tbuckley/cabot-search huggingface dataset:
Functional morbidities in patients ≥ 65 years compared with younger patients undergoing organ preservation therapy (OPT) for squamous cell carcinoma (SCC) of larynx (L) or propharynx (OP)
Authors: J. Ramanarayanan, M. Burstein, F. A. Brodzik, A. I. Jackson, S. Mehdi
Journal: Journal of Clinical Oncology (2007)

16533 Background: Advanced age is shown to be associated with increased late toxicity and minimal clinical benefit in head and neck cancer patients receiving aggressive or combined modality therapies. Elderly may also have delayed functional recovery after OPT. We conducted a retrospective study in patients = 65 years with L or O SCC undergoing OPT to compare functional outcome/ recovery with younger patients undergoing similar treatment. Methods: Patients with L or O SCC from January 1996-January 2006 who underwent OPT were retrospectively studied and stratified into 2 groups: = 65 or &lt; 65 years based on age at diagnosis. Dysphagia, gastrostomy (g) tube dependence, speech quality and weight loss at diagnosis, 3 and 9 months post therapy were compared. Swallowing and speech were evaluated by 2 specially trained therapists based on the Swallowing Performance Scale and GBRAS Scale (perceptual impression of voice quality) respectively. Student z-test and t-test were used in statistical analysis for comparison between patient proportion and mean values. Results: One hundred and twenty patients (L 74 and OP 46) received OPT, of which 43 were excluded (recurrence/inadequate records). Of the 77 (L 54 and O 23) patients analyzed (KPS 80–100), 44 (57%) were = 65 and 33 (43%) &lt;65; more patients aged &lt;65 had advanced stage; 14 patients (31%) = 65 and 16 (48%) &lt;65 received CRT or altered fractionation RT, rest of the patients received standard RT. Elderly group had greater proportion of patients with continued weight loss and higher incidence of dysphonia (70% vs 43% z-score 2.97, p=0.003) at 3 and 9 months than younger patients. Of 19 patients in the elderly group with g-tube, 13 were g-tube dependant at 3 months (68%) vs 12/23 (52%) in the younger population. Conclusions: Elderly may have persistent functional morbidity compared to younger patients receiving similar OPT. As the goal of OPT is to improve functional outcome, careful assessment of risk benefit ratio in the elderly is warranted before administering aggressive therapies. No significant financial relationships to disclose.
Treatment sequencing of abiraterone and enzalutamide in patients with mCRPC.
Authors: Allison H. Feibus, Ashwin Vasudevamurthy, Jeffrey R. Guccione, Elisa M. Ledet, Patrick Cotogno, Charlotte Manogue, Emma M. Ernst, Brian E. Lewis, Jonathan L. Silberstein, Oliver Sartor
Journal: Journal of Clinical Oncology (2017)

233 Background: Abiraterone (Abi) and Enzalutamide (Enza) are among the treatment modalities available for treating metastatic castrate-resistant prostate cancer (mCRPC). This study aimed to analyze the efficacy of Abi and Enza as direct sequential treatments for patients with mCRPC. Methods: A single institution retrospective review was performed on 66 patients, in which 52 (79%) of the patients received Enza following Abi. The primary outcome measure was PSA response (50% PSA decline). Patients treated with taxanes between Abi and Enza were excluded from these analyses. Results: In patients treated first with Abi and second with Enza (n = 52), 35/52 (67%) responded initially to Abi. Following PSA progression or lack of initial response, all 52 patients were then treated with Enza, and 15/52 (29%) responded. Of the 17 patients that did not initially respond to Abi, 9 (53%) patients had a PSA response to Enza, in which 5/9 had a PSA decline ≥ 50%. 14 patients had a PSA decline ≥ 50% on initial Abi only (no PSA declines at all were noted post-Abi) and 3/14 responded to Enza. The median duration on the 1 st drug was 294 days; median duration on the 2 nd drug was 89 days. Conclusions: Additional investigation is needed for clinicians to understand better the cross resistance of Abi and Enza in mCRPC patients. [Table: see text]
Total and cancer-attributable phase-based costs for childhood cancer care: A population-based study in British Columbia, Canada.
Authors: Mary L McBride, Ross Duncan, Karen Bremner, Claire De Oliveira, Ning Liu, Paul C. Nathan, Paul C. Rogers, Stuart Peacock, Murray Dale Krahn
Journal: Journal of Clinical Oncology (2017)

