tbuckley/cabot-search huggingface dataset:
Targeting advanced pancreatic cancer with activated t cells armed with anti-CD3 x anti-EGFR bispecific antibody.
Authors: Lawrence G. Lum, Minsig Choi, Tri Minh Le, Archana Thakur, Abhinav Deol, Karen K. Ballen, Leonid Volodin, Tamila L. Kindwall-Keller, Qin Liu, Gregory Dyson, Anthony Frank Shields
Journal: Journal of Clinical Oncology (2018)

4108 Background: Conventional chemotherapy (CT) for advanced pancreatic cancer (PC) is associated with dismal response rates and poor survival. Arming anti-CD3 activated T cells (ATC) with anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) makes every ATC into a non-MHC-restricted EGFR-specific cytotoxic T lymphocyte. Engagement of CD3 on T cells and EGFR on PC cell lines leads to cytokine secretion, proliferation, cytotoxicity by ATC, and inhibition of tumor growth. Methods: We report on 9 LAPC and MPC patients (pts) (5 phase I and 4 phase I/II pts). In our phase I study at Karmanos Cancer Institute (KCI) on NCT0140874, EGFRBi-armed T cells (EGFR BATs) were used to target EGFR in 5 pts with unresectable or metastatic PC in a phase I dose escalation involving 3 weekly infusions of 10, 20, and 40 x 109 BATs per infusion followed by a booster infusion 3 months later for up to 80 x 109 BATs if they were stable or better. In a phase II study performed at KCI on NCT02620865 and continued at the University of Virginia (UVA) on NCT03269526, 4 pts received two infusions per week of 1010 EGFRBi BATs for 4 weeks for a total of 8 x 1010. Results: Following the BATs infusions in the phase I study at KCI, one pt was stable for 6.5 months and 2 pts who progressed after the infusions developed complete responses (CRs) to subsequent CT. Remarkably, pt IT20104 who was stable for 1 year on capecitabine had a “flare” or “pseudoprogression” after 3 BATs infusions, but subsequently achieved a CR to capecitabine and has been off therapy for 1 year (40.8 months after enrollment). The median overall survival (OS) in 5 pts was 31.0 months [13.6, 14.5, 31.0, 40.8 (CR) and 42.5 months after enrollment] with the median time to progression (TTP) of 7.0 months. In summary, 5 of 5 pts in the phase I survived > 1 year. In the phase II study, two pts have stable disease at 2.3 and 21.5 months, respectively. The median OS is 31.0 months for all 9 patients. Conclusions: While these patients are selected, these results are promising. Targeting PC with EGFR BATs may have improved OS in a small series of pts. The series provides evidence for anti-tumor activity of EGFR BATs, and, in addition, the BATs infusions may enhance tumor responses to subsequent CT. Clinical trial information: NCT01420874.
Clinical impact of nodal status on survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with gastric peritoneal metastasis.
Authors: Pierre Emmanuel Bonnot, Frederic Mercier, Mohammad Alyami, Jean Marc Bereder, Karine Abboud, François Quenet, Diane Goere, Pierre Meeus, Simon Msika, Catherine Arvieux, Jeremie H. Lefevre, Denis Pezet, Romuald Wernert, Patrick RAT, Nicolas Pirro, Thomas Courvoisier, Reza Kianmanesh, Frederic Marchal, Marc Pocard, Olivier Glehen
Journal: Journal of Clinical Oncology (2018)

