Change In Chemotherapy Regimen Research Articles

Quantitative ultrasound radiomics guided adaptive neoadjuvant chemotherapy in breast cancer: early results from a randomized feasibility study.

In patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC), quantitative ultrasound (QUS) radiomics can predict final responses early within 4 of 16-18 weeks of treatment. The current study was planned to study the feasibility of a QUS-radiomics model-guided adaptive chemotherapy. The phase 2 open-label randomized controlled trial included patients with LABC planned for NAC. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status. All patients were planned for standard anthracycline and taxane-based NAC as decided by their medical oncologist. Patients underwent QUS imaging using a clinical ultrasound device before the initiation of NAC and after the 1st and 4th weeks of treatment. A support vector machine-based radiomics model developed from an earlier cohort of patients was used to predict treatment response at the 4th week of NAC. In the standard arm, patients continued to receive planned chemotherapy with the treating oncologists blinded to results. In the experimental arm, the QUS-based prediction was conveyed to the responsible oncologist, and any changes to the planned chemotherapy for predicted non-responders were made by the responsible oncologist. All patients underwent surgery following NAC, and the final response was evaluated based on histopathological examination. Between June 2018 and July 2021, 60 patients were accrued in the study arm, with 28 patients in each arm available for final analysis. In patients without a change in chemotherapy regimen (53 of 56 patients total), the QUS-radiomics model at week 4 of NAC that was used demonstrated an accuracy of 97%, respectively, in predicting the final treatment response. Seven patients were predicted to be non-responders (observational arm (n=2), experimental arm (n=5)). Three of 5 non-responders in the experimental arm had chemotherapy regimens adapted with an early initiation of taxane therapy or chemotherapy intensification, or early surgery and ended up as responders on final evaluation. The study demonstrates the feasibility of QUS-radiomics adapted guided NAC for patients with breast cancer. The ability of a QUS-based model in the early prediction of treatment response was prospectively validated in the current study. clinicaltrials.gov, ID NCT04050228.

Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases.

Lung metastases are the most common form of distant failure for patients diagnosed with sarcoma with metastasectomy considered for some patients with limited metastatic disease and good performance status. Alternatives to surgery such as stereotactic body radiation therapy (SBRT) can be considered, though data are limited. We present outcomes after SBRT for sarcoma lung metastases. Fifty sarcoma patients with 109 lung metastases were treated with SBRT between 2005 and 2021. Outcomes evaluated included local control (LC), overall survival (OS), and toxicity including lung pneumonitis/fibrosis, chest wall toxicity, dermatitis, brachial plexus, and esophageal toxicity. Systemic therapy receipt before and after SBRT was recorded. SBRT schedules were divided into 3 cohorts: 30 to 34Gy/1fx (n=10 [20%]), 48 to 50Gy/4 to 5fx (n=24[48%]), and 60Gy/5fx (n=16[32%]). With a median follow-up of 19.5 months, 1/3-year LC rates were 96%/88% and 1/3-year OS 77%/50%, respectively. There was no differences between the 3 regimens in terms of LC, OS, or toxicity. Size >4cm was a predictor of worse LC ( P =0.031) and worse OS ( P = 0.039) on univariate analysis. The primary pattern of failure was new metastases (64%) of which the majority were in the contralateral lung (52%). One-year chemotherapy-free survival was 85%. Overall, 76% of patients did not require chemotherapy initiation or change of chemotherapy regimen after lung SBRT. Toxicity was reported in 16% of patients overall, including 25%, 20%, and 14% in the 30 to 34Gy/1fx, 48 to 50Gy/4 to 5fx, and 60Gy/5fx cohorts, respectively. SBRT outcomes for lung metastases from sarcoma demonstrate high rates of LC and are similar with different dose/fractionation regimens. Lung SBRT is associated with prolonged chemotherapy-free survival. Prospective validation of these results is warranted.

Somatostatin Receptor-Directed PET/CT for Therapeutic Decision-Making and Disease Control in Patients Affected With Small Cell Lung Cancer.

Somatostatin receptor (SSTR)-targeted PET/CT is used for patients affected with small cell lung cancer (SCLC), but the clinical impact has not been elucidated yet. We aimed to determine whether SSTR PET/CT can trigger relevant therapeutic management changes in patients with SCLC and whether those modifications achieve disease control and are associated with prolonged survival. One hundred patients with SCLC received SSTR PET/CT. In a retrospective setting, we evaluated the diagnostic performance of PET versus CT and compared therapies before and after PET/CT to determine the impact of molecular imaging on treatment decision. We also determined the rate of disease control after therapeutic modifications and assessed survival in patients with and without changes in the therapeutic regimen. Relative to CT, SSTR PET alone was superior for assessing bone lesions in 19 of 39 instances (49%). Treatment was modified in 59 of 100 (59%) after SSTR PET/CT. Forty of 59 (74.6%) received systemic treatment after hybrid imaging, with the remaining 15 of 59 (25.4%) scheduled for nonsystemic therapy. In the latter group, 13 of 15 (86.7%) received local radiation therapy or active surveillance (2/15 [13.3%]). Individuals scheduled for systemic treatment after imaging received peptide receptor radionuclide therapy (PRRT) in 28 of 44 (63.6%), followed by chemotherapy in 10 of 44 (22.7%), change in chemotherapy regimen in 3 of 44 (6.8%), and initiation of tyrosine kinase inhibitor in the remaining 3 of 44 (6.8%). Among patients with modified treatment, follow-up was available in 53 subjects, and disease control was achieved in 14 of 53 (26.4%). However, neither change to systemic treatment (155 days; hazard ratio, 0.94; 95% confidence interval, 0.53-1.67) nor change to nonsystemic treatment (210 days; hazard ratio, 0.67; 95% confidence interval, 0.34-1.34) led to a prolonged survival when compared with subjects with no change (171 days, P ≥ 0.22, respectively). In patients with SCLC, SSTR-targeted hybrid imaging provides complementary information on the disease status. PET/CT led to management changes in 59% (mainly PRRT), achieving disease control in >26%. The high fraction of patients scheduled for PRRT may lay the foundation for combination strategies to achieve synergistic antitumor effects, for example, by combining PRRT plus recently introduced RNA polymerase II inhibitors.

Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases: Outcomes and Fractionation Schedules

<h3>Purpose/Objective(s)</h3> Lung metastases are the most common site for distant metastases in sarcoma. Mastectomy is associated with improved survival in select patients; however, alternatives such as stereotactic body radiation therapy (SBRT) can be considered for inoperable patients or those who prefer non-surgical management. However, data regarding local control and optimal fractionation are limited. We present outcomes of 3 SBRT regimens, describe patterns of failure and chemotherapy free survival rates after SBRT for sarcoma lung metastases. <h3>Materials/Methods</h3> 50 sarcoma patients were treated with SBRT for 109 lung metastases between 2005 and 2021 with dose regimens including 30-34Gy/1fx (BED₁₀ 120-149.6 Gy), 48Gy-50Gy/4-5fx (BED₁₀ 100-106), and 60Gy/5fx (BED₁₀ 132). At least 6 month follow up was required. Overall survival (OS), local control (LC), chemotherapy free survival, patterns of failure and toxicity were evaluated. <h3>Results</h3> 10 patients received 30-34Gy/1fx, 24 patients received 48-50Gy/4-5fx and 16 patients received 60Gy/5fx. The most common histology for bone sarcomas was osteosarcoma (<i>n</i>=10), and for soft tissue sarcoma was leiomyosarcoma(<i>n</i>=9). At SBRT, median age was 64 years old and 76% of patients had a KPS ≥80. Median tumor size was 1.9 cm (range: 0.3-6.3). With a median follow-up time from SBRT of 19.5 months, 1- and 3-year LC rates were 96% and 88%, with 1- and 3-year OS of 77% and 50%, respectively. There was no statistically significant difference between the 3 regimens in terms of LC, OS or toxicity. No differences in LC or OS were noted based on primary histology; however, a size 4 cm or larger was predictor of worse LC (p=0.031) and worse OS (p= 0.039) on univariate analysis. The primary pattern of failure was new distant metastases occurring in (64%) of patients of which the majority were in the contralateral lung (52%); 4% had lobar failure, 4% had local only failure, and 4% had both local and distant failure. 1-year chemotherapy free survival was 85%. Overall, 76% of patients did not require chemotherapy initiation or change of chemotherapy regimen after lung SBRT (3 remained on same chemotherapy while receiving SBRT). Toxicity was reported in 16% of patients overall, including 25%, 20% and 14 % in the 30-34Gy/1fx, 48-50Gy/4-5fx and 60Gy/5fx cohorts, respectively. Chest wall toxicity was reported in 5 patients overall (1 patient with Grade II in 30-34Gy/1fx cohort, 3 patients, 1 Grade I, II and III in 48-50Gy/4-5fx cohort, and 1 Grade I in 60Gy/5fx cohort), pneumonitis in 3 patients (1 patient with Grade I in 30-34Gy/1fx cohort, 1 patient with Grade II in 48-50Gy/4-5fx cohort, and 1 patient with Grade II in the 60Gy/5fx cohort). <h3>Conclusion</h3> This series of SBRT for sarcoma pulmonary metastases demonstrates that SBRT is effective with comparable outcomes between dose/fractionation regimens. In addition, lung SBRT is associated with an excellent chemotherapy free survival, and can be a potential alternative to surgical resection.

Impact of paclitaxel versus docetaxel on neuropathy in ovarian cancer patients with diabetes.