11 Background: Childhood cancer presents unique issues regarding treatment, late effects, and long-term survival, but few studies have reported costs. Childhood cancer-specific costs are useful for economic evaluation and planning care. This study estimates total and cancer-attributable (net) medical costs for a population-based childhood cancer cohort in British Columbia, Canada, by phase of care. Methods: Patients diagnosed with cancer at ages 91 days to 14 years between 1995-2009 were identified from the British Columbia Cancer Registry, and followed to December 31, 2010. Data were linked with clinical and provincial administrative healthcare databases covering all medically-necessary costs. Total resource-specific costs (Canadian $ 2012) were estimated overall and for patients with leukemia, lymphoma, central nervous system (CNS), and “other” cancers. Net costs were calculated by subtracting healthcare costs for propensity-score-matched provincial samples of children without cancer from cancer patient costs. Results: Of the 1,440 cases, 33% had leukemia, with 23% CNS tumours, 10% lymphoma, 34% other cancers; 93% survived &gt;=1 year. Overall pre-diagnosis mean costs per patient were $4,633, of which $4,555 was attributable to the cancer. Overall initial (first-year) mean costs were $97,780 ($97,254). Overall continuing phase mean costs were $12,441 ($12,006). Overall final year of life mean costs were $284,201 ($283,652). Cancer types with highest costs were CNS (pre-diagnosis), leukemia (first-year), “other” cancers (continuing), and lymphoma (end-of-life). Virtually all inpatient hospitalizations were cancer-related, representing ~41% of pre-diagnosis, ~71% of first-year, ~57% of continuing, and ~73% of end-of-life costs. Conclusions: Management of childhood cancer is costly, and is higher than for adolescent cancer in all phases of care, reflecting greater morbidity and treatment complexity. Hospitalizations were the largest driver of costs in all post-diagnosis phases of care. Costs in the continuing phase, including surveillance and care for late effects, were 13% of first-year phase costs.
A phase 3 randomized trial of veliparib (ABT-888) plus carboplatin and paclitaxel versus investigator’s choice of standard chemotherapy in previously untreated patients with metastatic/advanced non-squamous (NSq) non-small cell lung cancer (NSCLC).
Authors: Mark D. McKee, Michelle Pedersen, Angela DeLuca, Qin Qin, Jane Qian, Jade Irving, Peter Ansell, Terri Leahy, Courtney Caskey, Vincent L. Giranda
Journal: Journal of Clinical Oncology (2015)

TPS8106 Background: Standard chemotherapy for patients (pts) with metastatic NSq NSCLC consists of 4−6 cycles of platinum-based doublet therapy +/– subsequent maintenance monotherapy. Clinical outcomes are generally poor, with the majority of pts surviving ~1 year. Veliparib is a potent, orally bioavailable PARP1/2 inhibitor shown to enhance antitumor activity of platinum-based therapy in preclinical models. A recent phase 2 trial suggested that the addition of veliparib to carboplatin (C) and paclitaxel (T) may provide clinical benefit in pts with NSCLC (Ramalingam et al, Ann Oncol 2014;25(Suppl 4):1234P). Smoking status was a strong predictor of efficacy for veliparib-chemotherapy combination in advanced NSCLC. This study compares veliparib plus C and T with investigator’s choice of chemotherapy in NSq NSCLC. Methods: This is a randomized, multicenter, open-label trial (NCT02264990). Current or former smokers ( ≥ 18 years) who have received no prior chemotherapy for advanced/metastatic NSq NSCLC are randomized 1:1 to veliparib (120 mg p.o. BID on Days −2 through 5 of each 21-day cycle) plus C (AUC 6 mg/mL/min i.v. on Day 1) and T (200 mg/m2 i.v. on Day 1), or investigator’s choice of chemotherapy (C + T, or C + pemetrexed [P], or cisplatin + P). Randomization is stratified by smoking status, investigator’s preferred platinum therapy, gender, and ECOG PS. Treatment continues for a maximum of 6 cycles, or until disease progression or unacceptable toxicity. Pts in either arm may receive maintenance P (500 mg/m2 i.v. q3 weeks). The trial tests if combination treatment with veliparib improves survival in current smokers (primary objective) and in the overall population (secondary objective) compared with investigator’s choice of chemotherapy. PFS and objective response rate are also compared between the 2 treatment arms, both in current smokers and the overall population. Duration of overall response, safety, tolerability, ECOG PS, and quality of life are evaluated. Recruitment began in Oct 2014 and 525 pts are planned to be included. Clinical trial information: NCT02264990.
Implementing population-based screening for Lynch syndrome.
Authors: Lars Henrik Jensen, Anders Bojesen, Lene Byriel, Michael Hardt-Madsen, Katrine Urth Hansen, Christian Ladefoged, Jan Lindebjerg, Tine Plato Hansen, Lillian Bomme Ousager, Inge Bernstein
Journal: Journal of Clinical Oncology (2013)

