tbuckley/cabot-search huggingface dataset:
Significance of MYC rearrangement and chemotherapy type on survival outcomes of patients with central nervous system lymphoma.
Authors: Natalie Sophia Grover, Allison Mary Deal, Stephanie Mathews, Ashley Freeman, Christopher Dittus, Steven I. Park
Journal: Journal of Clinical Oncology (2017)

7548 Background: Central nervous system lymphoma (CNSL) has a poor prognosis and an optimal treatment regimen has not been established. Due to the rarity of this disease and frequently poor performance status at diagnosis, there have been few prospective therapeutic clinical trials in this patient population. We therefore performed a retrospective analysis of prognostic factors and treatment outcomes of patients with CNSL treated at a single institution. Methods: Pathology records were used to identify patients diagnosed with CNSL from 1/1/2005 to 9/1/2016 at the University of North Carolina Cancer Hospital. Information about demographics, disease characteristics, treatment, and outcomes was gathered from the electronic medical record. Overall (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Results: We identified 100 patients with CNSL. 49% had primary CNSL (PCNSL). 78% of cases were diffuse large B cell lymphoma. Out of 51 patients evaluated for MYC translocation by FISH, 13 were positive (3 PCNSL and 10 secondary CNSL). Out of 74 patients treated with chemotherapy, 51% received methotrexate (MTX), procarbazine, and vincristine (MPV), with or without rituximab, 28% were treated with other high dose MTX based regimens, with or without rituximab, and 20% received a non-MTX based regimen. There was no significant difference in OS between PCNSL and secondary CNSL (13.7 vs 7.9 months, p = 0.97). Patients with MYC translocation had a worse OS compared to those without MYC translocation (5.1 vs 29.5 months, p = 0.004). Patients treated with MPV had a longer PFS compared to those treated with other high dose MTX based regimens or those who were treated with a non-MTX based regimen (19.1 vs 10.9 vs 3.9 months, p = 0.05), but difference in OS did not reach statistical significance (29.5 vs 22.4 vs 10.6 months, p = 0.12). Conclusions: In this single institution analysis of CNSL, MYC translocation was associated with worse survival. MPV was associated with improved PFS compared to other chemotherapy regimens. Further prospective studies are needed comparing MPV to other MTX-based regimens in CNSL.
HER2 activity in solid tumors.
Authors: Lara Ann Kujtan, Scott Morris, Janakiraman Subramanian
Journal: Journal of Clinical Oncology (2017)

e23121 Background: ERBB2 is a member of the human epidermal growth factor receptor family. HER2 expression that is immunohistochemistry (IHC) 3+ or IHC 2+ with copy number gain is an effective predictor for treatment with trastuzumab in breast and gastroesophageal cancers. Here we present an analysis on HER2 activity measured by IHC, mRNA expression and copy number variation (CNV) across a variety of solid tumors. Methods: The study population consists of patients diagnosed with solid tumors (n = 856) that underwent a Paradigm Diagnostic Cancer Test during 2016. We then analyzed tumor types that tested positive for HER2 by IHC (3+), CNV and/or mRNA expression. Results: We identified 365 (43%) patients positive for HER2 by IHC, 258 (30%) had high HER2mRNA expression and 41 (5%) had amplification by CNV. Seventy-five patients were HER2 IHC 3+ or 2+/CNV positive. The proportion of HER2 IHC 3+ or 2+/CNV positive tumors in each tumor type was as follows: breast cancer 41 (18.5%), NSCLC 10 (8.1%), colorectal 6 (6.7%), esophago-gastric 3 (10%,) urothelial/bladder 3 (16%), biliary 2 (28.6%), ovarian cancer 2 (5.1%) and pancreas 1 (3.1%). Using copy number gain as the gold standard, across all tumor types, an IHC of 3+ had a 90.2% sensitivity and a 95.6% specificity. In the same analysis with breast cancers omitted, the sensitivity was 75%, and specificity 96.8%. Whereas high mRNA expression had a sensitivity of 97.6% and specificity of 73.3%, omitting breast cancers, the sensitivity was 93.8% and specificity 73.2%. Conclusions: HER2 activity was identified in a wide variety of solid tumors and a small but significant proportion of these tumors maybe candidates for treatment with HER2 inhibitors such as trastuzumab. Our analysis also identified that HER2 activity in breast cancers has a distinctive pattern which was not seen in other tumor types. HER2 IHC 3+ expression was much less sensitive among other tumor types compared to breast cancer. mRNA expression, while remaining sensitive among other tumor types, is not specific, even among breast cancer patients. Our analysis also identified that HER2 activity in breast cancers has a distinctive pattern which was not seen in other tumor types.
Predictions, Surprises, and the Future of the Dermatology Workforce
Authors: Martina L. Porter, Alexa B. Kimball
Journal: JAMA Dermatology (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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
Clinical utilization of the Myeloid Malignancies Mutation Panel.
Authors: Saad A Arain, Aric C. Hall, Ryan J. Mattison
Journal: Journal of Clinical Oncology (2017)

