tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherapy in muscle invasive bladder cancer: Real world data on safety and outcome.
Authors: Sree Vamsee Chetana Panthula, Arun Philip, Pavithran Keechilat, Wesley Mannirathil Jose
Journal: Journal of Clinical Oncology (2020)

e17036 Background: The standard treatment for Muscle Invasive bladder cancer (MIBC),Radical Cystectomy and Neoadjuvant chemotherapy (NACT) has shown to improve survival. Data from Indian population is scarce, and we sought to explore the efficacy, tolerability and factors affecting the outcome of Neoadjuvant chemotherapy in our population. Methods: This was a Retrospective Observational study conducted at a tertiary care centre. Patients of MIBC treated between 2008 and 2019 were included in the analysis. The NACT consisted of Gemcitabine + Cisplatin (GC) or Gemcitabine + Carboplatin (GCa). The prognostic significance of the various clinico-laboratory parameters was assessed by the log rank test. The survival analysis was done by the Kaplan Meier method. Results: Total of 40 patients received NACT from 2008-2019. The median age of study group was 62 years. Male to Female ratio was 5:1. Out of 40 patients, 26 were treated with GC and the remaining 14 received GCa. Majority (80%) patients were administered either 3 or 4 cycles of NACT. Among 18 patients who demonstrated good radiological response after NACT completion, 13 had received Cisplatin. After NACT, 32 (80%) underwent Radical Cystectomy and 3 were treated with CTRT. The remaining 5 did not receive definitive treatment. Pathological complete response (PCR) was achieved in 10 out of 32 patients (31%). Out of 10 patients with PCR, 9 belonged to Cisplatin group and only 1 in Carboplatin group. In patients with PCR, 80% remained progression free at last follow up. Grade 3/4 toxicities were minimal. However, achieving a pathological CR did not translate into significant survival benefit in our study (p value 0.10). Median follow up time and overall survival for the cohort was 29.5 and 54 months respectively. Conclusions: Gemcitabine/Cisplatin as NACT resulted in superior radiological response, PCR, PFS and OS when compared to Gemcitabine/Carboplatin in MIBC. This regimen is well tolerated and we advocate for further prospective studies with GC in this setting. [Table: see text]
Prevalence of childhood growth hormone deficiency in survivors of pediatric intracranial germ cell tumors.
Authors: Diana Lone, Karim Thomas Sadak, Bradley S Miller, Michelle Roesler, Jenny N Poynter
Journal: Journal of Clinical Oncology (2020)

e22526 Background: Survival rates for childhood cancer continue to rise, and there are now greater than 420,000 survivors in the United States. However, high cure rates come at the cost of short and long-term treatment-related toxicities. Endocrine disorders are among the most common late effects and are associated with poor health outcomes and lower quality of life. Survivors of pediatric intracranial germ cell tumors (iGCTs) are at high risk for endocrine disorders, particularly for growth hormone deficiency (GHD), due to their exposures to cranial radiation, chemotherapy, and brain surgery. To date, no long-term follow-up studies have explored the late effects experienced by survivors of iGCTs. Methods: Study participants were enrolled in the Germ Cell Tumor Epidemiology Study, which is a case-parent triad study conducted using the resources of the Children’s Oncology Group’s Childhood Cancer Research Network. Eligibility criteria included diagnosis with a germ cell tumor in any location at age 0-19 years in the years 2008-2015. The study population included 233 cases with a diagnosis of iGCT. We are currently following the cohort to evaluate outcomes and late effects of treatment, including medical record review to extract data on treatment characteristics and hormone deficiencies. This interim analysis includes chart review for 57 iGCT cases. Results: Of the 57 cases reviewed, there was a male predominance (73.7%) with the highest prevalence in non-Hispanic whites (80.4%). Cases of iGCTs can be subdivided into two main histologic subtypes, germinomas (36 cases) and non-germinomatous GCTs (NGGCT, 21 cases). The median age at diagnosis was 14.6 years for the germinomas and 10.5 years for NGGCTs. Data on growth hormone deficiency (GHD) was available for 42 of the 57 cases with a median follow-up of 7.4 years. Twenty-eight of the 42 cases (66.7%) had GHD; 19 in the germinoma group and 9 in the NGGCT group (p = 0.47). 17 of those with GHD were males (p = 0.10). There was no significant difference in prevalence of GHD by age of tumor diagnosis (p = 0.20). Conclusions: Survivors of iGCTs are at high risk for growth hormone deficiency. Identifying specific risk factors for developing GHD amongst these survivors can enhance the current guidelines for screening and management.
Mutational distinction between adenocarcinoma <i>in situ</i>, minimally invasive adenocarcinoma and invasive adenocarcinoma in lung cancer patients with multiple tumors.
Authors: Jixian Liu, Yingmei Li, Yuancai Xie, Xinyu Luan, Xuxing Peng, Tianhao Mu, Shifu Chen, Da Wu
Journal: Journal of Clinical Oncology (2020)