6600 Background: A myriad of molecular markers has been proposed and tested with the promise of improving cancer care. Few have been validated and even fewer have been implemented in daily clinic. The most common hereditary colorectal cancer entity, Lynch Syndrome, can be identified in a subset of colorectal cancer patients by screening molecular markers for mismatch-repair (MMR) deficiency. We wanted to implement this screening in a Danish region, optimize quality, and describe the results. Methods: All colorectal cancer (CRC) patients diagnosed from October 2010 to September 2012 in the Region of Southern Denmark were included. Immunohistochemistry (IHC) was performed for protein expression of the MLH1, PMS2, MSH2, and MSH6 genes followed by MLH1 methylation analysis in cases with loss of pMLH1. Hereafter the indications for genetic counselling were lack of any MMR-protein – and in case missing pMLH1only those with no promoter-methylation of MLH1. Patients were included irrespectively of stage, post-mortem diagnosis, surgery, or other treatment. Accepted reasons for missed data were insufficient or autolyzed tumor material, but not data missing due to death, no surgery, or any logistic problem. Every 3-6 months the national pathology database was checked for missing data and feedback was given to the clinicians to ensure enrolling of all CRC patients. Results: CRC were diagnosed in 2,120 patients in a population of 1,200,000 with informative data for 1,932 patients at the time of analysis. 1,680 had normal protein expression of all four MMR-genes. 209 lacked pMLH1 of which 11 were not methylated. Loss of pMSH2, isolated pMSH6 or pPMS2 was seen in 23, 11, and 9 cases, respectively. Thus, the established screening program was positive in 54 patients. These patients are offered further genetic counselling and testing. Conclusions: Screening for Lynch Syndrome was feasible in a geographically defined area involving several clinical departments. Molecular screening for hereditary MMR-deficiency was positive in 54 of 1932 patients (2.8 %). Implementation of molecular markers in cancer care can be optimized by support from national databases and formalized quality feed back to the clinicians. Clinical trial information: NCT01216930.
POSNOC: Positive sentinel node—Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy: A randomised trial looking at axillary treatment in early breast cancer (ISRCTN54765244).
Authors: Amit Goyal, Robert E. Coleman, David John Dodwell, Lesley Fallowfield, Valerie A. Jenkins, Bruce Mann, Malcolm W Reed
Journal: Journal of Clinical Oncology (2015)

TPS1103 Background: Women with early breast cancer that has spread to 1 or 2 sentinel nodes (SNs) undergo axillary node clearance (ANC) or axillary radiotherapy (ART). The publication of the Z11 trial challenged this practice. There are however concerns about this trial which may limit the interpretation and generalisability of its results. These issues include the proportion of patients with micrometastases, variability in radiotherapy and applicability in patients undergoing mastectomy. Therefore further randomized trials are needed to define the role of axillary treatment in patients with 1 or 2 SNs with macrometastases. The UK-ANZ POSNOC trial is asking this question and will provide a more solid evidence base to inform clinical practice. Methods: Trial design: A pragmatic, randomized, multicenter, non-inferiority trial. Interventions:All participants will receive systemic adjuvant therapy according to local guidelines and radiotherapy to breast or chest wall if indicated. Women in the intervention group will receive systemic adjuvant therapy alone, whereas those receiving standard care will receive adjuvant therapy plus ANC or ART. Study population: Women with unifocal or multifocal invasive breast cancer( ≤ 5 cm) undergoing breast conserving surgery or mastectomy, node-negative by clinical and ultrasound examination, who have 1 or 2 nodes with macrometastases at SN biopsy and no extranodal extension. The sample size is 1900 women. All participants will be followed up for 5 years. Primary outcome: axillary recurrence at 5 years. Secondary outcomes: arm morbidity, quality of life, anxiety, loco-regional recurrence, distant metastasis; time to axillary recurrence, axillary recurrence-free survival, disease-free and overall survival, contralateral breast cancer, non-breast malignancy and economic evaluation. Key differences from Z11: a) stringent radiotherapy quality assurance program, b) prospective pathology reporting, b) axillary ultrasound is mandatory, b) mastectomy patients are eligible, c) axillary treatment in the standard group may be ANC or ART. Current enrollment: 35 patients. Clinical trial information: ISRCTN54765244.
Statin polyp prevention trial in patients with resected colon cancer: NSABP protocol P-5.
Authors: Bruce M. Boman, Hanna Bandos, D. Lawrence Wickerham, Nicholas J. Petrelli, Michael J. O'Connell, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

