tbuckley/cabot-search huggingface dataset:
Evaluating the impact of telephonic nurse care management during high toxicity chemotherapy treatment.
Authors: Craig A Hunter, Andrew C Krueger, Omar A Soliman, Angela S Inman, Erika R Glenn, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2019)

6623 Background: Care management is aimed at improving quality and cost of cancer care. To measure this we evaluated inpatient (IP) and emergency room (ER) admissions and costs of chemotherapy patients receiving versus not receiving telephonic nurse care management. Methods: 1,609 patients were studied over a 35 month period, of which 802 enrolled in a voluntary holistic telephonic nurse care management program. Patients were identified based on having been prescribed or initiating treatment with a high toxicity chemotherapy agent within the previous 60 days, following which notification was received from an oncology pathways intermediary. Nurse care managers engaged patients one or more times per month based on patient need, educating on side effects, pain management, where to seek care, and general well-being. IP and ER were measured during the 14 days following chemotherapy administration (Risk-Period) and compared to a baseline of all remaining patient claims history, excluding 28 days following chemotherapy administration (14 day Risk Period and 14 day washout period). Results: IP rates per 1,000 Risk Period Days for managed patients decreased during the 14 days following chemotherapy by 44% as compared to their baseline (3.02 v 5.39, p≤0.001), while non-managed patients increased by 29% (2.33 v 1.81, p=0.003). ER rates per 1,000 Risk Period Days were not significantly different for managed patients (2.72 v 2.35, p=0.188) and significantly increased by 117% for non-managed patients (2.34 v 1.08, p≤0.001). Baseline utilization for managed patients was more than twice the rate of non-managed patients, suggesting that a greater need for support may influence voluntary participation in care management. Conclusions: Telephonic nurse care management meaningfully reduced IP and ER admissions and their associated costs. [Table: see text]
Adoptive transfer of tumor-infiltrating lymphocytes in patients with sarcomas, ovarian, and pancreatic cancers.
Authors: Rodabe Navroze Amaria, Chantale Bernatchez, Marie-Andree Forget, Cara L. Haymaker, Anthony Paul Conley, J. Andrew Livingston, Gauri Rajani Varadhachary, Milind M. Javle, Anirban Maitra, Ching-Wei David Tzeng, Emily Hinchcliff, Virginia Bayer, Yvonne Gasior, Tyler Hilton, Joseph Celestino, Kelly M Rangel, Ying Yuan, Karen H. Lu, Patrick Hwu, Amir A. Jazaeri
Journal: Journal of Clinical Oncology (2019)

TPS2650 Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has a long history of efficacy in metastatic melanoma, and is being increasingly considered across other solid tumors. Preclinical data generated at MD Anderson Cancer Center has demonstrated the ability to grow TIL from a variety of tumor types including various types of sarcomas, ovarian and pancreas cancers. We are testing the efficacy of TIL across multiple tumor types using two different manufacturing protocols. Methods: We are conducting two ongoing investigator initiated basket TIL therapy trials. The first (NCT03449108) includes cohorts with poorly differentiated soft tissue and bone sarcomas, osteosarcoma, and platinum resistant ovarian cancer. The TIL product used in this trial is an investigational cell product (LN-145, Iovance Biotherapeutics, Inc.). The second trial (NCT03610490) includes cohorts of osteosarcoma, platinum resistant ovarian cancer, and pancreatic cancer (who have progressed on, or received maximal benefit from, front-line therapy). For this trial, TIL are manufactured at MD Anderson Cancer Center using a protocol that includes the use of urelumab (an agonistic anti-CD137 antibody) combined with T cell receptor activation during TIL expansion. In both trials eligible subjects undergo tumor harvest using a surgical excisional biopsy of the tumor for TIL manufacturing, receive a modified cyclophosphamide and fludarabaine lymphodepletion regimen and up to six doses of IL-2 (600,000 IU/kg) following TIL infusion. No intervening therapy is allowed between tumor harvest and initiation of lymphodepletion. The primary endpoint for each cohort is ORR as assessed by investigators using RECIST 1.1 criteria. The Simon’s two stage design is used to monitor the efficacy of each cohort independently. In the first stage, 10 patients will be treated per cohort. If there is no confirmed response in these 10 evaluable patients, the cohort will be terminated. If the cohort moves forward to Stage II, an additional 8 patients will be treated leading to a total of 18 patients. Three or more responders out of 18 treated patients for the cohort will be considered clinically relevant to justify further investigation. Enrollment is ongoing in all cohorts in both trials. An accrual update will be provided at the annual meeting. Clinical trial information: NCT03449108, NCT03610490.
Are elderly breast cancer patients offered appropriate therapy i.e. surgery, chemotherapy, radiation, and endocrine therapy, in a rural population?
Authors: Alexander Johnson, Christian Agbisit, Kristin Delfino, Kathy Robinson, Meghna R. Desai
Journal: Journal of Clinical Oncology (2019)