e21089 Background: Lung adenocarcinoma is the most popular lung cancer type, and it can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) based on histology. The mutational similarities and differences have not been discussed in these subtypes. Methods: Targeted deep sequencing was performed on 31 lung adenocarcinomas with matched blood samples from 15 patients with multiple tumors. We compared mutations among each subtype. Results: The 31 tumors consisted of 10 AIS, 6 MIA and 15 IA subtypes; the median mutation number in each type was 1, 1 and 3 respectively. Eleven, six and fifty-three mutations were identified in AIS, MIA, and IA respectively. Among all the 67 mutations, only EGFR_p.L858R was found in all three types; BRAF_p.K601E was found in AIS and IA. Conclusions: AIS, MIA and IA harbor distinct mutational signatures, except for several popular driver mutations, suggesting their distinct origin and evolution path.
Olaparib (O) in patients (pts) with pancreatic cancer with BRCA1/2 inactivating mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.
Authors: Eugene R Ahn, Elizabeth Garrett-Mayer, Susan Halabi, Pam K. Mangat, Carmen Julia Calfa, Ajjai Shivaram Alva, Vijay S. Suhag, Omid Hamid, Efrat Dotan, Eddy Shih-Hsin Yang, Olatunji B. Alese, Kathleen J Yost, Alissa S. Marr, Martin Clive Palmer, Forrest L. Thompson, Andrew Lawrence Rygiel, Sarah T. Anderson, Samiha Islam, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2020)

4637 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pancreatic cancer pts with germline or somatic BRCA1/2 inactivating mutations treated with O are reported. Methods: Eligible pts had advanced pancreatic cancer, no standard treatment (tx) options available, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received O tablets or capsules dosed at 300 mg (n=27) or 400 mg (n=3), respectively, orally twice daily until disease progression. Simon 2-stage design tested the null disease control (DC) (objective response (OR) or stable disease at 16+ weeks (wks) (SD16+) according to RECIST) rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS), and safety. Results: Thirty pts with BRCA1/2 inactivating mutations were enrolled from Nov 2016 to Aug 2019; 20 were previously treated with platinum based therapy. Two were not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One partial response (PR) and 7 SD16+ were observed for DC and OR rates of 31% (90% CI: 18% - 40%) and 4% (95% CI: 0% - 18%), respectively. Seven pts had at least one grade 3 AE or SAE at least possibly related to O including anemia, diarrhea, fever, elevated liver enzymes, enterocolitis, increased bilirubin, and oral mucositis. Conclusions: Monotherapy O showed anti-tumor activity in heavily pre-treated pts with pancreatic cancer with germline (5/12 pts with OR or SD16+) or somatic (3/16 pts with OR or SD16+) BRCA1/2 inactivating mutations extending findings of recent studies of O in pts with advanced pancreatic cancer. Clinical trial information: NCT02693535 . [Table: see text]
Incidence of chemotherapy-induced nausea and vomiting in 2008
Authors: I. Martin, V. Montheil, S. Ropert, J. Alexandre, F. Goldwasser, J. P. Durand
Journal: Journal of Clinical Oncology (2009)