e17616 Background: Peripheral neuropathy is a common side effect of taxanes, particularly in diabetic patients, which can significantly affect quality of life. The objective of this study was to determine whether there was a difference in the incidence of new or worsening neuropathy between diabetic patients with ovarian cancer who received paclitaxel versus docetaxel as part of their primary therapy. Methods: This retrospective cohort study included ovarian cancer patients with Type I or Type II diabetes at a large academic institution who underwent surgery from 6/2016 to 5/2020 and received neoadjuvant and/or adjuvant chemotherapy. Individual chart review was performed to assess patient characteristics including race, body mass index (BMI), performance status (PS), Charlson Comorbidity Index (CCI), baseline hemoglobin A1c, current diabetic medications. The primary outcome was incidence of new or worsening neuropathy during primary therapy including adjuvant or neoadjuvant chemotherapy. New neuropathy was defined as no neuropathy prior to chemotherapy. Worsening neuropathy was defined as baseline neuropathy that worsened after initiation of chemotherapy. Secondary outcomes included chemotherapy treatment delay, increase of diabetic medications during therapy, and a change of chemotherapy regimen from paclitaxel to docetaxel. Statistical analysis was performed using SPSS v. 26. Results: 32 patients met inclusion criteria. Patient demographics including race, PS, BMI and CCI were similar between patients who received paclitaxel and those who received docetaxel. 24 patients (75%) received paclitaxel and 8 (25%) received docetaxel. The majority (93.8%) of patients had Type II diabetes. Patients who received paclitaxel were more likely to develop new or worsening neuropathy (81% v. 50%; p = 0.028) but less likely to require an increase of diabetic medications (0% v. 50%; p = 0.003) compared with patients receiving docetaxel. During primary therapy, 17% of patients were transitioned from paclitaxel to docetaxel due to treatment-related complications (i.e. neuropathy (50%), allergic reaction (50%)). There was no difference in incidence of treatment delays between the two treatment groups (25% v. 25%; p = 1.0). Conclusions: Patients with ovarian cancer who received paclitaxel were more likely to experience new or worsening neuropathy compared to patients who received docetaxel. There was no difference in treatment delays between the groups, but nearly one-fifth of patients receiving paclitaxel had to be transitioned to docetaxel because of treatment-related complications. Because of fewer side-effects, docetaxel is a reasonable chemotherapy alternative in ovarian cancer patients with diabetes.

Analysis of the Factors in the Low-Risk Invasive Mole Treatment by Methotrexate: A Retrospective Study

The aim of this study is to retrospectively analyze the therapeutic effects of low-risk invasive mole treatment by methotrexate and summarize the high-risk factors which affect the chemotherapy outcome. Collect the clinical data of low-risk invasive mole treatment by methotrexate and analyze the relationship of human chorionic gonadotropin levels and largest tumor sizes with chemotherapy cycle and toxicity in Zhuzhou Central Hospital from 2015 to 2020. In this study, 42 patients of low-risk invasive mole treatment by methotrexate were enrolled in Zhuzhou Central Hospital from 2015 to 2020. All patients are treated by single-agent methotrexate, the remission rates are 80.95 %, the resistance rates are 11.91 % and the relapse rates are 7.14 %. After change of chemotherapy regimen, the cure rates were 100 %. Age, antecedent pregnancy, International Federation of Gynecology and Obstetrics staging and World Health Organization scoring has no significant difference (p=0.785, p=0.412, p= 0.135 and p=0.135, respectively). However, during the pre-treatment, human chorionic gonadotropin levels and largest tumor sizes were significant factors in the study (p=0.017 and p<0.0001). In addition, serum human chorionic gonadotropin levels and largest tumor size were significant risk factors which show impact on the chemotherapy cycles (p=0.023 and p=0.001). In this study, 10 patients have grade 2, 3 patients have grade 3 and 3 patients have grade 4. After careful study, there was no change in chemotherapy plan or death due to chemotherapy toxicity. In this retrospective study, we explained the single-agent methotrexate for the treatment of lowrisk invasive mole, the remission and resistance, and the relapse and chemotherapy toxicity was correlated with serum human chorionic gonadotropin levels and largest tumor size.

B-hCG and H-hCG levels in patients with gestational trophoblastic neoplasia

Objective: Gestational trophoblastic disease is a term that encompasses a spectrum of disorders all arising from the placenta. Human chorionic gonadotropin (hCG) hormone has an essential role in the diagnosis and management of gestational trophoblastic neoplasia. Measuring beta-hCG (B-hCG) levels is the only standard method of monitoring treatment response in patients on chemotherapy. Serial B-hCG levels are also helpful in defining the suitable approach and the dosage of chemotherapeutic drugs. Unfortunately, this marker may not be helpful in some cases. Therefore, the present study was conducted to determine the results of the ratio of B-hCG and hyperglycosylated human chorionic gonadotropin (H-hCG) in patients with gestational trophoblastic neoplasia. Materials and methods: This was a cross-sectional study in 22 patients with gestational trophoblastic neoplasia who were referred to an oncology clinic of an academic hospital of Mashhad University of Medical Sciences in Iran from December 2017 to May 2018. Inclusion criteria were plateau level of B-hCG (during 4 weeks) or persistent low level of hCG. After ruling out other etiologies, H-hCG level was measured and the H-hCG/total hCG ratio was evaluated. If the proportion was more than 20%, active gestational trophoblastic neoplasia was diagnosed, and if it was less than 20%, quiescent gestational trophoblastic neoplasia was diagnosed. In patients with active gestational trophoblastic neoplasia, interventional procedures involved a change in the dose intensity or chemotherapy or proposing a surgery. However, only serial follow-up was recommended in patients with quiescent gestational trophoblastic neoplasia. Then, the patients were followed during the therapy and the condition of patients was followed and recorded. Results: The mean age of patients was 31.36 ± 8.01 years. Hydatidiform mole was the most common diagnosis, accounting for approximately 64% (14) of patients. A total of 81% of patients were undergoing chemotherapy. The interval time between the onset of chemotherapy until plateau or persistent low level of hCG was 11.26 ± 4.03 weeks. The mean B-hCG level was 36.6 mIU/mL and the mean H-hCG/total hCG ratio was 6.24%. This proportion was less than 20% in 82% of patients. Among these patients, 14 patients (77.8%) had spontaneously normalized levels of B-hCG during a 6-month follow-up. Two cases underwent chemotherapy due to increased B-hCG. Other patients are still under follow-up without disease progression. Among 4 patients with a H-hCG/total hCG ratio &gt;20%, hysterectomy was recommended to one patient duo to multiparity and the fact that the tumor was localized in the uterus. In the other patients, an increase in the dose of methotrexate or a change of chemotherapy regimen was performed, which caused a decrease in B-hCG level to normal. All patients are still under follow-up without disease progression. Conclusion: The data in this study suggests the use of H-hCG as a tumor marker in patients with persistent low level of B-hCG, which is useful to distinguish between quiescence gestational trophoblastic neoplasia, which does not need treatment, from active gestational trophoblastic neoplasia. However, further studies with larger sample size are needed to confirm and generalize the above findings. Keywords: gestational trophoblastic