e16093 Background: Lymph node status (LNS) drives prognosis of gastric cancer. Peritoneal carcinomatosis (PC) is a stage IV regardless of the LNS and associated with poor prognosis. For selected patients, hyperthermic intraperitoneal chemotherapy (HIPEC) represents a potentially curative treatment. The clinical impact of LNS remains unclear for such patients. Methods: Data from 172 patients who underwent complete cytoreductive surgery including a D2 lymphadenectomy and HIPEC for gastric cancer with PC, in 16 French centers from 1989 to 2014, were collected. The 7th edition of pathologic TNM stages was used to define the LNS. Survival was calculated from surgery. The log-rank test was used to compare survivals and Cox models to identify the prognostic factors in univariate and multivariate analyses. Results: Median age was 51.4 years. 72 patients had a plastica linitis. 69.2% of tumors had a signet ring cells component. Median number of resected lymph nodes was 24 (5-67). pN0, pN1, pN2 and pN3 represented respectively 21.5%, 13.4%, 15.1% and 50% of patients. 65.1% received a neoadjuvant chemotherapy: 86.5% in the pN0 subgroup versus 59.3% in the pN1-2-3 subgroup (P = .002). 49.8 % received an adjuvant treatment. LNS was not influenced by the extension of the PC as median Peritoneal Cancer Index was similar in each group (6 in the whole population). 1-, 3- and 5-year survivals in the whole cohort were 69.3%, 27.4% and 20.2%, respectively. Median overall survival was 19.4 months. pN3 status was associated with worse survival. Median survivals in the pN0, pN1, pN2 were 23.2, 29.4, 23.9 months respectively whereas it was 13.2 months in the pN3 subgroup (p = .004). For synchronous PC (n = 138), 3- and 5-year OS for the pN0-1-2 and pN3 groups were 31.6% and 29.7% v 15.7% and 7.8%. In multivariate analysis, plastica linitis (HR: 2.565) and absence of neodajuvant therapy (HR: 2.396) were associated with a pN3 LNS. Conclusions: In gastric cancer with PC treated by HIPEC, the prognostic impact of LNS is less important than in non-metastatic tumors. There is no clinical benefit of a pN0 status compared to a pN1-2 status. Only pN3 status is associated with worse oncological outcomes.
Rituximab maintenance for mantle cell lymphoma: A meta-analysis.
Authors: Talal Hilal, Zhen Wang, Diana Almader-Douglas, Allison Claire Rosenthal, Craig B. Reeder, Tania Jain
Journal: Journal of Clinical Oncology (2018)

e19557 Background: The role of rituximab maintenance (RM) in mantle cell lymphoma (MCL) is unclear. Currently, rituximab is not an FDA approved therapy for this indication. We conducted a systematic review and meta-analysis to evaluate outcomes of RM compared to non-RM in patients with MCL. Methods: We searched 5 databases including PubMed, Embase, Scopus, Web of Science, and Cochrane from inception to October 2017 for randomized controlled trials (RCTs) and observational studies evaluating the use of RM, compared non-RM after induction chemoimmunotherapy (CIT) in patients with MCL. Prespecified data elements were extracted from each study. Outcomes of interest included progression-free survival (PFS) and overall survival (OS). The overall effect was pooled using the DerSimonian-Laird random effect models. Results: We identified 697 records, 28 full-text articles were assessed for eligibility after exclusions. Seven studies with a total 1,050 patients met inclusion criteria, including 3 RCTs and 4 observational studies with comparative arms. Of these, 455 patients were in the RM arm, and 595 patients in the non-RM arm. Overall, RM improved PFS (HR 0.39, 95% CI 0.31 – 0.50) and OS (HR 0.47, 95% CI 0.27 – 0.83). These results persisted when restricting the analysis to patients treated after autologous SCT: PFS (HR 0.34, 95% CI0.25 – 0.47) and OS (HR 0.38, 95% 0.22 – 0.65). When restricting the analysis to prospective RCTs only, RM improved PFS (HR 0.47, 95% CI 0.34 – 0.65) but not OS (HR 0.70, 95% CI 0.46 – 1.08). However, only 2 of the 3 RCTs reported OS; one used RM after induction with fludarabine-based or cyclophosphamide-based chemotherapy in the elderly (70 y), and one used RM after induction with cytarabine-based chemotherapy and autologous SCT in younger patients (57 y). Conclusions: In this meta-analysis, RM improved PFS and OS in patients with MCL after induction CIT. This benefit is especially significant after autologous SCT.
Apatinib for patients with unresectable high-grade osteosarcoma progressing after standard chemotherapy: A multi-center retrospective study.
Authors: Wenxi Yu, Xiuchun Yu, Sujia Wu, Lina Tang, Shui'er Zheng, Yan Zhou, Yujing Huang, Guowei Qian, Hongtao Li, Jianjun Zhang, Aina He, Yonggang Wang, Haiyan Hu, Feng Lin, Zan Shen, Yang Yao
Journal: Journal of Clinical Oncology (2017)

