tbuckley/cabot-search huggingface dataset:
Robotic vs. laparoscopic vs. open abdominoperineal resection for low rectal cancer: Short-term outcomes of a single-center prospective randomized controlled trial.
Authors: Ye Wei, Jianmin Xu, Li Ren, Qingyang Feng, Guodong He, Jingwen Chen, Wenju Chang, Dexiang Zhu, Tuo Yi, Qi Lin
Journal: Journal of Clinical Oncology (2017)

3603 Background: Currently, robotic surgery for rectal cancer using da Vinci System is common. However, there is almost no clinical trial reported. This randomized controlled trial aims to compare the safety and efficacy of robotic, laparoscopic and open abdominoperineal resection (APR) for low rectal cancer. Methods: From September 2013 to August 2016, patients aged from 18 to 75 years, with low rectal cancer within 5 cm from anal verge, clinical T1 to T3, no distant metastases, were randomly assigned to receive either robotic procedures (RAP), laparoscopic procedures (LAP) or open surgery (OS) for APR in 1:1:1 ratio. The primary endpoint was postoperative complication rate. This study is registered with ClinicalTrials.gov (NCT01985698). Results: Totally 406 patients were randomly assigned. Actually, 135 finished RAP, 131 finished LAP, and 137 finished OS (including 4 convert from LAP to OS). RAP had significantly lower postoperative complication rate (11.1%) than both LAP (21.4%, P = 0.023) and OS (27.7%, P = 0.001). Also, RAP reduced intraoperative hemorrhage (median [interquartile range], 100 [90-110] ml) than LAP (130 [100-150] ml, P &lt; 0.001) and OS (150 [120-260] ml, P &lt; 0.001). And RAP promoted postoperative recovery, with shorter days to first flatus (1.0 [1.0-2.0] day) than LAP (2.0 [2.0-3.0] day, P &lt; 0.001) and OS (3.0 [2.0-4.0] day, P &lt; 0.001), shorter days to first automatic urination (2.0 [2.0-3.0] day) than LAP (3.0 [2.0-4.0] day, P &lt; 0.001) and OS (3.0 [2.0-4.0] day, P &lt; 0.001), and shorter days to discharge (5.0 [5.0-6.0] days) than LAP (6.0 [5.0-7.0] days, P &lt; 0.001) and OS (6.0 [5.0-7.0] day, P = 0.005). There was no significant difference in open conversion rate, resection margin involvement (including circumferential resection margin), number of lymph node harvested and pathological tumor stage. Conclusions: Robotic APR was safer, and reproduce equivalent surgical quality of conventional laparoscopic and open surgery. Also, it provided less injury and faster functional recovery. Clinical trial information: NCT01985698.
Different pCR rates according PAM50 defined subtypes in HER2 positive early breast cancer treated with neoadjuvant pertuzumab and trastuzumab.
Authors: Tamara Diaz-Redondo, Rocío Lavado-Valenzuela, Begona Jimenez Rodriguez, TomÃ¡s Pascual, Fernando Galvez Montosa, Alejandro Falcon, Maria Carmen Álamo de la Gala, Cristina Morales-Estevez, Marta Amerigo Góngora, Javier Pascual, Nuria Ribelles, Macarena González Guerrero, Aurora Laborda Illanez, Luis Vicioso, Aranzazu Fernández, Nuria Chic, Jose Manuel Jerez, Martina Álvarez, Aleix Prat, Emilio Alba
Journal: Journal of Clinical Oncology (2018)

