tbuckley/cabot-search huggingface dataset:
Avelumab treatment for metastatic urothelial carcinoma in the phase Ib JAVELIN Solid Tumor Study: Updated safety and efficacy analysis with ≥ two years of follow-up.
Authors: Andrea B. Apolo, John Allan Ellerton, Jeffrey R. Infante, Manish Agrawal, Michael S. Gordon, Raid Aljumaily, Carolyn D. Britten, Luc Dirix, Keun-Wook Lee, Matthew H. Taylor, Patrick Schoffski, Ding Wang, Alain Ravaud, Junyuan Xiong, Galit Rosen, James L. Gulley, Manish R. Patel
Journal: Journal of Clinical Oncology (2019)

425 Background: Avelumab, a human anti‒PD-L1 IgG1 antibody, is approved for the treatment of metastatic urothelial cancer (mUC) progressing after platinum chemotherapy in the US, Canada, and Israel. Here, we report an updated pooled analysis of 2 cohorts of avelumab-treated patients (pts) with mUC from the JAVELIN Solid Tumor study (NCT01772004). Methods: Pts with mUC whose disease had progressed after platinum-based therapy or were cisplatin ineligible received avelumab 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (NCI CTCAE v4.0). Results: As of April 2018, 249 pts had received avelumab and had been followed for ≥2 years (median 2.7 years). Median treatment duration was 12.0 weeks (IQR, 6.0-32.1), and 12 pts (4.8%) remained on treatment. Confirmed ORR in all evaluable pts (n = 242) was 16.5% (95% CI: 12.1%-21.8%; complete response in 4.1%). Median DOR was 20.5 mo (95% CI: 9.7-not estimable), and the Kaplan-Meier (K-M) estimate of 12-mo DOR was 65.4% (95% CI: 47.0%-78.8%). Median PFS was 1.6 mo (95% CI: 1.4-2.7 mo), median OS was 7.0 mo (95% CI: 5.9-8.5 mo), and the K-M 12-mo and 24-mo OS rates were 35.9% (95% CI: 29.9%-42.0%) and 20.1% (95% CI: 15.2%-25.4%), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 71.1% of pts (177/249), most commonly infusion-related reactions (24.1%), fatigue (18.1%) and rash (18.1%). Grade ≥3 TRAEs occurred in 11.6% of pts (29/249), most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). Ten pts (4.0%) discontinued avelumab due to a TRAE. There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab showed durable clinical activity and had a manageable safety profile in pts with mUC. A phase 3 trial of avelumab in the maintenance setting after first-line platinum-based therapy for mUC is ongoing. Clinical trial information: NCT01772004.
Clinical Severity Correlates with in Vitro Residual Function of FANCB Missense Variants
Authors: Moonjung Jung, Ramanagouda Ramanagoudr Bhojappa, Ozgur Rosti, Francis P. Lach, Frank X. Donovan, Arleen D. Auerbach, Settara C. Chandrasekharappa, Agata Smogorzewska
Journal: Blood (2018)
Prevalence of clinically meaningful prognostic variability in cancer: An analysis using a new taxonomy system.
Authors: Andrew Pecora, Eric V Schultz, Kelly Choi, Augie Smith, Brian LaRock, Dhakshila Paramanathan, William T. DeRosa, Andre Goy, Edward J. Licitra, David Samuel DiCapua Siegel, Stuart L. Goldberg
Journal: Journal of Clinical Oncology (2015)