11031 Background: Prognosis for patients with relapsed/metastatic osteosarcoma is dismal and the optimal treatment strategy remains to be refined. Sorafenib and sorafenib plus everolimus are the only two second-line targeted therapies recommend by FDA. The median progression-free survival (PFS) was 4–5 months. In this study, the efficacy and safety of apatinib, another oral tyrosine kinase inhibitor targeting VEGFR-2, were evaluated in patients (pts) with inoperable high-grade osteosarcoma progressing after standard multidisciplinary treatment. Methods: This retrospective study reviewed the medical records of 26 pts with metastatic osteosarcoma who received apatinib at a dose of 500 mg qd or 250 mg bid after failure of standard treatment including doxorubicin, cisplatin, ifosfamide and high-dose methotrexate from Jul 2015 to Nov 2016. Results: Among all pts, 25 (96.2%) had pulmonary metastases and 4 (15.4%) had metastases in the bone (Table). Eleven pts achieved partial response, 10 stable disease and 5 progressive disease, yielding an objective response rate of 42.3% and a clinical benefit rate of 80.8%. Followed up to Dec 31 2016, the median PFS was 8 months (95%CI, 3.2–12.8 months), and the median overall survival (OS) was not reached. The 12-month PFS and OS rates were 22.5% (95%CI, 1.6%–58.1%) and 68.7% (95%CI, 37.5%–86.5%), respectively. Noteworthy, the 12-month PFS rate for patients treated with apatinib in the second-line setting was 51.3% (95%CI, 9.1%–83.1%). The most frequent treatment-related adverse events (AEs) were hand-foot skin reaction (HFSR) (84.6%), hypertension (46.2%), and diarrhea (23.1%). Severe AEs included grade 3 HFSR (7.7%) and hypertension (3.8%). No unexpected AE was found. Conclusions: Apatinib was well tolerated and demonstrated activity as a second- or later-line treatment in patients with metastatic osteosarcoma, which deserves further investigations. [Table: see text]
Baseline total metabolic volume (TMTV) to predict the outcome of patients with advanced Hodgkin lymphoma (HL) enrolled in the AHL2011 LYSA trial.
Authors: Rene-Olivier Casasnovas, Salim Kanoun, Ilan Tal, Anne-Segolene Cottereau, Veronique Edeline, Pauline Brice, Reda Bouabdallah, Gilles A. Salles, Aspasia Stamatoullas, Jehan Dupuis, Oumedaly Reman, Thomas Gastinne, Bertrand Joly, Kamal Bouabdallah, Emmanuelle Nicolas-Virelizier, Marc Andre, Nicolas Mounier, Christophe Ferme, Michel Meignan, Alina Berriolo-Riedinger
Journal: Journal of Clinical Oncology (2016)

7509 Background: The TMTV assessed on the baseline FDG-PET is a novel approach of tumor burden measurement. It has been reported to influence HL outcome in a retrospective series (Kanoun, EJNM 2014). We designed a study evaluating the TMTV prognosis value in patients (pts) prospectively enrolled in a phase III randomized trial testing a treatment strategy driven by PET, compared to a standard treatment not monitored by PET. Methods: Eligible pts had to be enrolled in the AHL2011 trial (NCT01358747) and to have a baseline PET (PET0) available for central review and TMTV calculation. Pts were 16-60 y, with a previously untreated advanced HL (Ann Arbor stage III, IV or high risk IIB) and were randomly assigned to a treatment strategy driven by PET after 2 escalated BEACOPP (BEA) cycles (PET2), delivering 4 cycles of ABVD for PET2- pts and 4 cycles of BEA for PET2+ pts or a standard treatment not monitored by PET and delivering 6 cycles of BEA. PET2 were centrally reviewed and interpreted according to Deauville criteria. TMTV was computed on PET0 by summing the metabolic volumes of the individual lesions using the 41% SUVmax thresholding method already described in lymphoma. Results: 392 pts with a median age of 30 y were included: 64% were male, 89% had stage III/IV, and 59% an IPS ≥ 3. Median TMTV was 200 ml (23 – 2149). Using a X-tile method a 350 ml cut off value was identified from a training set (n = 262) and confirmed in a validation set (n = 130) of pts obtained from the whole series. With a 16 months median follow up, 2y-PFS was 81% vs 93% in pts with high and low TMTV respectively in the whole population (p = 0.0015; HR = 3). PET2 positivity was also related to a lower 2y-PFS compared to PET2- pts (76% vs 92%; p < 0.0001). Then 3 groups could be identified: pts with either [high TMTV and PET2+ (n = 23; 6%)], or [high TMTV and PET2-, or low TMTV and PET2+ (n = 103; 27%)], or [low TMTV and PET2- (n = 261; 67%)] had a 61%, 88%, 94% 2y-PFS respectively (p < 0.0001). Conclusions: TMTV predicts the outcome of young advanced HL pts independently of the early metabolic response to treatment. The combination of TMTV and PET2 allows identifying 3 subsets of HL pts with significantly different outcome that may help clinician to better tailor therapy. Clinical trial information: NCT01358747.
Relationship between protein biomarkers of potential chemotherapy response and microsatellite status in 28,101 cancer patients.
Authors: Mina Nikanjam, David Arguello, Zoran Gatalica, Donald A. Barkauskas, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2018)