e12634 Background: We aim to compare the benefit of adding pertuzumab (P) to the standard neoadjuvant treatment with trastuzumab (T) in patients (pt) with early immunohistochemically (IHC) defined HER2+ breast cancer (BC) in the different intrinsic molecular subtypes defined by PAM50 gene expression analysis. Methods: 219 pt. with IHC HER2+ BC, stage I-IIIC, diagnosed in 8 Spanish hospitals were consecutively treated with neoadjuvant chemotherapy (NAC) + antitargeted HER2 therapy. Cohort A (n128) received NAC+T and Cohort B (n91) received NAC+T+P. Patients were classified into intrinsic molecular subtypes based on the PAM50 signature. Rate of pathologic complete response in breast and axilla (pCR) in the different subtypes was compared by ChiSquared test. A multivariate logistic regression model was used to analyze the potential effects of the covariates over the pCR rates. Results: Characteristics of the patients and intrinsic molecular subtypes are shown in Table 1. The overall pCR rate was significantly higher in cohort B vs A (66%vs39%, p = 0,0002). The pCR rate in the HER2E was 50% for T and 77% for T+P (p = 0,002) and 11% for T and 54% for T+P (p = 0.0007) in Luminals. In the multivariate analysis, the improvement pCR rates was highly associated with cohort (p = 0.00015, OR:3.22) and was not related to clinicopathologic covariates (p > 0.05). These results were confirmed for the HER2E subtype (p = 0.00168, OR:3.11) and more strongly for Luminals (p = 0.0045, OR:23.35). Conclusions: The highest pCR was reached by the PAM50 HER2E patients treated with T+P. In Luminal subtype the improvement of pCR is strongly associated with the used of pertuzumab and this association is independent of clinical covariates. Table 1. Clinicopathologic characteristics of pt T+NCT (n128) T+P+NCT (n91) Median age (range) 52 (29-83) 51 (30-77) n (%) n (%) Ki67 < 14% 11 (9) 4 (4) 15-50% 58 (45) 61(67) > 50% 24(19) 22 (24) Unk 35(27) 4 (4) HR + 89 (70) 56 (62) - 39 (30) 35 (38) PAM50 Sub HER2E 88 (69) 53 (58) Lum B 19 (15) 15 (17) Lum A 16 (12) 13 (14) Basal like 2 (2) 10 (11) Normal like 3 (2) 0 T T1 23 (18) 12 (13) T2 75 (59) 50 (55) T3 12 (9) 19 (21) T4 10 (8) 10 (11) Tx 8 (6) Node - 54 (42) 31 (34) + 74 (58) 60 (66)
Pembrolizumab plus chemoradiation vs chemoradiation alone for locally advanced head and neck squamous cell carcinoma: The phase 3 KEYNOTE-412 study.
Authors: Jean-Pascal H. Machiels, Lisa F. Licitra, Yungan Tao, Chia-Jui Yen, Danny Rischin, John Waldron, Barbara Burtness, Vincent Gregoire, Sanjiv S. Agarwala, Jeffrey Yorio, Jean-Pierre Delord, Sercan Aksoy, Sadakatsu Ikeda, Ruey-Long Hong, Joy Yang Ge, Holly M. Brown, Behzad Bidadi, Lillian L. Siu
Journal: Journal of Clinical Oncology (2018)

TPS6094 Background: Preclinical data in murine cancer models show improved tumor growth control and survival when radiation therapy (RT) is combined with a PD-1 inhibitor. Pembrolizumab is effective for treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), and initial results from a phase 1b study suggest that pembrolizumab plus chemoradiation therapy (CRT) is tolerable in patients with locally advanced (LA) HNSCC. KEYNOTE-412 (NCT03040999) is a phase 3, randomized, placebo-controlled, double-blind trial to determine efficacy and safety of pembrolizumab given with CRT and as maintenance therapy vs placebo plus CRT in LA-HNSCC. Methods: Patients will be randomly assigned (1:1) to receive pembrolizumab 200 mg every 3 weeks plus cisplatin-based CRT or placebo plus cisplatin-based CRT. Treatment will be stratified by RT regimen (accelerated RT [56-70 Gy, 6 fractions/week for 6 weeks] or standard RT [56-70 Gy, 5 fractions/week for 7 weeks]), tumor site/p16 status (oropharynx p16 positive vs p16 negative or larynx/hypopharynx/oral cavity), and disease stage (III vs IV). Priming dose of pembrolizumab or placebo will be given 1 week before CRT, followed by 2 doses during CRT, and an additional 14 doses after CRT, for a total of 17 pembrolizumab or placebo infusions. Eligibility criteria include age ≥18 years; newly diagnosed, treatment-naive, oropharyngeal p16–positive (any T4 or N3), oropharyngeal p16–negative (any T3-T4 or N2a-N3), or larynx/hypopharynx/oral cavity (any T3-T4 or N2a-N3) SCC; evaluable tumor burden (RECIST v1.1); and ECOG performance status 0-1. Treatment will be discontinued at the time of centrally confirmed disease progression, unacceptable toxicity, or patient/physician decision to withdraw. Patients will be evaluated to determine the necessity of neck dissection 12 weeks after completion of CRT. The primary end point is event-free survival. Secondary end points are overall survival, safety, and patient-reported outcomes. Relationship between biomarkers and clinical activity will be included as an exploratory end point. Recruitment is ongoing in 21 countries and will continue until ~780 patients are enrolled. Clinical trial information: NCT03040999.
Combination of CDK and Bcl-2 inhibitors in the treatment of soft-tissue sarcomas.
Authors: Xavier Garcia del Muro, Miriam Fuentes-Guirado, Roser López-Alemany, Aida Pérez-Contreras, Nuria Mulet, Silvia Garcia-Monclús, Oscar M. Tirado, Santi Rello-Varona
Journal: Journal of Clinical Oncology (2018)