e17699 Background: Precise characterizations of tumor type to permit “precision” medicine are required for optimal outcomes and to facilitate payment reforms. ICD9 codes lump multiple cancer subtypes together (eg: all lung cancers ICD9 162.x). To enable comparisons of similar tumor types a new taxonomy system, amenable to computerized searching, has been created that embraces the complexity of cancer. Methods: The Cancer Outcomes Tracking & Analysis “nodal address” system (CNA) embodies a prospective assessment of characteristics (diagnostic, prognostic and disease status), mapping all clinically relevant scenarios into defined entities (each evidence based to be distinct). CNAs start with tumor type and assign additional markers based on characteristics. (eg: in breast cancer, stage is included in the CNA; hormone receptor status also influences treatment; however if ER+, the prognostic value of PR is trumped [therefore “ER+/PR irrelevant”]). Results: This expert panel grouping limited the number of CNAs from several trillion across all of oncology (if every combination were listed) to 517,422 entities. CNAs by cancer type: neuro-oncology 114,754, gastrointestinal 109,468, gynecologic 105,595, lymphoma 79,325, sarcoma 38,194, myeloma 23,949, head & neck 15,895, leukemia 9712, thoracic 8663, genitourinary 7117, breast 3061, non-malignant blood diseases 1031, unknown primary 379, and endocrine 261, demonstrating differing “prognostic complexity.” In 562 unselected breast cancer pts, 46% were assigned to 6 CNAs (all pts falling into 106 CNAs). The 6 common CNAs all involved adjuvant therapy, node negative, ER+, HER2 -, ECOG < 2, with 94 pts 5mm-5cm and Oncotype Dx 11-25, 51 pts DCIS histology, 34 pts 5mm-5cm and Oncotype Dx < 11, 32pts 5mm-5cm, age > 70, 26 pts 5mm-5cm, age < 70, and 21 pts 1mm-5mm. Rare CNAs were identified which can facilitate research subject identification. Conclusions: The CNA taxonomy sorts cancer by clinically relevant characteristics facilitating clinical/financial analytics of similar complex tumor types, unlike the lumped ICD 9 codes. Cancer types have differing prevalence of “theoretical” variability but “clusters” of CNAs encompass the majority of pts.
SUV max ratio as a novel prognostic factor in advanced colorectal cancer.
Authors: Victoria Sanchez, Jose Carlos Villa, Raquel Cervera, Lopez Rafael, Rocio Galan, Juana Maria Cano, Javier Espinosa
Journal: Journal of Clinical Oncology (2015)

e14520 Background: The clinical utility of fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan predicting the outcome of patients with metastatic colorectal cancer (mCRC) has not been yet well studied. We hypothesized the relationship between standardized uptake value (SUV) FDG-PET scan before and after treatment predicting outcomes among patients with mCRC. Methods: We retrospectively reviewed mCRC patients underwent FDG-PET scan prior treatment and measured metabolic activity in follow-up imaging at the University General Hospital of Ciudad Real (Spain). SUV max Ratio of the main metastatic lesion was calculated (SUV max post treatment / SUV max pre-treatment). Primary end points, time to treatment failure (TTF) and overall survival (OS) were stratified in low and high median SUV max ratio. TTF and OS were estimated by Kaplan Meier method. Survival probabilities were estimated by Cox proportional regression analysis. Results: The study population consisted of 94 patients (median age of 64 years). Median pretreatment SUV was 7,7 (range, 0,6-32,0), median post treatment SUV was 2,2 (range, 0,6-30,9) and the median SUX max ratio was 0,49 (0-4). There were differences in TTF (14 Vs 8 months) and OS (40 Vs 28 months) non statistically significant; but if we can establish a subgroup analysis, patients with metastatic hepatic lesions (N = 58) TTF was 13 Vs 7 months (p < 0.05) and OS was 42 Vs 17 months (p < 0.01); regarding extrahepatic disease (N = 36), no differences were found in OS and TTF rates. SUV ratio in metastases was a significant predictor for overall survival (hazard ratio 0.530, 95% confidence interval 0.282–0.996, P < 0.05). Conclusions: SUV max ratio could be a novel prognostic marker for advanced colorectal cancer patients receiving systemic therapy. Low SUV max ratio was associated with markedly longer OS and longer TTP.
Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease
Authors: Ceri Rowe, Alice J. Sitch, Jonathan Barratt, Elizabeth A. Brettell, Paul Cockwell, R. Neil Dalton, Jon J. Deeks, Gillian Eaglestone, Tracy Pellatt-Higgins, Philip A. Kalra, Kamlesh Khunti, Fiona C. Loud, Frances S. Morris, Ryan S. Ottridge, Paul E. Stevens, Claire C. Sharpe, Andrew J. Sutton, Maarten W. Taal, Edmund J. Lamb
Journal: Kidney International (2019)
Age-related racial/ethnic differences in the impact of targeted therapy and immunomodulatory agents on survival of patients with multiple myeloma: A population-based analysis.
Authors: Nay Min Tun, Elizabeth Guevara, Jean G. Ford
Journal: Journal of Clinical Oncology (2015)