e24259 Background: Immune-based (anti-PD-1/PD-L1) combinatorial therapy is being explored in many clinical trials. While microsatellite instability high (MSI-H) status predicts immunotherapy response, an improved understanding of how MSI-H relates to biomarkers potentially predicting chemotherapy sensitivity may be informative for cytotoxic/immunotherapy combinations. Methods: MSI status (next generation sequencing) and protein expression (immunohistochemistry) predictive of chemotherapy response (ERCC1, MGMT, RRM1, TOP2A, TOPO1, TS, TUBB3) were evaluated (Caris Life Sciences; CLIA lab). Associations were analyzed with the Mantel-Haenszel chi-squared test using tumor type as stratification. Results: Overall, 28,101 patient specimens encompassing 33 tumor types had a reportable MSI result. MSI-H status correlated with ERCC1, RRM1, TOP2A, TOPO1, and TUBB3 after controlling for tumor type (see Table). TS could not be evaluated by the Mantel-Haenszel test but was significant in 9/33 tumor types using Fischer’s exact test; MSI-H was associated with TS positivity (5-fluoruracil resistance) in these nine tumor types. MSI-H occurred more often with decreased ERCC1 expression (potential platinum benefit), TOP2A over-expression (potential doxorubicin/epirubicin benefit), and decreased TUBB3 expression (potential taxane benefit). MSI-H occurred less often with TOPO1 over-expression (marker of irinotecan response) and more frequently with RRM1 over-expression (marker of gemcitabine resistance). Conclusions: MSI-H solid tumors are associated with protein markers that may predict chemotherapy response, corroborating the administration of platinums, taxanes, doxorubicin or epirubicin in combination with checkpoint inhibitors. Immunotherapy combinations with gemcitabine or irinotecan may be less often effective. Biomarker Odds Ratio (OR) 95% CI p-value Potential benefit in combination therapy [Y/N] ERCC1 0.68 0.55 – 0.85 0.0005 platinums [Y] MGMT 0.91 0.62 – 1.31 0.59 -- RRM1 3.5 2.02 – 4.19 < 0.0001 gemcitabine [N] TOP2A 2.67 1.94 – 3.69 < 0.0001 doxorubicin/epirubicin [Y] TOPO1 0.78 0.67 – 0.90 0.0009 irinotecan [N] TUBB3 0.72 0.61 – 0.84 < 0.0001 taxanes [Y]
The incidence of other malignancies before and after sarcoma diagnosis: A population-based study.
Authors: Winette T.A. Van Der Graaf, Husson Olga, Willem J. van Houdt, Ingrid M.E. Desar, Vincent K.Y. Ho
Journal: Journal of Clinical Oncology (2017)

11076 Background: Sarcomas encompass a group of rare and heterogeneous mesenchymal malignancies with mostly unknown origin. Both exogenous risk factors, in particular radiotherapy, as well as genetic risk factors have been described. Second tumors next to sarcomas suggest associated risk factors. In the current study, we investigate the incidence of sarcomas and other malignancies by using population-based data from the Netherlands Cancer Registry. Methods: In 29,638 patients diagnosed with sarcoma between 1989 and 2015, with a median age of 59 years, we quantified the risk of other malignancies after sarcoma diagnosis using standardized incidence ratios (SIRs). In assessing associations with malignancies before sarcoma diagnosis, we focussed on previous radiotherapy. Skin carcinomas, with the exception of melanomas, were excluded. Results: In total, 3,381 (11.4%) sarcoma patients, median age 71years, had a previous malignancy (at a median age of 66 years). The most frequent sarcomas associated with prior tumors were angiosarcoma (34.5%) and gastrointestinal stromal tumours (20.6%). In the angiosarcoma group, 78.6% of patients had received prior radiotherapy for their previous tumors. Subsequent tumors (diagnosed in patients with median age of 69.5 years) after sarcoma diagnoses were detected in 2,523 patients with median age of 63 years (SIR 1.13; 95%CI: 1.09–1.18). Risks appear notably elevated for breast cancer (SIR 1.19; 95%CI: 1.06–1.34), lung cancer (SIR 1.15; 95%CI: 1.04–1.27), cancers of the urinary tract system (SIR 1.33; 95%CI: 1.14–1.53) and hematological cancers (SIR 1.31; 95%CI: 1.13–1.51). Median time until diagnosis of subsequent cancer was 52.7 months. Conclusions: Sarcoma patients have a markedly increased risk on another malignancy, either before or after the sarcoma diagnosis. Further research into genetic and exogenous risk factors may help to explain the associations.
Gaps in palliative care provision among the Indian cancer centres.
Authors: Anuja Damani, Jayeeta Chowdhury, Arunangshu Ghoshal, Jayita Deodhar, Mary Ann Muckaden, C S. Pramesh, Naveen Salins
Journal: Journal of Clinical Oncology (2018)