e12053 Background: The NCI SEER data demonstrated that age adjusted incidence rate of geriatric breast cancer is 427.5 per 100,000. Mortality rates for breast cancer have improved over the last 20 years,but the risk of breast cancer death has decreased 3 fold more rapidly in younger vs. geriatric population. Comorbid illnesses are more prevalent in elderly &amp; therapy offered is often less aggressive. The objective of this study was examine practice patterns in a rural geriatric breast cancer population. The patients were divided into groups with life expectancies (LE) &gt; 10 years or not. Analysis was also performed in groups based on age ranges. Methods: An institutional database of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 or older at the time of diagnosis was reviewed in an IRB approved fashion. Data was collected on age at diagnosis, LE, and the rates of chemotherapy, surgery, radiation therapy, multidisciplinary discussion, clinical trials, Adjuvant Online!, &amp; endocrine therapy offered. LE data was divided into patients with greater than 10 years of life expectancy or not at the time of diagnosis. A separate analysis examined the rates of the above in age ranges of 65-70, 71-80, and 81 plus. Variations in significance were identified using Fishers Exact Test. Results: 44 patients (16.4%) had a LE at diagnosis of &lt; 10 years. Surgery was offered in n=262 patients (97.4%). Radiation therapy was offered in n=170 patients (64.9%). Endocrine therapy was offered in n= 221 patients (83.1%). Chemotherapy was offered in n= 72 patients (27.2%). In the greater than or less than 10 year LE group, statistically significant variations were noted in the rates of radiation (p=0.0047) &amp; chemotherapy (p=0.0067) treatments offered to patients based on their life expectancy. When patients were grouped by age range, statistically significant variations were noted in the rates of radiation treatment (p=0.0221), endocrine treatment (p=0.032), chemotherapy (p≤0.0001), &amp; participation in clinical trials (p=0.0218). Conclusions: Our study identified statistically significant differences in the rates of radiation &amp; chemotherapy offered to patients based on their life expectancy. Statistically significant differences in rates of radiation, endocrine therapy, chemotherapy, and participation in clinical trials were observed based on the age ranges of patients. No differences were noted in the rates of surgery offered, use of Adjuvant Online, and multidisciplinary discussion based on LE &amp; age range.
Diagnosis of lung cancer by canine olfactory detection in urine and breath samples.
Authors: Charlotte Feil, Thorsten Stein, Andreas Forster, Irene Schmidtmann, Thomas Riemann-Seibert, Martin Berger, Robert Owen, Carl Christoph Schimanski
Journal: Journal of Clinical Oncology (2019)

e13067 Background: Lung cancer is the leading oncological cause of death in western countries. The WHO estimated 2.09 million newly diagnosed lung cancer patients in 2018 worldwide. Although early detection is crucial for patients outcome, no surveillance tools exist. Dogs have a highly sensitive olfactory system which is already used in several ways, such as drug and ketone detection. The aim of the study was to evaluate the capability of a classically conditioned domestic dog to accurately distinguish samples of lung cancer patients of all tumor stages in urine and breath from healthy controls. Methods: This monocentric clinical trial was an original study and approved by the local ethics committee. After conditioning a domestic dog with samples of 186 patients (36 cancer patients and 150 control patients), further 246 patients aged between 45 and 80 entered into the study: 41 patients with a histologically proven lung cancer comprising all different stages and 205 control samples of healthy individuals with no cancer history. Two urine and two breath samples were collected of each patient and immediately shock frozen at -80°C. Urine and breath samples were separately exposed to the dog in a randomized, double-blinded manner, resulting in a specific conditioned reaction indicating the cancer sample. Results: The dog correctly predicted cancer in 36 of 41 urine samples, corresponding to a sensitivity of 87.8% and a specificity of 97.6%. Concerning the breath samples, the dog correctly predicted cancer in 32 of 41 samples, corresponding to a sensitivity of 78% and a specificity of 95.6%. Combining both techniques, the dog correctly identified 40 of 41 cancer samples, leading to an overall sensitivity of 97.6%. The specificity is not evaluable. Conclusions: Urine and breath carry volatile organic compounds indicating cancer growth, as previously reported. Canine olfactory detection of lung cancer is a simple tool to detect lung cancer non-invasively. Further identification of target compounds for technical translation of this approach is under way, with the potential for the development of a bionic electronic nose.
TP53 mutations in EGFR mt+ NSCLC IV as a predictive factor for ORR, PFS, and OS irrespective of T790M.
Authors: Julia Roeper, Anne Christina Lueers, Markus Falk, Markus Tiemann, Fabian Otto-Sobotka, Frank Griesinger
Journal: Journal of Clinical Oncology (2019)