e17604 Background: In clinical trials, targeted therapy and immunomodulatory agents significantly improved survival of patients with multiple myeloma, compared with traditional chemotherapy. However, the impact of such novel agents (NA) on overall patient survival and on racial disparities in survival, remains largely unknown. We performed a population-based analysis to address these questions. Methods: We queried the Surveillance, Epidemiology and End Results (SEER) 18 registry dataset from 1973 to 2011, to identify patients with multiple myeloma. We excluded patients based on these criteria: diagnosis at autopsy, unknown survival duration, and unknown race. We divided patients into two groups: pre-NA (PNA; 1973-2004) and NA (2005-2011). We analyzed data using chi-square test, Kaplan-Meier method, log-rank test, or Cox proportional hazards model as appropriate. Results: A total of 82,906 patients were eligible. Proportions of patients aged 65 and older varied by race/ethnicity: Non-Hispanic White (NHW) 66%, Hispanic 52%, Other 60%, and Black 53% (p < .001), with median age at diagnosis of 70, 65, 68 and 66 years, respectively. For the < 65-year age group, comparing the PNA and NA era, median survival increased by 33 months for NHW (47 to 80 months, p < .001), by 18 months for Hispanics (47 to 65 months, p < .001), by 28 months for Others (44 to 72 months, p < .001), and by 29 months for Blacks (43 to 72 months, p < .001). In this age group, Blacks had higher mortality rates during the PNA period, compared with NHWs (HR, 1.06; CI, 1.02, 1.11). This disparity persisted during the NA period (HR, 1.2; CI, 1.11, 1.29). By contrast, in the 65 and older group, median survival was improved by only 4-6 months across racial/ethnic groups (from 24-25 to 29-30 months, p = .01 to < .001) from the PNA to NA era. Conclusions: The impact of the novel agents was mainly observed in patients aged < 65 years. In this age group, the survival difference between NHWs and Blacks continued to exist from the PNA to NA era, and Hispanic patients experienced the smallest survival benefit from the novel agents. The causes of these disparities, though likely complex, require further investigation.
Hormonal and genetic factors prognosis in gastric cancer.
Authors: Dilshod Makhmudovich Egamberdiev, Mirjalol Djuraev, Doniyar Pulatov, Sanjarbek Khudayorov, Olimjon Imamov
Journal: Journal of Clinical Oncology (2015)

e15029 Background: Improve the efficiency of treatment for locally advanced gastric cancer (LAGC) by designing new methods of treatment, taking into account the status of molecular markers of sensitivity and resistance to cytotoxic drugs and hormonal status. Methods: The control group consisted of 30 patients with LAGC, whom in the first stage of treatment was performed operation. In the second stage of treatment, after 3-5 weeks after surgery patients received 2-4 cycles of postoperative (adjuvant) therapy by DCF regime (Docetaxel, Cisplatin, 5-FU) - 10 and CF (Cisplatin, 5-FU) - 20 patients. A study group comprised 27 patients with LAGC. In the study group were determined mutations of BRCA 1 and 2 genes, expression of ER and PR. In the study group patients underwent 2-4 cycles of neoadjuvant chemotherapy (NAC) by DCF regimen. In 8 (30%) of the main group were observed mutation of BRCA genes, and increased expression of ER and PR. In this group of patients in addition to chemotherapy there was used Tamoxifen 20 mg/day. Results: Patients who received NAC, after 2-4 cycles in 25% of hormone positive (HP) patients treated with Tamoxifen was observed complete regression (CR). In hormone negative (HN) patients CR was observed only in 16% cases. In HP patients disease progression (DP) cases were not observed, whereas in 2 HN cases there were noted DP. In general, the number of positive responses to NAC in both subgroups was approximately equal, about 50%. In 4 (21%) of HN patients there was observed DP during the adjuvant chemotherapy. In HP patients had 100% one-year survival rate, whereas in HN patients this figure was 94.7%. Significant superiority was noted in terms of disease free survival (DFS) in patients receiving NAC. In the main group 1 year DFS was above 25% and 2 year higher than 30% than in the group of patients treated with only adjuvant chemotherapy. Conclusions: Conducting of 2-4 cycles of preoperative (neoadjuvant) chemotherapy by DCF regimen in LAGC led to reduce the stage of the process in 48%, to perform radical surgery in 56% of patients and achieved 52% 2 years of DFS. Overcoming tumor resistance to treatment through the use of hormonal drugs will provide an opportunity to increase overall survival and progression-free survival, improve the quality of patient’s life.
A retrospective review of New Zealand patients with advanced ovarian cancer treated with dose dense chemotherapy.
Authors: Elliott Brenman
Journal: Journal of Clinical Oncology (2015)

