100, p < 0.05). Of the 191 samples scored ≥ MMR by qPCR, 71 (37%) were one or more MR classes higher by dPCR. In contrast, only 13% were scored into a deeper MR class. Conclusions: dPCR is linear, even at high CN, and compared to qPCR, generates differing rates of MR in patients with CML .
ヒト浸潤性乳癌において,miR-125bはメチル化され,ETS1癌原遺伝子を制御することにより腫瘍抑制因子として機能する
Authors: Zhang Yan, Yan Li-Xu, WU Qi-Nian, DU Zi-Ming, Chen Jing, Liao Ding-Zhun, Huang Ma-Yan, Hou Jing-Hui, WU Qiu-Liang, Zeng Mu-Sheng, Huang Wen-Lin, Zeng Yi-Xin, Shao Jian-Yong
Journal: Cancer Research (2011)
Germinal Center B Cells Replace Their Antigen Receptors in Dark Zones and Fail Light Zone Entry when Immunoglobulin Gene Mutations are Damaging
Authors: Isabelle Stewart, Daniel Radtke, Bethan Phillips, Simon J. McGowan, Oliver Bannard
Journal: Immunity (2018)

Adaptive immunity involves the development of bespoke antibodies in germinal centers (GCs) through immunoglobulin somatic hypermutation (SHM) in GC dark zones (DZs) and clonal selection in light zones (LZs). Accurate selection requires that cells fully replace surface B cell receptors (BCRs) following SHM, but whether this happens before LZ entry is not clear. We found that most GC B cells degrade pre-SHM receptors before leaving the DZ, and that B cells acquiring crippling mutations during SHM rarely reached the LZ. Instead, apoptosis was triggered preferentially in late G1, a stage wherein cells with functional BCRs re-entered cell cycle or reduced surface expression of the chemokine receptor CXCR4 to enable LZ migration. Ectopic expression of the anti-apoptotic gene Bcl2 was not sufficient for cells with damaging mutations to reach the LZ, suggesting that BCR-dependent cues may actively facilitate the transition. Thus, BCR replacement and pre-screening in DZs prevents the accumulation of clones with non-functional receptors and facilitates selection in the LZ.
Interim metabolic tumor volume to predict response in diffuse large B-cell lymphoma.
Authors: Prioty Islam, Jordan Goldstein, Ila Sethi, Daniel Lee, Christopher Flowers
Journal: Journal of Clinical Oncology (2017)

7557 Background: DLBCL is a heterogeneous disease with varied clinical outcomes following treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). [ 18 F] fluorodeoxyglucose (FDG) – positron emission tomography (PET)/computed tomography (CT) imaging is ubiquitously used in monitoring of DLBCL. PET-derived metrics for analysis of tumor FDG uptake include: tumor maximum standardized uptake value (SUV); metabolically active tumor volume (MTV); and total lesion glycolysis (TLG), calculated from the intensity of FDG uptake in tumor volume. We evaluated the predictive value of interim SUV, MTV and TLG for patients (pts) with DLBCL treated with R-CHOP. Methods: Pts with DLBCL treated at Emory University 2005-2016 were eligible. Cases were included if there was a diagnosis of DLBCL confirmed by record review, available information on date of diagnosis, date of last contact or date of death. Analyses were restricted to patients who received R-CHOP and had PET/CT scans available at baseline, Cycle 2 or 4 and end of treatment. Maximum SUV, MTV, and TLG were calculated using MIM software for tumor with an SUV threshold of &gt; 4. Logistic regression analysis was used to calculate the predictive value of interim PET/CT metrics on end of treatment response. Results: Pre-treatment PET/CT scans for 42 patients were identified, along with 28 interim and 31 post-treatment scans. The mean pre-treatment MTV was 303ml (range 4 – 1,327) and mean TLG was 3188 (range 28 – 16,176). MTV and TLG were undetectable in 79% of interim scans and 74% of the post-treatment scans. A Deauville score of 3 or less was observed in 71% of the interim PET/CT scans and 56% of the post-treatment scans. A positive interim MTV was correlated with a positive post-treatment MTV and post-treatment Deauville score at 0.58 and 0.66, respectively, and a positive interim MTV result was a significant predictor of a positive post-treatment MTV result (p = 0.02). Conclusions: PET-derived metrics of assessing interim tumor response to therapy offer significant predictive value for end of treatment response, and can guide a response-adapted treatment approach for DLBCL pts that builds on the R-CHOP backbone.
Dietary patterns and attitudes in cancer patients.
Authors: Shu Fen Lee, David Wyld, Teresa Brown, Melissa A. Eastgate
Journal: Journal of Clinical Oncology (2018)