Cancer Incidence and Chemotherapy Tolerance in Patients with Sickle Cell Disease

With improved understanding and treatment of sickle cell disease (SCD), patients are more likely to live into the sixth decade. Survival into older adulthood may be associated with a concomitant risk of malignancy in this population. Past studies have yielded conflicting data regarding the incidence of cancer in SCD. Some studies show an increased risk of hematologic malignancies or solid tumors, while others demonstrate a decreased propensity for cancers in patients with SCD. Delays in treatment and dose reductions can adversely affect response and survival outcomes, but little is known about the ability of SCD patients to tolerate treatment for various malignancies. We studied the incidence of cancer and tolerance of chemotherapy over a 10-year-period at the University of Illinois at Chicago in a retrospective chart review. Our study included 1484 SCD patients of all ages seen at our institution from September 30, 2010 to April 29, 2020. The patient records were queried for common malignancies using ICD-9 and ICD-10 codes, including colorectal, lung, breast, prostate, renal, and cervical cancer as well as lymphoma, leukemia, and multiple myeloma. These cases were verified by manual chart review (Figure 1A). The incidence of cancer was compared to an African American (AA) control cohort of 22,260 patients matched for age, sex, and follow-up time. For patients who received chemotherapy, details on regimen and tolerability were obtained. Baseline variables were defined as the median of all available values three years prior to treatment. Dose limiting toxicities (DLT) were defined as any reason for which an expected dose could not be administered. Of the 1484 SCD patients, 48 (3.2%) had a cancer diagnosis according to ICD codes. Among the AA control population, 1282/22260 (5.8%) had cancer according to ICD codes. The incidence of common malignancies was significantly decreased in the SCD population (OR 0.55, p&amp;lt;0.001, 95% CI 0.40 to 0.73). Of the 48 SCD cancer cases, we were able to confirm 19 (39.6%) by manual chart review and 16 of these patients were diagnosed during the study period. Characteristics of the 16 SCD cancer patients are summarized in Table 1 and distribution of cancer types is shown in Figure 1B. Eight (50%) of these patients were known to receive chemotherapy, and treatment details are shown in Table 2. First-line treatment was not given in 2 (25%) cases due to comorbidities such as SCD, poor functional status, toxicity, age, and renal insufficiency. Grade 3 or 4 toxicities took place in 5 (62.5%) patients, including anemia, neutropenia, leukopenia, thrombocytopenia, dehydration, nausea and or vomiting, and hemorrhagic cystitis. Six (75%) patients had a vaso-occlusive crisis (VOC) and 1 (12.5%) had an acute chest syndrome episode during therapy. DLT in 4 (50%) patients included nephrotoxicity, infection, pain, and hepatotoxicity. Four (50%) patients did not receive all scheduled cycles for reasons including concern for cerebrovascular accident (CVA), fatigue, anorexia, dehydration, VOC, infection, and progression of disease. Two (25%) patients required change in chemotherapy regimen due to toxicity. Our study raises several questions regarding both the incidence and treatment of cancer in SCD. There was a significantly lower incidence of cancer among SCD patients compared to AA controls. Mechanisms by which SCD patients may be protected from cancer are unknown, but should be explored in future studies. Patients who received chemotherapy in our study experienced significant toxicities, delays, and dose reductions. Such issues were often SCD-related or due to other typical hematologic toxicities. Although the goal for treating SCD cancer patients may be with therapies that result in outcomes similar to the general population, our data suggests that this is difficult with routine protocols. Increased monitoring and a multimodal approach to symptom control may increase treatment tolerability and ensure adequate dose delivery. Evidence of poor chemotherapy tolerance in SCD patients highlights the need for further and larger studies to determine treatment strategies for this population. Disclosures Saraf: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer, Global Blood Therapeutics, Novartis: Research Funding. Gordeuk:Novartis: Consultancy; CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding.