e16552 Background: Combination chemotherapy with 3 weekly paclitaxel and carboplatin is an internationally recognized standard first line treatment for advanced epithelial ovarian cancer. In 2009 the Japanese Gynecologic Oncology Group (JGOG) conducted a phase III randomized controlled trial (JGOG 3016) comparing conventional 3 weekly treatments with weekly ‘dose dense’ paclitaxel in combination with 3 weekly carboplatin. The trial showed significant improvements in progression free survival and overall survival favoring dose dense treatment (PFS = 28.2 months vs 17.5 months (p = 0.0037), median OS = 100.5 months vs 62.2 months (p = 0.039)). Despite improved outcomes, the JGOG regimen has not been internationally adopted as standard. Toxicity led to frequent dose reductions, treatment delays and patient withdrawal. In addition the trial only recruited patients of Asian origin. It is unknown whether similar results will be observed in European populations due to genotypic and phenotypic differences. The Oncology Department at Waikato Hospital began offering ‘dose dense’ treatment for newly diagnosed advanced ovarian cancer from 2010 onwards. We now have the largest population of New Zealand patients treated with this regimen. We conducted a retrospective review examining outcomes and tolerability of ‘dose dense’ chemotherapy. Methods: Patients were identified using a chemotherapy database. Data was collected from electronic records, case notes, nursing notes, and prescription charts. Results: 48 patients were identified between March 2010 and March 2014. Median age was 62. 75% of patients had stage IIIc or IV disease. Median PFS was 24 months, with median OS not yet reached. 81% of patients experienced any grade 3 or 4 toxicity. However, only 19% of patients had grade 3 or 4 non-hematological toxicity. 46% of patients were still receiving weekly paclitaxel by the end of the sixth cycle. Conclusions: Our ‘real life’ experience suggests that treatment with JGOG style dose-dense chemotherapy is tolerable, and has PFS rates exceeding those reported for conventional 3 weekly regimens. Further studies are required to confirm if these results are reproducible in other centers within New Zealand.
Effect of the extent of lymph node dissection on overall survival in patients treated for oral cavity squamous cell carcinoma.
Authors: Jennifer Lobo Shah, Michael Kaplan, Vasu Divi, Quynh-Thu Le, Wendy Hara
Journal: Journal of Clinical Oncology (2015)

6075 Background: Limited recently published data has suggested that resection of at least 18 lymph nodes improves outcomes for patients treated with oral cavity cancer. We sought to determine if further survival benefit could be derived from a more extensive nodal dissection in these patients. Methods: We retrospectively reviewed 551 consecutive patients treated at the Stanford Cancer Institute from 1998-2013 for oral cavity squamous cell carcinoma with surgical resection followed by adjuvant therapy if indicated. Patients treated for recurrent disease and metastatic disease were not included. Of this cohort, 278 patients underwent neck dissection as a component of their initial surgical management. For this study, we defined a select neck dissection as 0-19 lymph nodes, a standard dissection as 20-39 lymph nodes, and a comprehensive dissection as 40 or more lymph nodes. Results: Within the 278 patients who underwent neck dissection, 85 patients had a select dissection, 100 patients had a standard dissection, and 93 patients had a comprehensive dissection. In this cohort, there was an overall survival benefit to having a comprehensive dissection compared to a select or standard dissection (p = 0.05). Of the patients who underwent adjuvant radiation therapy (RT), 24% had a select dissection, 35% had a standard dissection, and 40% had a comprehensive dissection. For patients who had RT, there was overall survival benefit to having a comprehensive dissection compared to select or standard (p = 0.05). This survival benefit was further seen patients with T2 and T3 tumors (p = 0.005, p = 0.04), N2 nodal involvement (p = 0.01), extracapsular extension (p = 0.04), and perineural invasion (p = 0.06). The extent of neck dissection did not impact survival for patients who did not undergo radiation therapy, even when analyzed by T and N stage. Conclusions: For patients requiring radiation therapy for oral cavity squamous cell carcinoma, a comprehensive neck dissection including the resection of at least 40 lymph nodes confers overall survival benefit.
Prospective evaluation of circulating tumor DNA sequencing in pancreatobiliary carcinomas.
Authors: Eric Andrew Collisson, Oliver Zill, Claire Greene, Jim Leng, LaiMun Siew, Mary A. Vu, Robin Kate Kelley, Andrew H. Ko, Chloe Evelyn Atreya, Katherine Van Loon, Trever Grant Bivona, Margaret A. Tempero, Dragan Sebisanovic, Pamela N. Munster, AmirAli Talasaz
Journal: Journal of Clinical Oncology (2015)