TPS1615 Background: HMG-CoA reductase inhibitors (statins) are effective lipid-lowering agents that are used for treating hyperlipidemia. Results from cell culture, animal experiments, and epidemiologic studies indicate that statins may be active chemopreventive agents against colorectal cancer (CRC). However, the clinical studies come largely from retrospective, observational studies originally designed to investigate lipid-lowering or cardiovascular endpoints rather than tumor endpoints. Methods: NSABP P-5 is a randomized, prospective placebo-controlled, double-blind study of rosuvastatin (10 mg per day x 5 years) or placebo for the prevention of adenomatous polyps of the colon or rectum, metachronous colorectal carcinoma, and colon cancer recurrence. Additional secondary endpoints include the size, number and features of the colorectal adenomas as well as health-related quality of life and self-reported symptoms. Selected Eligibility: (1) Patients who have undergone complete resection of AJCC Stage I or II colon cancer within 1 year before randomization. (2) Colonoscopy within 180 days before randomization. Selected Ineligibility: (1) Hyperlipidemia, (2) Familial Adenomatous Polyposis, (3) Lynch Syndrome. Sample Size:1,740 patients will be entered, and as of January 23, 2012, 163 (9.37%) have been randomized. The study is open at NSABP and CTSU sites in North America. Funded by NCI PHS grants U10-CA-37377 and U10-CA-6974, with additional funding from AstraZeneca Pharmaceuticals, LP.
Phase 1b study of ONT-380, an oral HER2-specific inhibitor, in combination with capecitabine (C) and trastuzumab (T) in third line + treatment of HER2+ metastatic breast cancer (MBC).
Authors: Erika Paige Hamilton, Denise A. Yardley, Gabriel N. Hortobagyi, Luke N. Walker, Virginia F. Borges, Stacy L. Moulder
Journal: Journal of Clinical Oncology (2015)

602 Background: ONT-380, a potent, highly selective, small molecule inhibitor of HER2, was associated with clinical benefit and minimal EGFR-type toxicities in a phase 1 single agent study in HER2+ MBC. Based on synergistic activity with chemotherapy and T in preclinical models, ONT-380 is being evaluated in combination with C and T in pts with HER2+ MBC following prior treatment with T and ado-trastuzumab emtansine (T-DM1). ONT-380 300 mg PO BID was well tolerated in combination with either C or T alone, and is now being studied in combination with both C and T as triplet therapy. Methods: Phase 1b 3+3 dose escalation study with expansion cohort for a total of 15 pts at a given dose. ONT-380 (300 mg PO BID), C (1000 mg/m2 PO BID 14 days of a 21-day cycle), and T (8 mg/kg IV loading; then 6 mg/kg IV once every 21 days), are administered to HER2+ MBC pts previously treated with trastuzumab and T-DM1. Prior pertuzumab, lapatinib, or neratinib, and asymptomatic brain metastases (treated or untreated) are allowed. Assessments include safety, tumor response by RECIST 1.1, and PK. Results: 8 pts (# prior treatments for MBC 2-6) have completed 2–8 cycles of triplet therapy; 6 pts remain active. A dose-limiting toxicity (DLT) of reversible cerebral edema with Gr 3 dysarthria and visual field deficit was seen in a pt with known brain metastases. No additional DLTs were seen. Most toxicities have been Gr 1 or 2; the most common being nausea, vomiting, diarrhea, palmar-plantar erythrodysaesthesia, and fatigue. One additional Gr 3 treatment-related event of reversible increase in AST/ALT was reported. No Gr ≥ 3 diarrhea has been seen. To date, best responses in pts with at least 1 follow up scan have been: partial response (PR) n = 4, stable disease (SD) n = 2, and progressive disease n = 2. Two pts with PR and 2 pts with SD also had received prior pertuzumab. Conclusions: ONT-380 in combination with C and T exhibits an acceptable safety profile without Gr 3 diarrhea. The combination shows preliminary evidence of disease control in heavily pre-treated HER2+ MBC pts with prior exposure to trastuzumab, pertuzumab, and T-DM1. Enrollment in an expansion cohort is ongoing. Clinical trial information: NCT02025192.
A drug-drug interaction study between the strong CYP3A4 inhibitor ketoconazole (keto) and ixazomib citrate (MLN9708), an investigational, orally active proteasome inhibitor, in patients with advanced solid tumors or lymphoma.
Authors: Neeraj Gupta, Karthik Venkatakrishnan, Dennis A Noe, Michael J Hanley, Jiang Yu, Alberto Bessudo, Sunil Sharma, Robert Matthew Strother, Yaping Shou, John J. Nemunaitis
Journal: Journal of Clinical Oncology (2013)