The role of imaging in early detection of patients at risk for neuropathy during primary chemotherapy for ovarian carcinoma.

e18071 Background: Neuropathy is a common adverse event requiring dose reduction or regimen change in patients receiving platinum-taxane chemotherapy for ovarian cancer. Our aim was to determine whether specific biomarkers, such as skeletal muscle, visceral and subcutaneous fat cross-sectional areas, measured using computerized tomography (CT), were associated with the development of neuropathy. Analytic Morphomics, a semi-automated image analysis method, has been used to predict oncologic outcomes with immunotherapy and to identify patients at higher risk for postoperative complications from major cancer surgeries. We hypothesized that patients who required dose reductions or regimen changes would have CT imaging findings that distinguished them from their counterparts who did not require dose reduction or regimen change. Methods: All patients at our institution diagnosed with high-grade ovarian carcinoma between January 1, 2014 and December 31, 2018 were identified retrospectively. Analytic Morphomics was used to extract measures of body composition from CT images at the level of the third lumbar vertebra. Demographic and clinical characteristics were abstracted from the electronic medical record. We analyzed several binary outcomes (neuropathy, delay in chemotherapy, or dose reduction by cycle 1, 3 or 6) and used unpaired, two-tailed t-tests to compare means between each outcome group at each timepoint. Results: Of 156 patients screened for the study, 138 patients were included and had pre-treatment CT scans available and completed six cycles of platinum-taxane chemotherapy. Patients who developed neuropathy in any of the six cycles, or had a change in their chemotherapy regimen by cycle six, had higher mean visceral fat area than those who did not develop neuropathy. This finding was statistically significant throughout three cycles (p = 0.023) and six cycles (p = 0.030). Conclusions: Increased visceral fat on CT imaging was significantly associated with a higher incidence of neuropathy and change in chemotherapy regimen in patients undergoing primary platinum-taxane chemotherapy for ovarian carcinoma. Weight and BMI did not have a significant association with development of neuropathy, dose reduction, or treatment delay. Further study is needed to determine if dose reductions or regimen changes due to neuropathy can be better predicted using morphomics.

SAT-337 ACUTE KIDNEY INJURY IN PATIENTS WITH SOLID ORGAN AND HAEMATOLOGICAL MALIGNANCIES: A SINGLE CENTRE EXPERIENCE

Acute kidney injury(AKI) is common in patients with malignancies, both solid organ and haematological malignancies. The aim of this study was to look at the incidence of acute kidney injury and its clinical correlates in patients with haematological and solid organ malignancies receiving chemotherapy. Population: All patients, more than 18 years of age receiving outpatient chemotherapy for solid organ and haematological malignancies at our hospital from Jan 2016 to Dec 2016. Data collected using MOSAIQ( Local Oncology Database) and Hospital Database. Patients were retrospectively followed up during the course of the year for acute kidney injury, which was identified using Creatinine measurements recorded in the lab database. Incidence of acute kidney injury was computed and its causes and clinical correlates were analysed using univariate analysis and multivariate analysis. AKI was defined using rifle criteria, serum Creatinine part of the definition. Injury was defined as Creatinine rise upto 50% above baseline. Results: 592 patients were included in the study. Most common malignancies were bowel cancer followed by breast. Acute kidney injury during the one year course of chemotherapy was seen in 158 patients (27.24%). Pre-renal acute kidney injury was seen in 82 patients (51.8%) and intrinsic renal in 20 patients (12.65%) and post renal cause in 35 patients (22.15%). In 21 patients (13.31%) of study population, cause of acute kidney injury was not identified. When we subclassified each of the causes, sepsis was the most common cause of acute kidney injury seen in 31 patients (19.6%), followed by hypovolumia in 24 patients (15.1%). Bilateral hydronephrosis occurred in 23 patients (14.5%). Interestingly there were 13 patients where the acute kidney injury was attributed to drugs. 5 patients had NSAIDS exposure and 8 patients had chemotherapeutic drug causing AKI. The chemotherapy drugs were Lenalidomide, Methotrexate, Ibrutinib, Pamidronate, Gemcitabine, Vemurafinib and Crizotinib. Patients with acute kidney injury attributed to above drugs had either a dose reduction or change in chemotherapy regimen. None of the patients had a renal biopsy to confirm drug induced pathology. However all of the patients had resolution of acute kidney after stopping the drug or changing the regimen. Also of note, only one patient with pamidronate induced acute kidney injury was referred to nephrology service. Looking at individual cancer types, 5 out of 10 patients (50%) with RCC developed acute kidney injury followed by lymphoma ( n=22, 43%) prostate (n=17, 41%) and myeloma(n=15, 39%). Although bowel and breast cancer were the two most common cancers, proportion of AKI in this group was (n=41,29%) and( n=6, 7%) respectively. Factors associated with acute kidney injury, higher ECOG score, diabetes and hypertension were associated with higher risk of developing acute kidney injury. Contrast to other published papers, having metastatic disease was not associated with higher risk of acute kidney injury. Acute kidney injury is associated with increased mortality. We observed the same trend in our study. Without adjusting for confounding factors, mortality in the acute kidney group at 6, 12 and 18 months was 15%, 31% and 46% compared to Non AKI group which was 5%, 26% and 43%. AKI is common in patients with malignancies and its associated with mortality.