e20660 Background: The authors determined the incidence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) among new patients (pts) receiving chemotherapy with modern antiemetic prophylaxis in 2008. Methods: A prospective observational study of adult cancer pts receiving, for the first time, moderately or highly emetogenic chemotherapy (MEC or HEC) was performed. Study participants were called on day 2 and day 8, after first and second cycle, to evaluate acute and delayed emesis according a 10-item questionnaire. All patients received, before and after their chemotherapy, the optimal antiemetic prophylaxis according to the 2006 Update of ASCO Guideline for Antiemetics. Results: 131 consecutive pts were enrolled between January and June 2008. At cycle 1, on 124 assessable pts for acute emesis: 68 pts received MEC and 18, HEC. 5.6% developed acute vomiting (5.9% for MEC and 5.6% for HEC) and 33.1%, acute nausea (39.7% for MEC and 44.4% for HEC). At cycle 1, on 101 assessable pts for delayed emesis: 5% experienced delayed vomiting (5.1% for MEC and 6.3% for HEC) and 17.8%, delayed nausea (18.6% for MEC and 31.3% for HEC). At cycle 2, on 121 assessable pts for acute emesis: 62 pts received MEC and 18, HEC. 8.3% developed acute vomiting (6.5% for MEC and 16.3% for HEC) and 31.4%, acute nausea (35.5% for MEC and 44.4% for HEC). At cycle 2, on 96 assessable pts for delayed emesis: 5.2% experienced delayed vomiting (3.3% for MEC and 9.1% for HEC) and 19.8%, delayed nausea (23% for MEC and 27.3% for HEC). Conclusions: Though the application of the last antiemetic recommendations, CINV, especially nausea, remained a substantial toxicity for patients receiving chemotherapy, pointing out the need for improved therapeutic intervention. [Table: see text]
The role of surgery in stage I small-cell lung cancer: A national VA database analysis.
Authors: Ibrahim Azar, Adam Austin, Seongho Kim, Hyejeong Jang, Amit Chopra, Syed Arzoo Mehdi, Hirva Mamdani
Journal: Journal of Clinical Oncology (2020)

e21109 Background: Historically, limited stage Small Cell Lung Cancer (SCLC) has been treated with concurrent chemoradiation (CRT). While current NCCN guidelines recommend consideration of lobectomy in node-negative cT1-T2 SCLC, real world data regarding the role of surgery in very limited SCLC is lacking. To our knowledge, only one retrospective study has evaluated the role of surgery in stage I SCLC. Methods: Data from the National VA Cancer Cube were compiled. A total of 1,028 patients with pathologically confirmed Stage I SCLC were studied. Only 661 patients that either received surgery or CRT were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Subset analysis was performed based on the location of the tumor in the upper vs lower lobe as delineated by ICD-10 codes C34.1 and C34.3. Results: Four-hundred and forty-two patients received concurrent CRT; while 219 underwent treatment that contained surgery (92 surgery only, 84 surgery/chemo, 39 surgery/chemo/radiation and 4 surgery/radiation). The median OS for the surgery-inclusive treatment was 3.87 years (95% CI 3.25-4.60) while median OS for the CRT cohort was 2.43 years (95% CI 2.15-2.72). HR of death for surgery-inclusive treatment when compared to CRT was 0.65 (95% CI 0.54-0.79; p &lt; 0.001). Subset analysis based on the location of the tumor in upper lobe and lower lobe showed improved survival with surgery as compared to CRT regardless of the location. HR for upper lobe was 0.61 (95% CI 0.48-0.78; p &lt; 0.001) and lower lobe 0.60 (95% CI 0.41-0.87; p = 0.007). Multivariable regression analysis accounting for age and ECOG-PS shows a HR 0.60 (95% CI 0.42-0.85; p = 0.004) favoring surgery. Conclusions: Surgery was used in less than a third of patients with stage I SCLC who received treatment. Surgery-inclusive multimodality treatment was associated with a longer overall survival as compared to chemoradiation, independent of age, performance status or tumor location. Our study supports a more expansive role for surgery in stage I SCLC.
Treatment of thoracolumbar fractures by unilateral pedicle screw fixation plus short segment pedicle screw through para-vertebral muscles
Authors: Lei Han, Renfu Quan, Dawei Bi, Gang Zu, Hui Wang
Journal: BMJ (2014)

A total of 33 non–neurological symptoms patients with thoracolumbar fractures underwent unilateral pedicle screw fixation plus short segment pedicle screw through para–vertebral muscles. Preoperative computed tomography (CT) scan showed one side pedicle was complete. The average follow–up period was 22 (12–40) months. There was no internal fixation failure. The posterior paraspinal approach for unstable thoracolumbar fractures, retaining posterior ligament complex and fixation by unilateral pedicle screw fixation through the pedicle of fractured vertebra, is both safe and effective for thoracolumbar fractures.