e18523 Background: The scientific community has made tremendous progress in discovering genetic changes that drive myeloid malignancies and elucidating the effect of these mutations on prognosis. Still, the links between mutational profiling and management decisions remain unclear. In an effort to determine its clinical utility, we evaluated the use of the Myeloid Malignancies Mutation Panel (MMMP) at our institution. Methods: The MMMP is an assay of 57 genes with possible diagnostic, prognostic, or therapeutic implications for myeloid malignancies run by ARUP Laboratories. The assay was run on 30 patients at the University of Wisconsin – Madison between 6/2015 and 8/2016: 18 with leukemia, 5 with myelodysplastic syndrome, and 7 with “other” diagnoses (unexplained cytopenias, myeloproliferative disorders, or myelodysplastic/myeloproliferative overlap syndromes). Separate questionnaires for hematologists and hematopathologists were created asking 1) if the results of the MMMP were expected and 2) if the results changed diagnosis or management for each patient. Results were coded in a binary “yes/no” system and further subdivided by disease risk and category of response. Results: Hematologists considered the MMMP results expected for 8 patients and unexpected for 22. Per hematologist assessment, test results affected management (changed risk assessment, monitoring parameters, or drug therapy) for 14 of the 30 patients. Per the hematopathologists, the MMMP results were expected for 17 patients and unexpected for 13. For 11 patients, the diagnosis was affected (confirmed a suspected diagnosis or reassured against malignancy), while for 19 patients, the diagnosis was unchanged. Notably, in half of this group for whom diagnosis was unchanged, the hematopathologists believed there were significant prognostic implications. Conclusions: This data suggests the MMMP had significant implications in the diagnosis and management of myeloid disorders for nearly half of our patients. Clarifying this utility further to determine optimal cost-effective application of this expensive testing will require additional evaluation.
A retrospective comparison of taxane and fluorouracil-based chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma.
Authors: Shuiyun Han, Feiying Gu, Gang Lin, Chenxue Jiang, Xiaojiang Sun, Zhun Wang, Yuezhen Wang, Yaping Xu, Weimin Mao
Journal: Journal of Clinical Oncology (2016)