e20679 Background: The impact of TP53 mutations in EGFR mt+ pts on PFS and OS is controversial, and different classifications of TP53 mt+ with respect to functional and potential predictive impact have been published. Therefore, we retrospectively analyzed the impact of TP53 aberrations on ORR, PFS and OS in a cohort of EGFR mt+ NSCLC IV pts (UICC 7) using different classifications of TP53 mutations. Methods: 75 EGFR mt+ NSCLC IV pts were analyzed for TP53 co-mutations. TP53 mt+ were classified according to Poeta et al. into (1) disruptive vs. non-disruptive, according to structural prediction and biophysical characteristics into (2) pathogenic vs. non-pathogenic and finally into (3) exon 8 vs. non-exon 8 mutations according to Crino et al.. The endpoints ORR according to Recist 1.1, PFS and OS were calculated by Kaplan Meier. Results: 69 of the 75 EGFR mt+ pts (92%) had a common mutation in EGFR E19/21. In 59/75 pts (79%) material was sufficient for successful TP53 analysis. TP53 mt+ were found in 29/59 pts (49%), 16/59 (27%) had a TP53 disruptive mt+, 13/59 (22%) a TP53 non-disruptive mt+ and 30/59 a TP53 WT configuration. Using the structural/biophysical classification, 7/59 (12%) had a TP53 non-pathogenic and 22/59 (37%) a TP53 pathogenic mt+. Of the 29 mutated pts, 6 had a TP53 Exon 8 mt+. Median PFS on 1 st line TKI was 12 vs. 18 months for non-disruptive/disruptive mt+ vs. WT (p &lt; 0.004), 11 vs. 17 months for pathogenic vs. non-pathogenic/WT (p &lt; 0.0001), and 7 vs. 12 vs. 18 months for exon 8 vs. non-exon 8 vs. WT (p &lt; 0.006). Median OS was 24 vs. 42 months in non-disruptive/disruptive mt+ vs. WT (p &lt; 0.0009), 23 vs. 42 months in pathogenic vs. non-pathogenic/WT (p &lt; 0.001) and 12 vs. 28 months for TP53 exon 8 vs. non-exon 8 mt+ (p &lt; 0.024). Additionally ORR was significantly impacted by TP53 mt+. In rebiopsy samples on acquired resistance, no new TP53 mutations were observed and there were no correlations of TP53 mutations with clinical factors and the EGFR mt+ type including T790M. Conclusions: TP53 seems to be a frequent co-mutation in EGFR mt+ NSCLC and has a strong impact on all clinical endpoints on TKI therapy. These data might have an impact on the management and follow up of pts with TP53 mt+. Furthermore, there is an urgent need for further therapeutic approaches in this patient group.
Comparison of HER2 overexpression with total <i>Her2</i> mutation on resistance of EGFR-targeted therapy in <i>Ras</i> wild-type mCRC patients.
Authors: Wenju Chang, Wenbai Huang, Yijiao Chen, Li Ren, Ye Wei, Jianmin Xu
Journal: Journal of Clinical Oncology (2019)