ACTR-01. SAFETY ANALYSES OF TUMOR TREATING FIELDS IN COMBINATION WITH LOMUSTINE IN THE EF14 PHASE 3 CLINICAL STUDY

INTRODUCTION: Tumor Treating Fields (TTFields) are low intensity (1-3V/cm), intermediate frequency (100–300 KHz) alternating electrical fields approved for glioblastoma (GBM). In the EF-14 phase 3 study, TTFields showed a significant overall and progression-free survival benefit for patients with newly diagnosed GBM in combination with Temozolomide (TMZ). TTFields were not associated with systemic toxicity. At recurrence, patients continued TTFields with second line therapies. We analyzed the safety and feasibility of TTFields + lomustine (CCNU) combination. Patients in the EF-14 trial received TTFields until second progression, or for 24 months. Change in chemotherapy regimen was allowed in both groups after tumor progression. We compared patients who received lomustine as second-line chemotherapy in combination with TTFields (n=134) to patients who received lomustine as monotherapy after first progression (n=39). We compared baseline characteristics and the adverse event profile between the two groups. Baseline characteristics were well balanced; there were 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) versus 50.0 years (19–71) for lomustine alone. The addition of TTFields to lomustine therapy was not associated with any significant increase in rates of 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. CONCLUSION: 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 therapy 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 plus TMZ in newly diagnosed (MGMT promotor-methylated only) GBM patients.

Abstract CT108: Tumor treating fields (TTFields) in combination with Lomustine (CCNU) in the EF-14 phase III clinical study: A safety analysis

Abstract Introduction: TTFields are low intensity (1-3V/cm), intermediate frequency (100-300 KHz) alternating electrical fields for the treatment of solid tumors. In the EF-14 phase 3 study, TTFields showed a significant overall and progression-free survival benefit for patients with newly diagnosed glioblastoma (GBM), in combination with Temozolomide (TMZ) (OS from randomization 20.9 vs. 16.0 months, p-value&amp;lt;0.001). The OS and PFS benefit of TTFields was seen in all patient subgroups, and was independent of MGMT promotor methylation-status, age, performance status and gender. 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 the safety and feasibility of this combination. Methods: Patients in the EF-14 trial received TTFields until second progression, or for 24 months. Change in chemotherapy regimen was allowed in both groups 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 two groups. Results: Baseline characteristics were well balanced between both groups 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 rates of systemic adverse events compared to lomustine therapy alone (number of patients with &amp;gt; 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. Discussion: The data show that the combination of TTFields and lomustine is a safe and feasible combination. This analysis emphasizes again the strong safety profile of TTFields and the high potential of combining TTFields with other therapy 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) GBM patients. Citation Format: Adrian Kinzel, Gitit Lavy-Shahaf, Eilon D Kirson. Tumor treating fields (TTFields) in combination with Lomustine (CCNU) in the EF-14 phase III clinical study: A safety analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT108.

A Rules-Based Algorithm to Prioritize Poor Prognosis Cancer Patients in Need of Advance Care Planning.

Accurate understanding of the prognosis of an advanced cancer patient can lead to decreased aggressive care at the end of life and earlier hospice enrollment. Our goal was to determine the association between high-risk clinical events identified by a simple, rules-based algorithm and decreased overall survival, to target poor prognosis cancer patients who would urgently benefit from advanced care planning. A retrospective analysis was performed on outpatient oncology patients with an index visit from April 1, 2015, through June 30, 2015. We examined a three-month window for "high-risk events," defined as (1) change in chemotherapy, (2) emergency department (ED) visit, and (3) hospitalization. Patients were followed until January 31, 2017. A total of 219 patients receiving palliative chemotherapy at the University of Chicago Medicine with a prognosis of ≤12 months were included. The main outcome was overall survival, and each "high-risk event" was treated as a time-varying covariate in a Cox proportional hazards regression model to calculate a hazard ratio (HR) of death. A change in chemotherapy regimen, ED visit, hospitalization, and at least one high-risk event occurred in 54% (118/219), 10% (22/219), 26% (57/219), and 67% (146/219) of patients, respectively. The adjusted HR of death for patients with a high-risk event was 1.72 (95% confidence interval [CI] 1.19-2.46, p = 0.003), with hospitalization reaching significance (HR 2.74, 95% CI 1.84-4.09, p < 0.001). The rules-based algorithm identified those with the greatest risk of death among a poor prognosis patient group. Implementation of this algorithm in the electronic health record can identify patients with increased urgency to address goals of care.

P3.01-082 Surgical Rebiopsy in Advanced Non-Small Cell Lung Cancer Resistant to Previous Chemotherapy

To optimize the personalized medicine for advanced non-small cell lung cancer (NSCLC), sufficient tumor tissue is mandatory to analyze molecular and genetic profile. The demand for repeat biopsy in NSCLC is increasing, it is more difficult to obtain specimen after initial treatment. The aim of this study was to evaluate the impact of surgical rebiopsy in advanced NSCLC. From Jan 2014 to Mar 2017, 146 consecutive patients underwent surgical rebiopsy for NSCLC which was resistant to prior chemotherapy. Their medical records were reviewed retrospectively. There were 60 male and 86 female patients with mean age of 57 years (range 30-83). Adenocarcinoma was most common histologic type (n=142, 93%). Among them, 107 patients represent EGFR mutation before chemotherapy, deletion in exon 19 (n=73) was most frequently observed. Before surgical rebiopsy, 121 patients (83%) were treated with EGFR-TKIs. The mean number of change in chemotherapy regimen was 2 (range 1-6) and 24% of patients underwent more than 3 different chemotherapy before rebiopsy. The median time between initial treatment and rebiopsy was 17.4 months (IQR 9-25). Surgical rebiopsy was possible in all cases. One hundred and seven patients (73%) underwent pleura biopsy, 22 underwent lung resection and 12 patients underwent both pleural and lung resection. Most procedure underwent video-assisted thoracic surgery (n=136, 93%), 10 patients required mini-thoracotomy. Median postoperative hospital stay was 4 days (IQR, 3-6) and the 30-day mortality was 2.7%. All specimens were confirmed as NSCLC and adequate for mutational and genetic analysis except 2 patients. One patient was failed to mutational analysis, other patients was failed to genetic sequencing due to low tumor volume. After surgery, 129 patients can resume chemotherapy. Of those, 85 patients were enrolled clinical trial or treated with new target agent. Thirty nine patients were treated with cytotoxic chemotherapy and 5 patients continued with prior target agent. Surgical rebiopsy can detect changes in cancer characteristics and may be used in therapeutic decision making in advanced NSCLC resistant to previous treatment.

