Initiation Of Chemotherapy Treatment Research Articles

Osmotic Demyelinating Syndrome Secondary to Breast Cancer Chemotherapy: a Case Report (P10-5.024)

<h3>Objective:</h3> To report a case of osmotic demyelinating syndrome (ODS) secondary to chemotherapy for breast cancer. <h3>Background:</h3> ODS comprises both central pontine demyelination and extrapontine myelinolysis. This condition accounts for 0.4% to 0.56% of neurological admissions to tertiary referral hospitals and 0.06% of medical admissions. Although rapid correction of hyponatremia is the most common cause, other etiologies such as alcohol consumption, chronic renal failure, and organ transplantation are also reported. Chemotherapy can be an infrequent cause of this condition. Here we describe a case of ODS in a normonatremic patient in treatment with trastuzumab, pertuzumab, and docetaxel. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> A 71-year-old female with a history of breast cancer, with lung and brain metastases, is seen in the emergency room due to a decline in her functionality over the past three months, following the initiation of chemotherapy treatment with trastuzumab, pertuzumab and docetaxel. On neurological examination, she exhibited cognitive failures and a non-fluent aphasia without focal neurologic signs. In addition, right-sided focal seizures successfully managed with levetiracetam. On neuroimaging, there were signs of pontine myelinolysis and a reduction in the size of previous brain metastatic lesions. After discontinuing chemotherapy, the patient’s speech and gait significantly improved. <h3>Conclusions:</h3> ODS could be associated with combination chemotherapy treatment in the setting of a normonatremic patient. In 2014, Sungjae Lee and colleagues reported a similar case in a patient with colon cancer who received 5-fluorouracil, oxaliplatin, and leucovorin chemotherapy. In another study published by Cortes and colleagues, the development of osmotic demyelinating syndrome when using a combination of trastuzumab and pertuzumab for breast cancer was reported as a rare finding (one case of twenty-nine patients). To our knowledge, this is one of the first cases describing an ODS following therapy with pertuzumab, trastuzumab, and docetaxel. <b>Disclosure:</b> Dr. Gaitan Alfonso has nothing to disclose. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BIIB. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. Ms. Rodriguez has nothing to disclose. Dr. Salej has nothing to disclose. Dr. Otero has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. Dr. Otero has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen . Dr. Otero has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for FICMAC. Dr. Toro has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Watch Neurology .

Early prediction of neoadjuvant treatment outcome in locally advanced breast cancer using parametric response mapping and radial heterogeneity from breast MRI.

Early prediction of nonresponse is essential in order to avoid inefficient treatments. To evaluate if parametrical response mapping (PRM)-derived biomarkers could predict early morphological response (EMR) and pathological complete response (pCR) 24-72 hours after initiation of chemotherapy treatment and whether concentric analysis of nonresponding PRM regions could better predict response. This was a retrospective analysis of prospectively acquired cohort, nonrandomized, monocentric, diagnostic study. Sixty patients were initially recruited, with 39 women participating in the final cohort. A 1.5T scanner was used for MRI examinations. Dynamic contrast-enhanced (DCE)-MR images were acquired at baseline (timepoint 1, TP1), 24-72 hours after the first chemotherapy (TP2), and after the end of anthracycline treatment (TP3). PRM was performed after fusion of T1 subtraction images from TP1 and TP2 using an affine registration algorithm. Pixels with an increase of more than 10% of their value (PRMdce+) were corresponding nonresponding regions of the tumor. Patients with a decrease of maximum diameter (%dDmax) between TP1 and TP3 of more than 30% were defined as EMR responders. pCR patients achieved a residual cancer burden score of 0. T-test, receiver operating characteristic (ROC) curves, and logistic regression were used for the analysis. PRM showed a statistical difference between pCR response groups (P < 0.01) and AUC of 0.88 for the prediction of non-pCR. Logistic regression analysis demonstrated that PRMdce+ and Grade II were significant (P < 0.01) for non-pCR prediction (AUC = 0.94). Peripheral tumor region demonstrated higher performance for the prediction of non-pCR (AUC = 0.85) than intermediate and central zones; however, statistical comparison showed no significant difference. PRM could be predictive of non-pCR 24-72 hours after initiation of chemotherapy treatment. Moreover, the peripheral region showed increased AUC for non-pCR prediction and increased signal intensity during treatment for non-pCR tumors, information that could be used for optimal tissue sampling. 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:1403-1411.