2555 Background: MLN9708 is an oral proteasome inhibitor currently being investigated in multiple myeloma and amyloidosis in phase 3 studies. MLN9708 immediately hydrolyzes to its biologically active form, MLN2238, in aqueous solutions or plasma. Metabolism by multiple cytochrome p450s (CYPs) including 3A4 and 1A2 (&gt;25% contribution by each) was expected to be the primary clearance mechanism for MLN2238 based on human liver microsomal metabolism studies. This open-label, multicenter study (NCT01454076) characterizes the effect of CYP3A4 inhibition with keto on single-dose pharmacokinetics (PK) of MLN9708 in a fixed sequence design. Methods: Patients received MLN9708 2.5 mg on d 1 and 15, and keto 400 mg (PO) daily on d 12–25. On d 15, MLN9708 and keto were administered concomitantly. Serial blood samples were collected over 0–264 hr after MLN9708 doses on d 1 and 15 for PK characterization. Plasma PK parameters were estimated by non-compartmental methods. The effect of keto co-administration on MLN9708 AUC 0–264hr and C max was evaluated by Analysis of Variance of log-transformed values. Results: 16 PK-evaluable patients (11 Caucasian, 3 African American, 2 Hispanic; 6M, 10F) with mean (range) age of 61 years (48–79) and body surface area of 1.8 m 2 (1.5–2.3) were enrolled. Co-administration of MLN9708 and keto resulted in a 2-fold increase in MLN9708 AUC 0–264hr but no change in C max (Table). No differences in adverse events were observed +/- the addition of keto, to a single dose of 2.5 mg MLN9708. Conclusions: The observed 2-fold increase in MLN9708 AUC 0–264hr with a strong CYP3A4 inhibitor suggests the contribution of CYP3A4 clearance to the total clearance of MLN9708 is significant. These results support the continued exclusion of strong CYP3A4 inhibitors in ongoing and planned clinical trials of MLN9708. Clinical trial information: NCT01454076. [Table: see text]
Trends in body mass index (BMI) during and after treatment for standard risk (SR) acute lymphoblastic leukemia (ALL): A report from the Children’s Oncology Group (COG).
Authors: Susan Joy Lindemulder, Linda C. Stork, Bruce C. Bostrom, Xiaomin Lu, Meenakshi Devidas, Joseph Philip Neglia, Nina Kadan-Lottick
Journal: Journal of Clinical Oncology (2012)

9546 Background: Obesity is a potential complication in children treated for ALL. Limited data exist regarding timing of BMI changes and risk in long-term survivors of ALL treated without cranial radiation (CRT). This study describes temporal trends in BMI during and after therapy for SR-ALL and identifies associated factors. Methods: We conducted a retrospective cohort study of children with SR-ALL enrolled on two sequential clinical trials between 1993 and 2000 and on the COG ALTE02C2 follow-up study. Therapy included prednisone or dexamethasone during induction, the same steroid in maintenance phases, and no CRT. Standing height and weight was ascertained at diagnosis (dx), start of consolidation, start of maintenance, start of the last cycle of maintenance, and at least one year off therapy. Age and gender-specific BMI percentiles (BMI%) were calculated using 2000 CDC growth charts for patients 2-20 years. Results: The 269 subjects were a median of 3.5 years at dx, 46.7% female, 82.3% white, and a median of 9.1 years since dx at the last timepoint. The BMI% was associated with elapsed time since dx: BMI% increased between dx and consolidation (50.9%-68.3%, p &lt; 0.0001), remained stably elevated until the end of maintenance, and then decreased somewhat from the end of maintenance to the last timepoint (74.1%-70.6%, p = 0.03). After therapy, 18.1% of survivors were overweight (BMI% 85-95) and 20.9% were obese (BMI% ≥ 95). By unadjusted linear regression, higher dx BMI% was positively associated with BMI% post-therapy (p &lt; 0.0001). There was an interaction with steroid and dx BMI% such that the association between dx BMI% and post therapy BMI% was significantly greater for the dexamethasone group than the prednisone group (p = 0.01). There was no association with age at dx, gender, or race. Conclusions: In this retrospective study of SR-ALL survivors treated without CRT, we found that BMI% increased significantly in the month after dx and remained substantially elevated even several years after the end of therapy. Dx BMI% was highly associated with off-therapy BMI%, particularly in patients who had received dexamethasone rather than prednisone.