Key words: 
Surgical procedures, operative; Spinal fractures
Polymorphism of IL-4 receptor gene in patients with childhood wheezing
Authors: Yong-sheng Xu, Li Song, Li-heng Dang, Shu-xiang Lin
Journal: BMJ (2009)

The study eonsisted of 128 children with wheezing and 82 healthy subjects. PCR-RFLP was used to detect IL-4R gene 150V and Q576R. There were difference in I50 and V50, Q576 and 11576 allele frequency and genotypic frequency between childhood wheezing patients and normal children. Genotype 150/I50 was correlated with the susceptibility for wheezing (P=0.015, OR=0.439, 95% CI=0. 223 - 0. 826). The susceptibility for wheezing was related to the combination of I50/I50 and Q576/R576. Results of this study suggest that childhood wheezing is closely related to genetic factors, and children who carry predisposing genes may suffer from frequent wheezing and subsequent asthma.

Key words: 
Receptor; interleukin-4;  Genetic predisposition to disease
Role for Biochemical Assays and Kayser-Fleischer Rings in Diagnosis of Wilson’s Disease
Authors: Yi Dong, Rou-Min Wang, Guo-Min Yang, Hao Yu, Wan-Qing Xu, Juan-Juan Xie, Yue Zhang, Yu-Chao Chen, Wang Ni, Zhi-Ying Wu
Journal: Clinical Gastroenterology and Hepatology (2020)
Neoadjuvant chemotherapy (NACT) and HER2 double inhibition including biosimilar trastuzumab (ONTRUZANT) for HER2-positive early breast cancer (EBC): Population-based real world data from the Danish Breast Cancer Group (DBCG).
Authors: Michael Andersson, Maj-Britt Jensen
Journal: Journal of Clinical Oncology (2020)

577 Background: Increasingly, HER2-positive early breast cancer (EBC) is treated by NACT combined with trastuzumab and pertuzumab followed by surgery. Ontruzant is registered as a biosimilar trastuzumab based on the totality of evidence including a randomized phase III study of NACT+Herceptin versus NACT+Ontruzant demonstrating similar pCR-rates (Pivot et al. J Clin Oncol 2018;36:968). However, no data exist for the efficacy of the combination of NACT with pertuzumab+Ontruzant (p+O). This investigator-initiated study was conducted to assess real world efficacy in HER2-positive EBC patients treated with NACT+p+O based on data from DBCG. DBCG has since 1977 provided guidelines for treatment of breast cancer and collected data from Danish hospital departments of surgery, pathology, and oncology prospectively on NACT, date and type of surgery and patho-anatomic findings. Methods: From the DBCG database, information was extracted for consecutive patients with unilateral early HER2-positive breast cancer registered to have received NACT+p+O from September 1, 2018 to August 31, 2019. pCR was defined as absence of residual invasive tumor in the breast and axillary lymph nodes (ypT0/Tis ypN0(i-)). Results: 215 patients received NACT+p+O. Median age was 54.8 years (range 24-81). NACT used, in combination with concurrent p+O, was cyclophosphamide+epirubicin followed by paclitaxel (62% on 6 cycles and 35% on 8 cycles) or other chemotherapy followed by paclitaxel (3%). Overall, 56% of patients achieved a pCR (Table). 68% of node-positive patients before receiving NACT+p+O had tumor-free axillary nodes after completing NACT+p+O. Conclusions: Real-world data from a nationwide population based study demonstrated a pCR-rate with NACT+p+O comparable to that seen in clinical studies with NACT+p+Herceptin (Chen et al. BMC Cancer 2019;19:973). pCR-rate was highly dependent on estrogen receptor (ER)-status and malignancy grade but not on clinical nodal status and tumor size. 68% of patients with cN+ converted to ypN0(i-). [Table: see text]
Association between complete response and survival in advanced melanoma treated with talimogene laherparepvec (T-VEC) plus ipilimumab (ipi).
Authors: Jason Alan Chesney, Igor Puzanov, Frances A. Collichio, Mohammed M. Milhem, Axel Hauschild, Min Yi, Sumita Bhatta, Rubina Ismail, Claus Garbe, Parminder Singh, Janice M. Mehnert
Journal: Journal of Clinical Oncology (2020)