11582 Background: Soft tissue sarcomas (STSs) present high mortality rates when metastatic and therefore identification of new active therapies is needed. Dinaciclib is a promising CDK inhibitor under evaluation in clinics, targeting principally CDK1 and CDK9 (involved in cell cycle and transcription regulation). BH3-mimetics are a promising new class of pro-apoptotic drugs for cancer treatment. Methods: We analyzed the response to Dinaciclib in a series of different STSs established cell lines, as apoptotic induction visualized in Flow Cytometry. Cell lines were categorized as Dinaciclib-sensitive and Dinaciclib-tolerant. Differences were studied by relevant protein expression changes during treatment leading to hypothesis proposal for key regulators. Validation of targets was performed by siRNA technology prior to engage in drug combination testing. In vivo experiments encompassed drugs safety and effectivity. Results: Dinaciclib induced apoptotic cell death, with important differences in the extent and timing among cell lines. Liposarcoma 402-91 was the most sensitive (cell death > 75% after 72 h), whereas leiomyosarcoma SK-LMS-1 was highly tolerant to Dinaciclib (cell death < 25%). Major partners in cell cycle and apoptosis induction signaling networks were affected by Dinaciclib treatment. The inhibition status of anti-apoptotic protein Bcl-xL was identified as the main determinant of the rhythm and extent of apoptosis triggering. In vitro combination of Dinaciclib with chemical Bcl-xL inhibitors (ABT-747 and A-1331852) overcame tolerance and triggered massive cell death in cultures (95% of cell death after 24 h). Once safely scalated to mice experimentation, drug combination effectiveness on mice engrafted tumors is currently ongoing. Conclusions: CDK inhibitors are active in STSs cell lines. The inhibition status of Bcl-xL can be considered as a predictor of Dinaciclib sensitivity in STS. Combinatorial strategies with CDK inhibitors and BH3-mimetics are worth examination as a new proposal for STS treatment.
Ethnic differences in pegfligrastim onpro kit (on-body injector) use among cancer patients.
Authors: Valerie Relias, Douglas W Hackenyos, Komal Wasif, Patricia Healey, Melissa H Smith, Wasif M. Saif
Journal: Journal of Clinical Oncology (2018)

e18668 Background: Most studies of racial and ethnic disparities in health care have focused on technical aspects of care, such as diagnostics or therapies while less is known about ethnic differences in accepting a novel medical device. Neulasta Onpro kit eliminates the need for an additional clinic visit for pts receiving chemotherapy. Given the ethnically diverse population in our institution, we investigated acceptance of Onpro kit among cancer pts on chemotherapy. Methods: Single-institution, retrospective review was conducted of pts with predominantly GI tumors who received kit within 1 hour of completion of systemic chemotherapy from Jan 2014 through Jan 2018. Clinic and nursing notes, and pharmacy records were reviewed to identify pts who refused Onpro kit and to discern reasons for refusal. Results: Total 238 orders for kit were voided amongst 68 pts. Median age was 60 years (range 32-87) with 46% of pts ≥ 65. Ethnicities included: Caucasian 41; African American 7; Spanish 3 and Asian 17. Overall, 15/68 pts refused kit (22%). Among them, 13/15 were Asian, 2 Caucasian. Overall, 87% pts were Asian. The reasons for refusal described were: dislike of bulky attachment to their skin, request to place kit on their stomach and not on their arm, having trepidation over unwitnessed administration of drug, fear of reaction, disposal at home, fear of pain and lack of confirmation of proper dose administration and need for MRI. Conclusions: While Onpro kit is an attractive alternative 22% of our pts with voided orders, mainly of Asian backgrounds, declined its application. In 2017, we presented first study in GI malignancies to report the safety and efficacy of same-day administration of manual (subcutaneous) pegfilgrastim. We believe the current study represents the first study to look at important ethnic differences in accepting kit. This study detected ethnic differences and supports importance of cultural factors in determining therapies chosen. Consideration of pts' cultural heritage may facilitate communication between physicians and pts to achieve optimal cancer care. It would be interesting to look at experience or market share of manufacturer in Asian countries. Moreover, translated pt brochures and videos could be very helpful.
Accuracy of self-reported smoking status in adult survivors of childhood cancer: A report from St. Jude Lifetime Cohort study.
Authors: I-Chan Huang, James L. Klosky, Chelsea Young, Sharon Murphy, Deo Kumar Srivastava, Melissa M. Hudson, Leslie L. Robison
Journal: Journal of Clinical Oncology (2017)