A rules-based algorithm to identify patients who would benefit from re-addressing advance care planning.

4 Background: Advance care planning (ACP) should be initiated early and readdressed often for cancer patients. We hypothesize that a rules-based algorithm can predict decreased overall survival, and can be used to target patients who would benefit from readdressing ACP. Methods: We performed a retrospective analysis of 219 patients receiving palliative chemotherapy with leukemia, cholangiocarcinoma, esophageal, gastric, pancreatic, lung or urothelial cancer at the University of Chicago Medicine. Patients were included if they had an index outpatient oncology visit from April 1, 2015 through June 30, 2015. We examined a three-month window from the index visit for a “high-risk event,” defined as: 1. change in chemotherapy 2. emergency department visit 3. hospitalization. Patients were followed from index visit until date of death or last clinical encounter as of January 31, 2017. Each “high-risk event” was treated as a time-varying covariate in a Cox proportional hazards regression model to calculate a hazard ratio of death compared to those without an event. Results: Sixty-seven percent of patients (146/219) experienced at least one high-risk event. A change in chemotherapy regimen, an ED visit, and a hospitalization occurred in 54% (118/219), 10% (22/219) and 26% (57/219) of patients respectively. The hazard ratio of death for patients with at least one high-risk event when compared to those without was 1.72 (95% CI: 1.19-2.46, p=0.003), when adjusted for age, gender, race, marital status, disease type, ECOG, and Charlson score. Inpatient admission independently reached significant for hazard of death. (HR 2.74: 95% CI: 1.84-4.09, p&lt;0.001). Conclusions: The rules-based algorithm identified patients with a greater risk of death. Implementation of this algorithm in the electronic medical record can identify patients with increased urgency to readdress goals of care. [Table: see text]

A rules-based algorithm to identify patients who would benefit from re-addressing advanced care planning.

e21510 Background: Advance care planning (ACP) should be initiated early and readdressed often for cancer patients. We hypothesize that a rules-based algorithm based on occurrence of high-risk events can predict decreased overall survival, and can be used to target patients who would benefit from readdressing ACP. Methods: We performed a retrospective analysis of 221 patients receiving palliative chemotherapy with a diagnosis of leukemia, cholangiocarcinoma, esophageal, gastric, pancreatic, lung or urothelial cancer at the University of Chicago Medicine. Patients were included if they had an index outpatient oncology visit from April 1, 2015 through June 30, 2015. Starting at the date of index visit, we examined a three-month window for a “high-risk event,” defined as: 1. change in chemotherapy 2. emergency department visit 3. hospitalization. Patients were followed from index visit until date of death or last clinical encounter as of January 31, 2017. Each “high-risk event” was treated as a time-varying covariate in a Cox proportional hazards regression model to calculate a hazard ratio of death compared to those without an event. Results: Sixty-six percent of patients (146/221) experienced at least one high-risk event over the 3 month time frame. A change in chemotherapy regimen, an ED visit, and a hospitalization occurred in 53% (118/221), 10% (22/221) and 26% (57/221) of patients respectively. The hazard ratio of death for patients with at least one high-risk event when compared to those without was 1.86 (95% CI: 1.26-2.74, p = 0.002), when adjusted for age, gender, and race. Inpatient admission had the highest hazard of death among the high-risk events (HR 2.52: 95% CI: 1.69-3.76, p &lt; 0.001). Conclusions: The rules-based algorithm identified patients with a greater risk of death. Implementation of this algorithm in the electronic medical record can identify patients with increased urgency to readdress goals of care.

Etoposide-Actinomycin as Salvage Regimen for the Treatment of Nonmetastatic and Low-Risk Metastatic Gestational Trophoblastic Neoplasia: Experience at the Philippine General Hospital.

Single-agent chemotherapy has been the standard of treatment for nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia (GTN). However, it is estimated that approximately 12% to 32% of patients given single-agent therapy will require a change of chemotherapy regimen because of drug resistance and/or intolerable toxicity. The Section of Trophoblastic Diseases of the Philippine General Hospital started using the combination of etoposide-actinomycin (EA) as salvage chemotherapy in the early 2000s. This study was carried out to describe the local experience with this salvage chemotherapy. This is a retrospective descriptive study aimed to analyze the efficacy and safety of the EA regimen as salvage treatment for the management of nonmetastatic and low-risk metastatic GTN. Records of the Section of Trophoblastic Diseases of the Philippine General Hospital from January 1, 2002 to June 30, 2014 were reviewed to identify all patients who had a diagnosis of nonmetastatic and metastatic low-risk GTN. Primary remission rate and toxicity profile of all patients who received the EA regimen as salvage treatment were determined. During the study period, a total of 67 cycles of the EA regimen were administered to 15 patients as salvage chemotherapy. Patients received a median of 4 cycles of EA, attaining normal serum beta human chorionic gonadotropin after 2 to 3 cycles. Thirteen of the 15 patients achieved complete remission with the EA regimen, giving a remission rate of 87%. The major toxicity that the patients experienced was myelosuppression. Grade 1/2 anemia was addressed by blood transfusion. Grade 3 neutropenia/myelosuppression was addressed by the administration of granulocyte colony-stimulating factor. Alopecia was seen in all of the patients. One patient experienced dermatitis with accompanying myelosuppression. The EA regimen was efficacious and well tolerated for the treatment of refractory nonmetastatic and low- risk metastatic GTN.