3594 Background: Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harboring wild-type Ras, however, only partial patients respond to cetuximab treatment. The effect of human epidermal growth factor receptor 2 (HER2) protein overexpression and Her2 gene mutant on the efficacy of cetuximab treatment was not well elucidated in patients with Ras wild-type unresectable mCRC. Methods: From June 2008 to December 2014, we identified 216 patients with Ras wild-type unresectable liver-limited mCRC base on our previous study (ClinicalTrials: NCT01564810.), whose Her2 gene mutation was analyzed by next-generation sequencing for single nucleotide polymorphism (SNP) of Her2 gene and HER2 protein overexpression was determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Results: Of these 216 patients, 103 were received cetuximab plus chemotherapy (cetuxima group) and 113 were received chemotherapy alone (chemotherapy group). The total rate of HER2 overexpression was 8.8%, including 9.7% in cetuximab group and 7.9% in chemotherapy group. HER2 overexpression caused impaired survival compared with HER2 non-overexpression patients in cetuxima group, with a median progression-free survival (PFS) of 4 months (95% CI 2.482-5.518) versus 10 months (95% CI 8.963-11.037; P&lt; 0.0001), and a median overall survival (OS) of 15 months (95% CI 7.5-22.2) versus 36 months (95% CI 31.4-40.5) ( P&lt; 0.0001). While, HER2 overexpression had no effect on treatment efficacy in chemotherapy group, when compared with HER2 non-overexpression paitents, with a median PFS of 5 months (95% CI 2.228-7.772) versus 5 months (95% CI 4.004-5.996; P= 0.615), and a median OS of 21 months (95% CI 6.975-35.025) versus 21 months (95% CI 17.772-24.228; P= 0.629). Meanwhile, we observed 25.5% of total Her2 mutant (24.2% in cetuximab group and 26.5% in cetuximab group), among of them 5 patients are HER2 overexpression. Total Her2 mutation has no impact on survival compared with Her2 wild-type ones in neither cetuximab group nor chemotherapy group. In further bioinformatics analysis is underdoing, and which subgroup or type of Her2 mutant potential affect cetuximab treatment need confirm. Conclusions: We show HER2 overexpression rather than total Her2 mutant contribute to resistance of cetuximab treatment in patients with mCRC harboring wild-type Ras. Next, the subgroup mutant in total Her2 mutant needs further analysis to confirm their roles in survival after cetuximab treatment.
Combined treatment of patients with bone metastases from various cancers with nivolumab plus denosumab: A retrospective study.
Authors: Yukinori Ozaki, Yuji Miura, Taro Yamanaka, Kohji Takemura, Rika Kizawa, Momoko Takahashi, Jun Masuda, Chihiro Kondoh, Yuko Tanabe, Toshimi Takano
Journal: Journal of Clinical Oncology (2019)

e14153 Background: Monoclonal antibodies against the programmed cell death protein-1 (PD-1), e.g., nivolumab, have been shown to exhibit antitumor immunity and improve survival in patients with various cancers. Recently, it was reported that bone metastases are unlikely to respond to immunotherapy, while other reports have suggested that synergistic antitumor effect can be obtained by administration of denosumab in combination with PD-1 blockade using nivolumab. However, there are still very limited data on the efficacy and effects on the prognosis of nivolumab administered in combination with denosumab in patients with bone metastases. Methods: We reviewed the medical records and pharmacy database of patients who had received nivolumab plus denosumab treatment from April 2011 to March 2018 at our institution, in order to analyze the prognosis of patients with bone metastases from various cancers. The primary objective was to compare the progression-free survival between patients with and without bone metastases. The impact of combined nivolumab plus denosumab therapy was evaluated as an exploratory endpoint. Results: We extracted 201 patients who had received denosumab for bone metastasis and 45 patents who had received immune checkpoint inhibitor. We analyzed the data of 39 patients who had received nivolumab treatment; of these 39 patients, 10 had additionally also received denosumab for the treatment of bone metastases. The median age of the patients was 65 years (range 41-87); the primary disease was renal cell carcinoma in 17 patients, gastric cancer in 9 patients, melanoma in 6 patients, non-small cell lung cancer in 4 patients, and head and neck cancer in 3 patients. The median progression-free survival following treatment with nivolumab was 2.1 months in the group with bone metastases and 3.5 months in the group without bone metastases (log-rank test; p = 0.0779); the 6-month progression-free survival rate was 26.7% (95% CI: 21.6-69.2) in the patients with bone metastases and 39.3% (95% CI: 10.4-53.3) in those without bone metastases. Concurrent administration of denosumab, age, and the primary disease had no influence on the progression-free survival rate. Conclusions: This retrospective analysis revealed a trend towards lower immune responses in patients with bone metastases, even when nivolumab is administered in combination with denosumab. Immunotherapy for bone metastasis needs to be further explored.
Activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601).
Authors: Yoland Catherine Antill, Peey Sei Kok, Kristy Robledo, Elizabeth Barnes, Michael Friedlander, Sally E. Baron-Hay, Catherine M. Shannon, Jermaine Coward, Philip James Beale, Geraldine Goss, Tarek Meniawy, Sonia Yip, Deborah Smith, Amanda B. Spurdle, Michelle Parry, John Andrews, Marzena Kelly, Martin R. Stockler, Linda R. Mileshkin
Journal: Journal of Clinical Oncology (2019)