10570 Background: Although clinicians often evaluate smoking behavior in cancer survivors via self-report, the validity of this approach is unknown. We validated self-reported smoking status by serum cotinine data in clinically assessed adult survivors of childhood cancer and identified factors contributing to misclassification. Methods: The study sample consists of 287 randomly selected adult survivors of childhood cancers participating in the St. Jude Lifetime Cohort Study and undergoing a risk-based clinical assessment in a survivorship clinic. Self-reported smoking status was classified as never (N = 105), past (N = 111), and current (N = 71) smokers. Age, sex, and race/ethnicity were balanced among the three groups (p’s &gt; 0.05). Blood samples were obtained and serum cotinine levels were quantified by liquid chromatography tandem mass spectrometry. Misclassification was determined by the discrepancies between self-reported smoking status and race/ethnicity-specific serum cotinine thresholds (Benowitz et al. Am J Epidemiol 2009). Multiple logistic regression model was used to identify factors related to misclassification. Results: Of the 287 survivors (mean age = 34 years [range = 19-61]; mean time from diagnosis = 24 years [range = 11-46]), 55.4% were male and 84.0% non-Hispanic white. Cotinine levels consistent with recent active smoking were present in 39.4% compared to 24.7% who self-reported as being a current smoker (X 2 = 14.1; p = 0.0002). Rates of misclassification were 36.9%, 8.4%, and 6.7% in survivors who reported themselves as past, current, and never smokers, respectively. Among self-reported past smokers, 18-30 years of age at survey, male, and current marijuana use increased the risk of misclassification: RR = 3.0 (95%CI = 1.2-7.6), 2.5 (95%CI = 1.1-5.4) and 3.2 (95%CI = 1.1-9.3), respectively. Conclusions: Within a clinical setting, reliance on self-report of smoking status by survivors results in a high misclassification rate. For research, serum cotinine levels should be utilized to assign smoking status. For clinical care and health promotion, clinicians need to be aware of the high rate of misclassification when relying upon self-reported smoking status.
Radiotherapy (RT) to bulky (B) and extralymphatic (E) disease in combination with 6xR-CHOP-14 or R-CHOP-21 in young good-prognosis DLBCL patients: Results of the 2x2 randomized UNFOLDER trial of the DSHNHL/GLA.
Authors: Michael Pfreundschuh, Niels Murawski, Marita Ziepert, Bettina Altmann, Martin H. Dreyling, Peter Borchmann, Stefano Luminari, Mathias Witzens-Harig, Judith Dierlamm, Mathias Haenel, Lorenz Truemper, Bernd Metzner, Eva Lengfelder, Ulrich B. Keller, Christian Ruebe, Christian Berdel, Norbert Schmitz, Gerhard Held, Viola Poeschel
Journal: Journal of Clinical Oncology (2018)

7574 Background: The role of RT to B and E for young patients with good-prognosis DLBCL is ill-defined. Methods: 18-60 year-old patients (aaIPI = 0 with B [≥7.5 cm], aaIPI 1) qualifying for radiotherapy to B or E were randomized to 6xR-CHOP-14 or 6x-R-CHOP-21 followed by RT (39.6 Gy) to B and E sites or observation in a 2x2 factorial design. Primary endpoint was event-free survival. Results: A planned interim analysis of the first 285 patients had revealed a significantly better EFS of patients assigned to RT (p = 0.004) resulting in the pre-defined closing of the non-RT arms. 305 pts (R-CHOP-21: 155; R-CHOP-14: 150) assigned to RT and 162 (R-CHOP-21: 81, R-CHOP-14: 81) assigned to observation were evaluable for this final analysis. There were no relevant differences in protocol adherence and toxicity between the two chemotherapy regimens. EFS, PFS and OS after R-CHOP-14 and R-CHOP-21 were not different. After 66 months median observation 3-year EFS was worse in pts not assigned to RT (68% vs. 84%; p = 0.001), due to a higher rate of PR (11% vs. 2%) triggering additional treatment (mostly RT) as an EFS event. 3-year PFS of pts assigned to RT was not significantly better (89% vs. 81%; p = 0.221) and 3-year OS (93% vs. 93%, p = 0.506) was not different, which was confirmed in a multivariate analysis adjusting for elevated LDH, stage III/IV, B and E involvement (HREFS= 0.5 [95%CI: 0.4-0.8], p = 0.001; HRPFS= 0.7 [0.5-11], p = 0.174; HROS= 1.2 [0.6-2.2], p = 0.674). Results were not different when the analysis was restricted to patients with bulky disease only. Conclusions: There were no differences in outcome between R-CHOP-14 and R-CHOP-21. Patients assigned to observation had a worse EFS because of more events largely due to a higher PR rate triggering additional treatment with no differences in PFS and OS. These results highlight the difficulties in interpreting residual masses in DLBCL without a PET which has been shown to identify (elderly) patients with B who can be spared from radiotherapy without compromising their outcome [Pfreundschuh et al., ASCO 2017, #7506]. Supported by Deutsche Krebshilfe, Amgen and Roche Clinical trial information: NCT00278408.
Association of PD-L1 expression with tumor infiltrating immune cells and mutation burden in the high grade neuroendocrine carcinoma of the lung.
Authors: Hye Sook Kim, Ji-Youn Han
Journal: Journal of Clinical Oncology (2017)