e15561 Background: To retrospectively compare taxane-based with fluorouracil-based chemoradiotherapy in terms of toxicity profiles, efficacy and survival in patients with inoperable esophageal cancer. Methods: We analyzed retrospectively 179 consecutive patients who were unresectable or medically unfit for surgery between March 2009 and November 2014. Eight-three patients were included in the taxane group and 96 cases were in the fluorouracil group. Results: The overall response rate (ORR) in the taxane group was higher than fluorouracil group, but was not significantly different (71.6% vs. 63.5%, respectively, P=0.255). In total, 53.0% (44/83) of the patients in the taxane group had progressive disease versus 54.2% (52/96) in the fluorouracil group (not significantly different (P=0.758)). There were no significant differences in overall response rate or in median progression free survival and overall survival, as well as treatment-related death. In terms of non-hematological toxicity, patients in the taxane group experienced a lower incidence of ≥ grade 3 esophageal perforation or fistula (4.8% vs. 13.5%, P=0.047) and pneumonia (4.8% vs. 9.7%, P=0.242). Regarding hematological toxicity, thrombocytopenia in the taxane group was significantly lower (4.8% vs. 13.5%, P=0.047), but there was a trend towards a higher rate of ≥ grade 3 leukopenia (34.9% vs.26.0%, P=0.196). Conclusions: Chemoradiation with taxane-based regimens is well tolerated, with potentially promising efficacy, and could become a good alternative treatment in a first line setting for patients with inoperable esophageal squamous cell carcinoma. Event( (≥ grade 3)) Taxane group (n=83) Fluorouraci group (n=96) P value Hematological toxicity 35(42.2) 42 (43.8) 0.831 Leukopenia 29 (34.9) 25 (26.0) 0.196 Anemia 4 (4.8) 8 (8.3) 0.349 Thrombocytopenia 4 (4.8) 13 (13.5) 0.047 Non-hematological toxicity Mucositis 16 (19.3) 22 (22.9) 0.553 Esophageal perforation 4 (4.8) 13 (13.5) 0.047 Pneumonia 4 (4.8) 9 (9.7) 0.242 Treatment-related death 1 (1.2) 3 (3.1) 0.625
Homologous recombination deficiency and platinum rechallenge in platinum-resistant ovarian cancer patients.
Authors: Alexandre Andre B. A. Da Costa, Marcela Marinelli Salvadori, Camila Vieira Valadares, Carlos Stecca, Louise Brot, Luisa Matos do Canto, Glauco Baiocchi, Silvia Regina Rogatto, Maria Isabel Waddington Achatz
Journal: Journal of Clinical Oncology (2017)

5576 Background: Ovarian carcinomas show homologous recombination deficiency (HRD) in up to 50% of cases and in 15 to 20% of cases occur due to germline BRCA1 or BRCA2 mutations. BRCA mutated tumors are more sensitive to PARP inhibitors and platinum based chemotherapy. The objective of this study was to characterize a cohort of ovarian cancer patients regarding HRD and to evaluate the impact of these scores in prolonged platinum sensitivity. Methods: Thirty one ovarian cancer patients with platinum resistant recurrence reexposed to platinum based chemotherapy were selected. Paraffin embedded tumor samples from 14 patients were analyzed using ONCOSCAN assay (Affymetrix) to evaluate HRD scores. The association of the scores with response rate to platinum rechallenge, overall survival and clinical pathologic factors was evaluated. Results: From the cohort of 31 patients, 15 samples from 14 patients were analyzed for genomic alterations. Median scores were 19.5 for TAI, 12.5 for cnLOH+L, 26.0 for LST and 6.3 for HRD. High scores were found in 10 out of 14 (for cnLOH+L score) and 9 out of 14 (for LST score) patients. Seven of the 14 patients analyzed analyzed for genomic alterations had response, which suggested homologous recombination deficiency. No significant differences were observed between response rates for high versus low scores. Numerically, cnLOH+L, LST and HDR scores were higher in patients with response to treatment compared to those without response. Median overall survival was 13.4 months from the beginning of platinum rechallenge and no difference in survival according to scores was observed. Among the clinical pathologic factors, family history of breast or ovarian cancer or personal history of breast cancer was associated to higher response rate to platinum rechallenge. Conclusions: In conclusion,HRD scores showed to be potential markers of response to platinum rechallenge in the platinum resistant setting. Further studies are necessary to clarify the best cutoffs for each score, the impact of tumor heterogeneity and the analysis of tumor samples in the moment of treatment. Positive family history of cancer is a clinical factor predictvie of platinum rechallenge response.
Cervical cancer survival in Ghana.
Authors: Yvonne Nartey, Brian Cox, Philip Hill, Kwabena Amo-Antwi
Journal: Journal of Clinical Oncology (2016)