5501 Background: Deficient DNA mismatch repair (dMMR) occurs in approximately 15% of AEC and is associated with a high tumour mutation burden. Expression of PD-1 and PD-L1 has been reported in up to 90% of ECs, including those with proficient DNA mismatch repair (pMMR). We report here preliminary results of PHAEDRA, a single-arm phase 2 trial designed to determine the activity of single-agent durvalumab, an antibody to PD-L1, in 2 cohorts of women with AEC. Methods: Participants (pts) had pMMR AEC progressing after 1-3 lines of chemotherapy, or dMMR AEC progressing after 0-3 lines of chemotherapy, and were treated with durvalumab 1500mg IV Q4W. The primary endpoint was objective tumour response (OTR = complete response [CR] or partial response [PR] by iRECIST). Secondary endpoints included disease control at 16 weeks (DC16w = CR, PR, or stable disease at 16 weeks [SD16w]), immune-related adverse events (irAEs), PD-L1, germline mutations and MLH1 methylation. Other secondary endpoints include: OTR and DC by RECIST1.1, other AE, PFS, OS &amp; quality of life will be reported later. Results: 71 pts with AEC were recruited from Feb 2017 to Sep 2018: 35 dMMR and 36 pMMR. Median follow-up were 8.3 vs 14.8 months in dMMR vs pMMR pts. Median age: 67 (range 36-81); ECOG PS: 0-1 in 68, and 2 in 3. Pathology: endometrioid in 94% and 58%; serous in 0% and 31%; grade: high in 42% and 83% (dMMR and pMMR respectively). Durvalumab was the 1 st , 2 nd and subsequent line of non-hormonal therapy in 15, 14, and 6 pts with dMMR and 0, 21, and 15 pts with pMMR. Among dMMR pts, the OTR rate was 40% (14/35, 95% CI 26-56), with 4 CR and 10 PR; 7 others had SD 16w for a DC16w rate of 60% (21/35, 95% CI 44-74). OTR rate was 40% as 1 st line, 43% as 2 nd line, and 33% as subsequent line treatment. Among pMMR pts, the OTR rate was 1/36 (3%, 95% CI 1-14) with 1 PR; 6 others had SD16w for a DC16w rate of 19% (7/36; 95% CI 10-35). IrAEs occurred in 14 pts: hyperthyroidism in 6, hypothyroidism in 6, pneumonitis in 1 and hepatitis in 1. Conclusions: Durvalumab monotherapy showed promising activity and safety in AEC with dMMR regardless of prior lines of chemotherapy, but there was limited evidence of activity in AEC with pMMR. Clinical trial information: ACTRN12617000106336.
Valuing innovations in cancer treatment.
Authors: Henu Zhao, Bryan Tysinger, Dana P Goldman
Journal: Journal of Clinical Oncology (2019)

e18176 Background: Established in 2004 by voter referendum, the California Institute for Regenerative Medicine funds stem-cell research aimed at reducing the burden of diseases, including cancer. Incidence for certain cancer has been reduced by half in the last decades. To better understand the social benefit of medical innovation, we estimate the potential value of interventions to reduce the incidence of selected cancers. Methods: We use the Future Elderly Model (FEM) to simulate scenarios calculating the national and California disease burden of breast, colorectal, lung, and prostate cancer and the societal value of reducing incidence of these cancers by 10% and 50%, respectively. FEM is a well-validated microsimulation model of Americans aged 51 and older that projects future health and economic outcomes for individuals. Starting with a nationally representative sample from the Health and Retirement Study, we estimate two-year transitions between chronic diseases, functional status, and economic outcomes. We predict EQ-5D scores and quality-adjusted life-years (QALY) based on the outcomes and models using Medical Expenditure Panel Survey data. We then aggregate individual results to generate outcomes at the societal level. Results: Social values are measured by QALY, with each unit valued at $150,000. Yearly discount rate for future QALY is 3%. Estimated gains in aggregate social value from 2018 to 2050 are presented below. For the selected cancers, the disease burden of the selected cancers through 2050 ranges from $1.3 trillion to $3 trillion for the U. S. population &gt;50. QALY gains from a 50% reduction in incidence are estimated at $0.5 trillion to $1.4 trillion, while gains from a 10% reduction are $110 billion to $252 billion. Conclusions: A small incidence reduction can result in large returns. There is a lot of potential for innovation in cancer. [Table: see text]