8564 Background: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high grade neuroendocrine carcinoma of the lung and remain among the most fatal malignancies. Programmed death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable for specific immunotherapy. We retrospectively investigated PD-L1 expression in tumor cells (TC) and tumor infiltrating immune cells (IC) and correlated this with mutation burden and clinical outcome. Methods: A total of 192 patients with LCNEC (n = 72) and SCLC (n = 120) were explored. PD-L1 expression was scored by immunohistochemistry in TC and IC. We used the Ion AmpliSeq Comprehensive Cancer Panel to identify mutation in all exons in 409 cancer-related genes. Results: The overall prevalence of PD-L1 expression on TC was 15.1 % (29/192). No significant difference was observed between LCNEC and SCLC (16.7% vs. 14.2%, p = 0.365). Tumor-infiltrating IC and PD-L1 positive immune cells (IC) were observed in 34.4% (66/192) and 31.3% (60/192), respectively. The prevalence of tumor-infiltrating IC and PD-L1 expression on IC were significantly higher in LCNEC compared to SCLC (57.6% vs. 23.3%, p &lt; .001; 45.8% vs. 22.5%, p = .001, respectively). Tumor-infiltrating IC and PD-L1 expression on IC were correlated with higher nonsynonymous mutational load (p = 0.048 and 0.038, respectively). Tumor-infiltrating immune cells (median 11.3 vs. 6.8 months, p = 0.005), and its correlated PD-L1 expression on IC (median 11.3 vs. 7.0 months, p = 0.024) were related with better progression free survival. There was no relevance between biomarker status and overall survival. Conclusions: These findings suggest that the PD-1/PD-L1 pathway is activated in a fraction of HGNEC of lung with correlating higher mutational burden. Further studies are needed to determine the PD-L1 expression and correlated clinical features to refine role of anti-PD1 treatments in these patient population.
P01.065 Tumor treating fields (TTFields) in combination with lomustine (CCNU) in the EF-14 phase 3 clinical study - a safety analysis
Authors: A Kinzel, G Lavy-Shahaf, E Kirson
Journal: Neuro-Oncology (2018)

TTFields are low intensity, intermediate frequency, alternating electric fields. The significant overall and progression-free survival benefit, shown in the EF-14 phase 3 study was seen in all patient-subgroups, independent of e.g. MGMT-promotor methylation-status or age. TTFields were not associated with additional systemic toxicity. At recurrence, patients were allowed to continue TTFields with second-line therapies. Here, we analyzed the safety data of TTFields + lomustine (CCNU) to evaluate safety and feasibility of this combination. Patients in the EF-14 trial received TTFields until second progression, or for 24 months. Change in chemotherapy regimen was allowed after tumor progression. We compared the patients who received lomustine as second-line chemotherapy in combination with TTFields (n=134) to the patients who received lomustine as monotherapy after first progression (n=39). We compared baseline characteristics and the adverse event profile between the groups. Baseline characteristics were well balanced except for less female patients in the lomustine only group (7.7% vs. 22.4%). Median age in the TTFields/lomustine group was 55.5 years (29–83) compared to 50.0 years (19–71) for lomustine alone. The addition of TTFields to lomustine therapy was not associated with any significant increase in systemic adverse events compared to lomustine therapy alone (number of patients with ≥ 1 SAE 30 % vs. 31 %) and the distribution, severity and overall incidence of adverse events were not statistically different in patients in the two treatment groups. The data show that the combination of TTFields and lomustine is safe and feasible. This analysis emphasizes again the strong safety profile of TTFields and the high potential of combining TTFields with other modalities. This data is especially important in light of the recently presented, promising data from a small randomized trial that tested the combination of lomustine + TMZ in newly diagnosed (MGMT promotor-methylated only) glioblastoma patients.