Abstract 3878: A model to assess clonal evolution of metastatic colorectal cancer during chemotherapy utilizing patient derived xenografts

Abstract Introduction Chemotherapy (FOLFOX) with or without surgical resection is the primary treatment for metastatic colorectal cancer (mCRC). However, intrinsic and acquired resistance to chemotherapy poses a major obstacle. The lack of predictors of response to treatment and of understanding of mechanisms of resistance leads to ineffective chemotherapy and, hence, unnecessary morbidities. Patient-derived xenografts (PDXs) represent a model system to evaluate the effectiveness of treatment regimens utilizing human tumors in the context of “precision medicine.” We have developed a heterotopic PDX model of mCRC that emulates acquired chemoresistance. Methods Tumor samples from treatment naïve or chemo-treated mCRC patients were implanted subcutaneously into immunodeficient mice. At an optimal volume, the tumor was either divided into pieces and implanted subcutaneously or processed into a single cell suspension and implanted into mice. Mice were classified into either 5-fluorouracil, leucovorin, plus oxaliplatin (FOLFOX) (n = 10) or vehicle (n = 5) groups. FOLFOX was dosed weekly at the maximum tolerated dosage. Mice were sacrificed when tumors reached 20mm diameter, at which time a single cell suspension was created for implantation into the next generation. Tumors were passaged using this method until FOLFOX resistance was attained. DNA and RNA were isolated from all samples for genetic analysis. Results Liver metastasis from six patients, including chemo-treated (n = 3) and chemo-naïve (n = 3), were consecutively used to generate PDX lines. PDX tumor growth from one of the patients exhibited no difference between treatment and control. Within the remaining treatment cohorts, chemo-treated PDX tumors overall grew significantly slower than matching untreated PDX tumors at the first passage (p&amp;lt;0.05) regardless of whether the tumor originated from single cell suspension or pieces. However, PDX tumors from the first patient entered into the study showed chemo-resistance at passage 3. Further, innate resistance was seen in some PDXs from the same patient displaying rapid growth at initiation of chemotherapy treatment. Utilizing tumor tissue obtained from this model, we are currently assessing the genetic and epigenetic mechanism(s) responsible for resistance. Conclusion We have developed a PDX model that recapitulates acquired chemoresistance in mCRC, which allows for the genomic characterization of FOLFOX resistant liver metastasis. We are currently defining the clonal architecture of chemotherapy resistant and responsive PDXs with the goal of identifying predictors of response and resistance. The ability to treat a patient and their personalized “model” in real time represents an ideal tool to test response to treatment and further investigate treatment resistance. Citation Format: Julie G. Grossman, Matthew Strand, Ha Dang, Brian White, Timothy Fleming, Peter Goedegebuure, Albert Lockhart, Kian Lim, Timothy Ley, Richard Wilson, Elaine Mardis, Christopher Maher, Ryan Fields. A model to assess clonal evolution of metastatic colorectal cancer during chemotherapy utilizing patient derived xenografts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3878. doi:10.1158/1538-7445.AM2015-3878

A proposed model for prediction of survival based on a follow-up study in unresectable pancreatic cancer

ObjectivesTo define an easy-to-use model for prediction of survival time in patients with unresectable pancreatic cancer in order to optimise patient' care.DesignAn observational retrospective study on patients with unresectable pancreatic...