Change in Management Based on Pathologic Second Opinion Among Bladder Cancer Patients Presenting to a Comprehensive Cancer Center: Implications for Clinical Practice

To evaluate the incidence and degree of change from a pathologic second opinion of bladder biopsies at a Comprehensive Cancer Center that were initially performed at referring community hospitals. The secondary objective was to determine the impact the potential changes would have on a patient's treatment. Dedicated genitourinary pathologists reviewed 1191 transurethral biopsies of the bladder and/or prostatic urethra from 2008 to 2013. Major and minor treatment changes were defined as altering recommendations for cystectomy, systemic chemotherapy, or primary cancer diagnosis, and alterations in intravesical regimens, respectively. There were 326/1191 patients (27.4%) with a pathologic change on second opinion: grade (62/1191, 5.2%), stage (115/1191, 9.7%), muscle in the specimen (29/1191, 2.4%), presence or absence of carcinoma in situ (34/1191, 2.9%). Outside pathology did not address the presence or absence of lymphovascular invasion in 620/759 (81.7%) of invasive cases (≥cT1), of which 35/620 (5.6%) had lymphovascular invasion. There were 212 mixed, variant, or nonurothelial histologies detected in 199/1191 (16.7%) patients, with 114/212 (53.7%) resulting in reclassification by our pathologists. Potential treatment alterations accounted for 182/1191 (15.3%) of cases, with 141/1191 (11.8%) imparting major changes. There were 82/1191 (6.8%) changes in recommendation for a radical cystectomy, 38/1191 (3.2%) had a complete change in primary tumor type, and 21/1191 (1.8%) for change in chemotherapy regimen. The amount and degree of pathologic changes and its potential impact on treatment emphasize the importance of bladder cancer patients having their histology reviewed by genitourinary-dedicated pathologists. In our cohort, 15.3% of patients could see a treatment alteration, with 11.8% being a major change.

Role of baseline echocardiography prior to initiation of anthracycline-based chemotherapy in breast cancer patients.

BackgroundAnthracycline adjuvant therapy has taken a particular role in the treatment of early stage breast cancer with an associated decrease in rates of both relapse and death. Their success however has been limited by their myelosuppression and their well-established risk of cardiac dysfunction. Guidelines have emerged that would limit the maximum lifetime dose of anthracyclines and make a baseline assessment and periodic monitoring of cardiac function part of the routine practice, which could be cumbersome, and may condemn the patient to an unwarranted modification of his/her regimen. Our study aimed at assessing the incidence of abnormal baseline echocardiography in asymptomatic women with breast cancer prior to anthracycline therapy and establishing risk criteria associated with abnormal echocardiograms at baseline.Methods220 Patients seen at AUBMC (American University of Beirut Medical Center) who had non- metastatic breast cancer, and had an echocardiography performed before starting anthracycline chemotherapy were chosen. Data about demographic characteristics, tumor characteristics, baseline echocardiography results, and change in clinical decision was collected. Patients with suboptimal (less than 50%) ejection fraction (EF) on baseline echocardiography were analyzed for the prevalence of cardiac risk factors. Results were compared to those among the overall study group using Fisher’s Exact test. A p- value of = < 0.05 was used as reference for statistical significance.ResultsAll 220 of our patients had received a baseline echo prior to initiation of anthracycline therapy. 6.7% of these patients had already some abnormality in wall motion but only 2.7% had a suboptimal ejection fraction. 1.3% had a change in chemotherapy regimen based on ejection fraction. The patients with depressed EF had higher rates of CAD (coronary artery disease), diabetes, hypertension and dyslipidemia than the overall study group but without statistical significance.ConclusionsOur study, as well as the previous contingent studies raise the question about routine echocardiography prior to anthracycline therapy and might eventually lead to a modification of current practice guidelines.

Concomitant urothelial cancer and renal tuberculosis.

We report a case of coexisting urothelial cancer and renal tuberculosis in the same kidney. The patient is a 72-year-old female with a remote history of treated pulmonary tuberculosis who presented with haematuria, initial investigation of which elucidated no definitive cause. Almost 1 year later, a diagnosis of metastatic urinary tract cancer was made. The patient received chemotherapy for advanced collecting duct type renal cell carcinoma, based on histological features of renal biopsy. Subsequent confirmatory immunostains however led to a revised diagnosis of urothelial cancer, necessitating a change in chemotherapy regimen. A diagnosis of ipsilateral renal tuberculosis was made based on TB-PCR testing of renal biopsy tissue and anti-TB therapy was coadministered with chemotherapy. The patient died 9 months after diagnosis of metastatic urothelial cancer.