e17007 Background: Despite the fact that cervical cancer is potentially preventable through HPV vaccination and screening, an estimated 266,000 women died of the disease in 2012. Cervical cancer ranks as the most frequent cancer among women in Ghana. There have been no data regarding cervical cancer survival in Ghana. Cancer survival is an important indicator of the performance of the health system. Methods: Information on invasive cervical cancer cases diagnosed between 2010 to 2013 was collected from Komfo Anokye and Korle Bu Teaching Hospitals through review of medical, pathology and computer records at the oncology unit and the departments of obstetrics and gynaecology. Telephone interviews were also conducted with patients and relatives to gather further data. Data were recorded using a standardised study data collection sheet and analysed using summary statistics. Using the multivariate proportional hazards model, survival and hazard rates were calculated. Adjustment was made for age at diagnosis, stage at presentation, histological type, comorbidity and treatment. Results: Information for 821 women were available for the survival analysis. Of these women, 497 (60.5%) died during follow-up. The years of follow-up available varied from one to five years depending on when patients were diagnosed in the 2010-2013 period. At three years from diagnosis, overall survival was 39%. Five years after diagnosis, survival was 30%. In the multivariate model, compared to women with FIGO stage I disease, survival was two times lower in those with stage II (HR: 2.35; 95% CI: 1.26-4.39; p = 0.007) and seven times lower in those with stage IV disease (HR: 7.77; 95% CI: 4.07-14.82; p < 0.001) after adjustment for age at diagnosis, stage, histological type, grade of differentiation and treatment. Receiving no treatment was a very strong predictor of poor survival in both the univariate (HR: 18.06; 95% CI: 4.48-72.78; p < 0.001) and multivariate models (HR: 15.73; 95% CI: 3.82-64.71; p < 0.001). Conclusions: The results show that early diagnosis and treatment are essential for reducing mortality and increasing survival from cervical cancer in Ghana. The low cervical cancer survival emphasizes the need for urgent investment in improving awareness and early detection programs in Ghana.
Prospective phase II study of sunitinib rechallenge in metastatic renal cell carcinoma (mRCC): A G.I.O.N. trial.
Authors: Camillo Porta, Vittorio D. Ferrari, Paolo Andrea Zucali, Giuseppe Fornarini, Antonio Bernardo, Andrea Falconeri, Alessandra Ferrari, Sandra Santarossa, Giovanni L. Pappagallo, Alessandra Bearz
Journal: Journal of Clinical Oncology (2017)

e16081 Background: Sunitinib is a 1 st -line standard of care in mRCC. Lack of cross-resistance to sequential VEGF-targeting drugs and the possibility of a successful rechallenge with Sunitinib have been postulated. Whether mRCC patients (pts) could benefit from rechallenge with Sunitinib after progressing on 1 st -line Sunitinib and 2 nd -line Everolimus was the aim of this phase II study Methods: 39 mRCCpts were prospectively treated with Sunitinib (50 mg/daily, 4:2); main inclusion criteria were: histologically proven RCC with clear cell component, previous 1 st -line Sunitinib with a Disease Control Rate lasting at least 10 months, 2 nd -line Everolimus, and written informed consent. The primary end-point of this study was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing Sunitinib on 12 pts in the first stage, the trial would have been terminated if 5 or fewer had a PFS of less than 6 months. Otherwise, the trial would have proceeded to the second stage, enrolling a total of 38 pts. If the total number of pts free of progression at 6 months would have been less than or equal to 18, Sunitinib would have been rejected Results: As a whole, 39 pts (30 males, 9 females) were enrolled. The study quickly moved from the first stage to its completion and ultimately succeeded; indeed, 6-months PFS was 60%, median PFS being 8.6 months (average: 9.59, range: 0.7-24.6 months). In terms of safety no unexpected toxicities were observed. Tx-related grade 3-4 AEs observed in ≥5% of the pts were: hand-foot skin reaction, fatigue, nausea, hypertriglyceridemia, hypophosphatemia, hypocalcemia, hyperglycemia, and neutropenia. One case each of myocardial infarction, atrial flutter and spontaneous pneumothorax were also reported, but resolved Conclusions: Despite an ineluctable time-lead-bias, median PFS on Sunitinib rechallenge was high (8.6 months), clearly showing that many pts may become sensitive again to VEGFRs-inhibition. Although many agents are presently available from 2 nd -line on, in countries where treatment options are still limited, Sunitinib rechallenge could still represent a reasonable treatment option. EudraCT number: 2012-000473-23. Clinical trial information: 2012-000473-23.
Outcomes among minority patients with stage IV colorectal cancer in the Harris County Health System.
Authors: Kelsey S. Lau-Min, Preeti Prakash, Aaron Thrift, Benjamin Leon Musher
Journal: Journal of Clinical Oncology (2017)