107 Background: Pancreatobiliary carcinomas (PC) carry a poor prognosis but have not yet benefitted from the revolution in precision oncology, in part because biopsy tissue is often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing tests may provide access to genetic testing and monitoring for advanced PC patients. Methods: Twenty-five advanced PC patients were enrolled prospectively in a trial to assess the feasibility, accuracy, and clinical utility of cfDNA next-generation sequencing (NGS) of 54 cancer genes. cfDNA mutations were compared to those detected by biopsy-based NGS tests, and the concordance of the two was determined. cfDNA sequencing in disease monitoring was compared to changes in secreted tumor markers in a subset of patients. Results: The NGS-based cfDNA test detected cancer mutations in 21 of 25 (84%) advanced PC patients and provided actionable findings for four patients. Multi-gene sequencing data was available from both blood-based and biopsy-based methods for 17 patients. Over 90% of mutations detected by the biopsy-based genetic tests were detected in cfDNA in these 17 evaluable patients. Four additional mutations were detected by cfDNA sequencing that were not detected in tumor tissue. Tumor biopsy NGS failed for 8 patients, equating to a considerably higher failure rate (32%) than the overall failure rate reported by commercial vendors. Three cfDNA mutations in these patients suggested a new therapeutic option. An activating EGFR-exon19 deletion was observed in cfDNA for one patient, which was later confirmed by a biopsy test and empowered successful treatment with erlotinib. The average diagnostic accuracy of cfDNA sequencing was 97%, with 92% average sensitivity and 100% specificity across the cohort. Changes in cfDNA mutation frequencies correlated with changes in tumor marker measurements (Pearson’s r = 0.7). Conclusions: cfDNA sequencing is a clinically practicable alternative to biopsy-based tumor DNA sequencing in PC. cfDNA from most PCs showed high mutational concordance with tissue biopsy, and showed high tumor-burden concordance with tumor markers. cfDNA sequencing should be considered for prospective therapeutic trials in pancreatobiliary cancers.
Mechanism of Action of a New Anti-CD38 Antibody: Enhancing Myeloma Immunotherapy
Authors: Fabio Malavasi, Angelo Corso Faini
Journal: Clinical Cancer Research (2019)

Antibody therapy is a treatment option for several diseases, including multiple myeloma. The logic behind it is relatively simple: A target molecule is selected because of its expression on tumor cells, and the antibody delivers cytotoxic effects. Therapeutic results in multiple myeloma indicate that the anti-CD38 antibodies may have relevant immunotherapeutic properties.See related article by Moreno et al., p. 3176.
Is cytoreductive nephrectomy necessary in metastatic renal cell carcinoma with primary kidney tumor in situ treated by sunitinib: Real-world data from a single Chinese center.
Authors: Wen-Hao Xu, Yuan-Yuan Qu, Hong-Kai Wang, Hai-Liang Zhang, Dingwei Ye
Journal: Journal of Clinical Oncology (2019)

570 Background: To evaluate the role of cytoreductive nephrectomy (CN), which was an indispensable treatment in metastasis renal cell carcinoma (mRCC), compared with cytokine treatment, we assessed the survival benefit of CN in patients with mRCC treated by sunitinib in targeted therapy era. Methods: This retrospective study compared the progression-free survival (PFS) and overall survival (OS) between mRCC patients who did or did not undergo CN. We screened out and enrolled patients from April 2006 to November 2013 as suitable candidates for CN with primary kidney tumor in situ. Logistic regression models were used to measure the effects of the clinical and pathological covariates. The Kaplan-Meier method and log-rank test were performed to evaluate the possible survival differences between two groups. Results: Atotal of 70 patients were assigned to undergo CN followed with sunitinib and 48 received sunitinib alone. According to the survival analysis, the median PFS was 8.38 months and the median OS was 15.48 months, with 109 deaths observed. There were no significant difference between CN-sunitinib group and sunitinib-alone group in both PFS(7.2 versus 11.6 months, 95% confidence interval, 5.3 to 11.8; P= 0.525) and OS (16.7 versus 15.2 months, 95% confidence interval, 12.0 to 18.9, P= 0.839). However, stratified analysis revealed that PFS and OS might decrease after CN in the subgroups of patients with IMDC prognostic criteria of high-risk disease (PFS: 4.4 [95% CI, 3.5 to 5.3] vs. 6.3 [95% CI, 5.3 to 7.2]months, P= 0.002; OS: 8.8 [95% CI, 7.0 to 10.6] vs 9.9 [95% CI, 10.0 to 11.8] months, P= 0.011) and those with lymphatic metastasis (PFS: 4.4 [95% CI, 2.9 to 6.0] vs. 6.6 [95% CI, 2.1 to 11.2] months, P&lt; 0.001; OS: 8.8 [95% CI, 6.9 to 10.7] vs 9.9 [95% CI, 7.1 to 10.7] months, P= 0.006). Conclusions: Cytoreductive nephrectomy may offer no survival benefits in those mRCC patients with primary kidney tumor in situ, and moreover, sunitinib-alone therapy perhaps contributes longer PFS and OS for the patients with IMDC high-risk disease and those with lymphatic metastasis.