e22181 Background: The National Cancer Grid (NCG) of India is a union of cancer centres that provides uniform standards for cancer care and conducts collaborative clinical research. It has been envisaged to develop an integrated palliative care services across the NCG cancer centres. The aim of this study was to identify the gaps in palliative care provision in the NCG cancer centres. Methods: Cross sectional survey was conducted using a validated web-based questionnaire. The survey questionnaire had 7 sections related to capacity, drug availability, education, policy, advocacy, and quality assurance. Results: Out of the 102 NCG cancer centres invited to participate, 89 centres participated in the survey. Palliative care outpatients service was available in 68.1% of the centres. However, trained palliative care physicians was available in 34.1% of the centres. Less than three-fourth of these physicians have > 1 year of training and only 50% of nurses have < 6 weeks palliative care training. 69.2% of centres do not have social workers, 60.4% do not have counsellors, and 76.9% do not have volunteers. 84.3% of the centres have license to procure, store and dispense opioids and 77.5% of the centres have uninterrupted supply of oral Morphine. Only 38.5% of the centres provide home based palliative care services. 44% of the centres have access for hospice services and 66.3% have facilities for in-patient palliative care. 61.5% of the centres do not have dedicated funds for palliative care and 23.1% of the centres reported lack of support from the hospital administration. End of life care is seldom recognised, and there is a lack of institutional policy towards end of life. Very few centres took part in quality assurance activities. Conclusions: Most of the NCG centres have facility to provide palliative care but suffer from lack of funding and manpower. There is a need of greater quality and outcome assessment in the centres.
Identifying candidates for prednisone to dexamethasone switch amongst patients with castration-resistant prostate cancer undergoing abiraterone therapy.
Authors: Vanessa Sarah Arciero, Kelly Lien, Erica McDonald, Esther K. Lee, Phillip Stanley Blanchette, Urban Emmenegger
Journal: Journal of Clinical Oncology (2016)

e16568 Background: Abiraterone plus prednisone (AA+P) delays symptomatic progression, palliates symptoms, and improves survival of pts with castration-resistant prostate cancer (CRPC). While inherent or acquired therapeutic resistance limits the benefit of AA+P, emerging data suggest that a switch from prednisone to dexamethasone (D) may achieve durable biochemical responses in CRPC pts progressing on AA+P. Methods: To better understand who may benefit from a steroid switch, we analyzed the outcome of pts switched to AA+D upon biochemical progression on AA+P, among CRPC pts treated at Sunnybrook Odette Cancer Centre, Toronto, Canada. Pts were included if they had undergone AA+D therapy (D 0.5 or 1.0 mg po daily) for at least 12 weeks. Results: 18 pts fit the inclusion criteria, of which 11 were chemotherapy-naïve, and 7 had received prior docetaxel. None had received P or D monotherapy previously. 8 pts (44%) achieved a > 50% PSA reduction with AA+P (PSA50), and 3 pts (17%) had a > 30% PSA response (PSA30). In 6 pts (33%) we found PSA stabilization (PSA-SD) as best response, whereas 1 pt (6%) biochemically progressed on AA+P. Mean (±SD) AA+P treatment duration was 213.44 (±151.24) days. Upon switch to AA+D, 5 pts (28%) achieved a PSA50, 1 pt (6%) a PSA30, PSA remained stable in 11 pts (61%), and 1 pt (6%) progressed biochemically. 6 pts are still continuing on AA+D after a median follow-up of 278 days. Amongst 11 AA+P responders (ie PSA50 or PSA30), 4 pts also achieved a sustained PSA50 on AA+D (202, 251, 399+, 587+ days), and 1 pt a PSA30 (274+). By contrast, only 1 of the 7 AA+P non-responders (14%) achieved a PSA response. Prior docetaxel did not affect the response to steroid switching. No unexpected adverse events were observed. Further data is being collected prospectively. Conclusions: In these mostly chemotherapy-naïve CRPC pts undergoing AA therapy, switching from P to D resulted in sustained PSA50 or PSA30 in 33% of pts. Whereas responses were seen in 5 of 11 pts (45%) with prior response to AA+P, the benefit of a P to D switch seems to be very limited in pts without prior response to AA+P.