e22055 Background: There is evidence linking dietary factors to the risk of cancer but less is known on the effects of nutrition on prognosis after cancer diagnosis. Due to limited scientific knowledge in this area, nutritional guidelines for well nourished patients are based on general healthy eating recommendations. This study aims to describe patients’ beliefs and attitudes regarding diet and to explore the dietary information sought. Methods: We performed a single center prospective patient survey which was undertaken from July 2016 to January 2017. Patients being reviewed by the Medical Oncology Department at the Royal Brisbane Hospital were invited to complete an anonymous online questionnaire. Results: 109 patients completed the survey. 61% had curative treatment whilst 18% had palliative treatment. Median BMI was 26.9kg/m2. 72% reported a weight change, of which 39% lost weight. 62% modified their diet. Majority (69%) initiated the change themselves and most commonly was a reduction in overall food intake (40%). Very few followed a specific dietary plan. Majority (71%) did not feel that their diet caused their cancer but most (63%) felt that nutrition played an integral part in their treatment. Patients were more likely to modify their diet if they had experienced a weight change (OR 3.59, 95% CI 1.49-8.63), had malignancy related anorexia (OR 2.38, 95% CI 1.06-5.32), strongly believed that their diet contributed to their cancer (OR 9.09, 95% CI 2.55-32.44) or felt that nutrition played an important role in their treatment (OR 4.50, 95% CI 1.95-10.40). Patients most frequently sought dietary information from their hospital dietician (51%), the internet (39%) and their oncologist (35%). However, only 47% and 57% found the information provided by their hospital dietician and oncologist helpful, respectively. Conclusions: Our survey confirms that patients place great importance on diet as part of their cancer management but hospital clinicians are not necessarily providing dietary information to meet patient expectations. This identifies a potential gap in nutrition education between conventional dietary advice focused on protein and caloric intake to manage malnutrition, with that of complementary medicine practices focused on dietary therapy of cancer.
Circulating tumor DNA analysis before and after resection for colorectal cancer.
Authors: Erin L. Symonds, Susanne Kartin Pedersen, David Murray, Graeme P Young
Journal: Journal of Clinical Oncology (2017)

3597 Background: Detection of circulating tumor DNA (ctDNA) has broad clinical utility including disease monitoring, prognostication and response to chemotherapy. ctDNA is commonly detected by targeting tumor-specific features including mutations, insertions, deletions or hypermethylation. The two genes, BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC). This study aimed to analyze the impact of tumor resection on ctDNA levels by assaying pre- and postoperative blood samples for methylated BCAT1 and IKZF1. Methods: 91 people (age 32-86 years, 53% male) with invasive CRC, but without neoadjuvant therapy, had blood collected prior to surgery and within 12 months (1-12 months) after resection. Cancers were clinicopathologically staged. DNA extracted from plasma was assayed for methylated BCAT1/ IKZF1 and detection of either marker was deemed positive for ctDNA. Results: 47 (52%) of the 91 CRC patients were ctDNA positive before resection, including 5/30 (17%) stage I, 17/28 (61%) stage II, 23/31 (74%) stage III and 2/2 (100%) stage IV. After resection 75% (35/47) became ctDNA negative (median 2 months after resection), and all had apparent tumour clearance. Of the 35 postoperative ctDNA negative cases 22 had further surveillance CT scans within study timeframe. 86% (20/22) showed no recurrent CRC but 2 of these developed a new cancer (metachronous CRC, prostate). The remaining 2 tested ctDNA positive 14 and 25 months later and recurrence was confirmed. Of the 12 postoperative ctDNA positive cases, two were found to not have complete tumour clearance at surgery (residual disease). Follow-up CT scans were available for a further 8 patients which revealed that 4 later presented with cancer (3 recurrence, 1 thyroid) at a median 15 months after resection. The remaining 4 postoperative positive cases were negative at subsequent blood testing (median 8 months later). Conclusions: Methylated BCAT1/IKZF1 DNA in preoperative blood is dependent on tumor stage, but informs the completeness of resection given the high rate (74.5%) of ctDNA disappearance post-surgery. If cases persistently test ctDNA positive after surgery or become ctDNA positive later, residual or recurrent disease should be suspected, respectively.