Predictors of Early Death Risk in Older Patients Treated With First-Line Chemotherapy for Cancer

Objective factors for making choices about the treatment of elderly patients with cancer are lacking. This investigation aimed to help physicians select appropriate treatments through the identification of factors that predict early death (< 6 months) after initiation of chemotherapy treatment. Previously untreated patients greater than 70 years of age who were scheduled for first-line chemotherapy for various types of cancer were included. Baseline abbreviated comprehensive geriatric assessment (aCGA), including the Mini-Mental State Exam, Timed Get Up and Go (GUG), Activities of Daily Living (ADL), Instrumental Activities in Daily Living (IADL), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS15), and comorbidities index (Cumulative Index Rating Scale-Geriatric), was carried out. Prognostic factors of early death were sought from aCGA results and traditional oncology measures. A total of 348 patients were included across 12 centers in Southwest France (median age, 77.45 years; ratio of men to women, 1.47; advanced disease, 65%). Abnormal aCGA scores were observed for 18.1% of patients on the ADL, 73.0% of patients on the IADL, 24.1% of patients on the GUG, 19.0% of patients on the MMS, 44.0% of patients on the GDS15, and 64.9% of patients on the MNA. Advanced disease (odds ratio [OR], 3.9; 95% CI, [1.58 to 9.73]), a low MNA score (OR 2.77; 95% CI, [1.24 to 6.18]), male sex (OR, 2.40; 95% CI, [1.2 to 4.82]), and long GUG (OR, 2.55; 95% CI, [1.32 to 4.94] were associated with higher risk of early death. In patients greater than 70 years of age with cancer, advanced disease, a low MNA score, and poor mobility predicted early death. We recommend that the MNA and GUG, performed by a trained nurse, be maintained as part of routine pretreatment workup in these patients to identify at-risk patients and to inform the decision-making process for chemotherapy.

Trends in chemotherapy and biologic treatment of U.S. metastatic colorectal cancer patients

6553 Background: Several long-standing chemotherapy regimens are available to treat metastatic colorectal cancer (mCRC) including: oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (FOLFOX); and Irinotecan plus 5-FU and leucovorin (FOLFIRI). More recently, new biologic therapies were approved for use in mCRC. This cohort study examines trends in first-line chemotherapy treatments for newly diagnosed mCRC patients after the introduction of capecitabine (CAP) in 2001 and the biologic therapies in 2004. Methods: Using a large, US-based administrative medical claims database of a national commercially insured population, patients with newly diagnosed mCRC were identified from 2001 to 2005. At least 6-months of patient history prior to mCRC diagnosis were required to confirm patients were newly diagnosed. Patients were followed from initial mCRC diagnosis to death, disenrollment, or 12/31/2006. Results: Total of 3,781 newly diagnosed mCRC patients were identified between 2001–2005. On average over the 5 years, 58% of patients (with annual variation ± 4% points) received chemotherapy/biologic treatment in the year following their mCRC diagnosis; mean days to initiation of chemotherapy treatment decreased from 135 to 62 between 2001–2005. In 2001, FOLFIRI (40%), 5-FU (30%), and CAP (20%) were the most prevalent first-line treatments. In 2005, first-line treatment regimens were more diverse: FOLFOX plus bevacizumab (35%), FOLFOX alone (15%), 5-FU (15%), and CAP (15%) were the most prevalent, while 33% of patients used other treatment combinations. Among mCRC patients diagnosed in 2005, 63% were treated with at least one biologic therapy in the first year after diagnosis (57% received bevacizumab; 26% received cetuximab). Conclusions: While rates of chemotherapy use remained relatively constant between 2001–2005, patients initiated chemotherapy treatment sooner after their initial diagnosis and the standard course of therapy shifted from being FOLFIRI-based to FOLFOX-based. A rapid uptake in biologic therapies occurred. The majority of newly diagnosed mCRC patients were users of biologic therapy within one year following their introduction. [Table: see text]