10029 Background: This is the first randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor for advanced melanoma. At the 3-year (yr) follow-up, the combination (combo) of T-VEC and ipi demonstrated durable and statistically superior objective response rate (ORR) over ipi alone (36.7% vs. 16.0%; odds ratio, 3.0; 95% Cl, 1.6–6.0; P = 0.002). Complete response (CR) rate was 21.4% with the combo and 6.0% with ipi. Median overall survival (OS) was not reached in either arm. In this post hoc analysis, we utilized the 3-yr landmark data to explore the relationship between CR and OS in the combo arm. Methods: Pts with unresectable, stage IIIB-IV melanoma were randomized 1:1 to receive combo or ipi alone. T-VEC was administered intratumorally on day 1 of week (wk) 1 at 10 6 plaque-forming units (PFU)/mL followed by subsequent doses at 10 8 PFU/mL on day 1 of wk 4, and every 2 wks thereafter. Ipi (3 mg/kg) was given every 3 wks starting on day 1 of wk 6 for up to 4 doses. Response was assessed by investigators per immune-related response criteria every 12 wks until disease progression. The primary endpoint was ORR; key secondary endpoints were OS, progression-free survival, and safety. Results: 198 pts were randomized (98 to combo; 100 to ipi). As of February 25, 2019, the median follow-up time was 40.0 mos (range: 0.2–63.7) for the combo arm. Among 98 pts who received combo, 21 (21.4%) had a best overall response of CR including 8 who converted from an initial partial response (PR), 15 (15.3%) had PR, 19 (19.4%) had stable disease, 30 (30.6%) had progressive disease, and 13 (13.2%) were unevaluable. Of 21 pts achieving CR, 17 (81%) had ECOG status of 0, 16 (76.2%) had stage IIIB-IVM1a disease, and 16 (76.2%) had no visceral metastases. Median duration of CR was not reached (range: 5.4[+]–58.2[+] mos); 19 of 21 CRs lasted more than 6 months. The baseline tumor burden was lower in pts with CR than in those with non-CR. Median OS was not reached in pts with CR (range: 25.1[+]–63.7[+] mos) and was 47.6 mos (range: 0.2[+]– 63.7[+] mos) in pts with non-CR (Log-rank P = 0.0005). The Kaplan–Meier estimated 3-year OS rate was 100.0% for patients with CR and 52.3% for those with non-CR. Conclusions: CR rate was higher with T-VEC plus ipi than with ipi alone in pts with advanced melanoma (21.4% vs. 6.0%). In the combo arm, CR was associated with prolonged OS, and pts with CR tended to have better ECOG performance status, earlier-stage disease, and lower baseline tumor burden, as compared with those with non-CR. Clinical trial information: NCT01740297.
Using novel biomarkers to predict chemotherapy-induced cardiovascular toxicity in patients with breast cancer.
Authors: Krithika Krishnarao, DeLisa Fairweather, Katelyn Bruno, Erika Douglass, Xochiquetzal Geiger, Winston Tan, Lauren Cornell, Mohamad Yamani
Journal: Journal of Clinical Oncology (2020)

e13002 Background: Despite improvement in survival in breast cancer patients from advanced therapies, rates of chemotherapy-induced cardiotoxicity manifesting as a decline in left ventricular ejection fraction (LVEF) have offset some of these benefits in patients receiving anthracycline-based chemotherapy followed by trastuzumab. Results suggesting clinical biomarkers predict cardiotoxicity are inconsistent. Recently, expression of angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) has shown to play a role in breast tumor growth. We sought to evaluate whether the presence of ATR1 and ET1 in breast cancer tissue using immunohistochemistry (IHC) and qRT-PCR can predict chemotherapy-induced cardiotoxicity. Methods: We hypothesized that elevated expression of ATR1 and ET1 in tumor tissue is associated with chemotherapy-induced cardiotoxicity (LVEF &lt; 50%) compared to tissue from controls. Preliminarily, 34 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were retrieved for analysis. IHC and qRT-PCR for expression of ATR1 and ET1 was performed on all specimens. Results: We found that ET1 expression was significantly increased in patients with an LVEF &lt; 50%. In addition, we noted the lower the LVEF, the higher the ET1 expression (p = 0.03). We also found patients with a change in LVEF of greater than 10% had more ET1 expression compared to those without a change in LVEF (p = 0.05). We did not find a significant relationship between ATR1 and LVEF. Conclusions: Increased ET1 expression in breast tumor tissue may predict cardiotoxicity. Our findings may aid in future research using novel biomarkers to predict breast cancer patients at risk for developing chemotherapy-induced cardiotoxicity. In addition, targeted therapies to these biomarkers may potentially help prevent the development of cardiotoxicity.