e18039 Background: Colorectal cancer (CRC) mortality has declined over the last three decades, but significant racial disparities in CRC survival continue to be reported, especially for stage IV disease. Hypothesizing that these disparities arise from differences in access to care rather than tumor biology, we examined treatment patterns and outcomes among minority patients evaluated and treated for stage IV CRC in an academic safety net health system. Methods: The Harris Health System is an integrated health delivery network that utilizes tax revenue to care for predominantly minority and uninsured residents of Harris County, Texas. As the largest Harris Health facility and an affiliate of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine, Ben Taub Hospital delivers cancer care through multidisciplinary subspecialty clinics and a robust patient assistance program. We performed a retrospective analysis of minority patients diagnosed with stage IV CRC between 1/2010 and 12/2012 who were evaluated and treated at Ben Taub Hospital. Results: We identified 103 patients of whom 40% were black, 49% were Hispanic, and 12% were Asian or Middle Eastern. 65% spoke English as their preferred language; 74% were uninsured and covered by the Harris Health Plan, a financial assistance program for individuals with incomes under 300% of the federal poverty level. 85% of patients received cancer-directed therapy, of whom 99% received standard chemotherapy with a best response rate of 67% and a disease control rate of 87%. Median overall survival was 20.7 months for all patients and 23.0 months for patients who received chemotherapy. Conclusions: The Harris Health System provides the health delivery infrastructure through which minority patients with significant socioeconomic challenges obtain financial assistance and access to quality cancer care in an academic setting, thereby leading to clinical outcomes comparable to those of the predominantly Caucasian and insured populations studied in randomized control trials. Efforts to resolve disparities in CRC outcomes should focus on improving access of at-risk populations to comprehensive cancer care.
An intergroup phase III trial of ramucirumab plus irinotecan in third or more line beyond progression after ramucirumab for advanced gastric cancer (RINDBeRG trial).
Authors: Daisuke Sakai, Narikazu Boku, Yasuhiro Kodera, Yoshito Komatsu, Masashi Fujii, Satoru Iwasa, Eiji Oki, Wasaburo Koizumi, Makio Gamoh, Kei Muro, Toshio Shimokawa, Taroh Satoh
Journal: Journal of Clinical Oncology (2018)

TPS4138 Background: Ramucirumab, an anti-VEGFR2 fully human monoclonal IgG1 antibody showed survival benefits in two randomized trials of 2nd line chemotherapy for advanced gastric cancer (AGC), and ramucirumab plus paclitaxel is recognized as 2nd line standard treatment. It has been suggested that sustained VEGF blockade might contribute to long-term disease control in various cancers. Methods: This randomized phase III study comparing irinotecan ± ramucirumab recruits patients with AGC from 110 institutions participating in 9 clinical trial groups in Japan. Primary endpoint is overall survival (OS), with the assumed hazard ratio of 0.77 (power of 80% and significance level of one-sided 0.05). Secondary endpoints include progression-free survival, time to treatment failure, response rate, disease control rate, and safety. Major eligibility criteria are: 1) histologically proven gastric or esophagogastric adenocarcinoma, 2) unresectable or recurrent disease, 3) two or more lines of chemotherapy with platinum, fluoropyrimidines, taxanes, and ramucirumab (no prior use of irinotecan), 4) disease progression during prior chemotherapy containing ramucirumab, 5) age ≥ 20years, 6) performance status (PS) 0-1, 7) evaluable disease as defined in the RECIST v1.1, 8) adequate hematologic, renal, hepatic and metabolic function (including urinary protein = 0 or 1+), 9) expected survival ≥ 90 days, 10) written informed consent. Patients are randomly allocated (1:1) to ramucirumab plus irinotecan or irinotecan alone. Irinotecan is administered at a dose of 150 mg/m2, every two weeks, in both arms, and ramucirumab at a dose of 8 mg/kg is added biweekly. Status: Opened to accrual February 2017, at 31 Jan 2018, 87/400 patients have been enrolled. Clinical trial information: UMIN000023065.