Turnaround time for treatment of patients with colorectal cancer

17548 Background: Colorectal cancer is one of the leading causes of deaths in the United States. Depending on cancer staging and other co-morbidities, patients require either first, second, or third line chemotherapy regimens, which are paid for through a health insurance plan. Based on insurance plan policies and criteria, the turnaround time for treatment can take weeks before treatment initiation. Chemotherapy induced neutropenia and/or anemia may result from chemotherapy. Methods: A retrospective study was performed on patient charts in which 180 patients, in groups of 20, represented six of the major insurance companies seen in the Westchester Hematology/Oncology Private Practice. These charts were analyzed to calculate the average turnaround time for treatment administration and the correlation between this turnaround time and the cost of treatment. Results: Insurance companies which required specialty pharmacies and preauthorizations such as AETNA, Blue Cross Blue Shield (BCBS), and HIP had the longest turnaround times for treatment, averaging from 9–19 days for all types of treatment. This was followed by insurance companies that required patients to obtain treatment from a local pharmacy such as UHS and GHI, averaging from 6–15 days for all types of treatment. Medicare, which allowed patients to obtain treatment directly from the office had the shortest turnaround time in treatment, averaging from 3–11 days. Patients with chemotherapy induced neutropenia/anemia were forced to stop treatment until medications were obtained and bloodwork returned to normal, further delaying the turnaround time for subsequent treatments. In addition there was a direct correlation between the turnaround time for treatment and the cost of treatment for all insurance companies. Conclusion: Based on insurance policy, the initiation of chemotherapy treatment can be delayed. Studies indicate that delays in treatment can increase the log growth of cancer cells. Patients and physicians are forced to wait, appeal and sometimes fight with the insurance company for treatment reimbursement. In addition, chemotherapy induced neutropenia/anemia requires treatment to be halted. Studies indicate that such dose delays may allow more tumor regrowth between cycles. No significant financial relationships to disclose.

Early Detection and Successful Treatment of Drug-Induced Pneumonitis with Corticosteroids

A 69-year-old patient with non-small cell lung cancer developed pneumonitis with the use of the chemotherapeutic drugs gemcitabine, paclitaxel, and vinorelbine. He developed progressively worsening dyspnea, fevers, chills, and night sweats three weeks after initiation of chemotherapy treatment with no improvement with antibiotics. Bronchoscopic lung biopsy and endotracheal cultures were negative. Four weeks after the onset of symptoms, chest computed tomography scan showed a ground glass appearance of the lung parenchyma bilaterally consistent with pneumonitis. Gemcitabine is a nucleoside analog with activity against solid tumors, including breast and non-small cell lung cancers. Pneumonitis is a rare and potentially deadly complication of gemcitabine. Early treatment with corticosteroids leads to a complete resolution of this patients pneumonitis. Gemcitabine was discontinued and his chemotherapeutic regimen was changed to include paclitaxel, vinorelbine, and topotecan with no recurrence of pneumonitis. Pneumonitis should be included in the differential diagnosis of dyspnea in patients undergoing gemcitabine-based chemotherapy.

Eliciting preferences for alternative drug therapies in oncology: Influence of treatment outcome description, elicitation technique and treatment experience on preferences

Several methodologic issues arise in eliciting preferences for therapy. Examples are the selection of appropriate descriptions of treatment outcomes and of elicitation techniques. Of particular importance is the correspondence of patients' anticipated preferences for treatment to actual preferences once they have experienced treatment. Treatment outcome descriptions and elicitation techniques were compared for a hypothetical drug decision problem involving trade-offs between quality and quantity of life. Preferences of 54 cancer patients were elicited before, and 6 weeks following initiation of chemotherapy treatment. Patients' preferences were not influenced by the way information about side effects was presented, nor the stated probability of survival at high and moderate levels. A riskless rating technique produced different preferences from those of a risky treatment choice method. Although patients experienced significant toxicity following initiation of treatment, their preferences remained stable on retest. The results raise questions about the extent to which patients are willing, at the time of decision making, to trade off survival rate for improved quality of life.