tbuckley/cabot-search huggingface dataset:
Feasibility and efficiency of automatic treatment planning for stereotactic body radiation therapy (SBRT) in pancreatic cancer patients.
Authors: Avani Satish Dholakia, Joseph A. Moore, Aaron Tyler Wild, Wuyang Yang, Kim Evans, Todd McNutt, Joseph M. Herman
Journal: Journal of Clinical Oncology (2013)

323 Background: Overlap volume histogrmas (OVHs) allow for new plans to be generated based upon prior similar treatment plans. The purpose of this project was to clinically deploy a generic and user-friendly interface for using a database populated with OVHs for planning SBRT pancreas patients. An interface for evaluating adherence to protocol tolerances is also developed to aid in the planning process. Methods: A database of previously treated SBRT pancreas patients is used to query the organ at risk (OAR) dose from patients with similar or harder to plan OVHs. For each OAR in a new plan, the database is queried to find the lowest achievable structure dose from all previous patients with a greater than or equal overlap between the selected structure and the target structure. Queried values are then automatically loaded into the inverse planning optimizer objectives and used to generate an optimized plan. Plans are then evaluated using a protocol interface which queries relevant protocol values and displays the values in a color-coded interface. Upon plan completion the system submits the new patient data to the OVH database and stores relevant DVH metrics in the MOSAIQ database for tracking. Results: The interface has been used to successfully plan 5 SBRT patients. All planned patients met protocol requirements. Automatic plans required fewer iterations to produce an acceptable plan. The physician indicated preference to the automatically generated plans due to better adherence to protocol requirements and lower critical structure doses. Conclusions: Automatic planning can be used to generate clinical plans which reduce dose to normal tissues while achieving the dose distribution required by clinical protocols. The protocol interface allows for more rapid evaluation of plan acceptability during planning and for physician review. The system can be deployed clinically, but requires adherence by all participants to standard naming conventions for targets and OARs.
Vinorelbine in progressive unresectable low-grade glioma in children.
Authors: A. M. Cappellano, E. Bouffet, F. Silva, P. Paiva, M. T. d. S. Alves, S. Cavalheiro, N. S. Silva
Journal: Journal of Clinical Oncology (2011)

9524 Background: Low grade glioma represent 30-40% off all childhood brain tumors. Optimal treatment when feasible is surgical resection resulting in cure in the majority of the cases. However, the management of progressive unresectable low-grade glioma (PULGG) remains controversial. There is increasing evidence that chemotherapy can delay or even allow avoidance of radiotherapy and/or surgery in these unresectable tumors. Several protocols have been described. However, short and long term toxicity remains a major issue in this chronic disease. Within this context, we present our experience with single agent vinorelbine, a semi-synthetic vinca alkaloid. Methods:From July 2007 to January 2011, 32 patients with recurrent (10) or newly diagnosed (22) PULGG started treatment with vinorelbine 30 mg/m² on days 0, 8 and 22 for a total of 18 cycles. Tumor site was hypothalamic/chiasmatic (19), spinal cord (1), cortex (1), cerebellum (1), brainstem (4), multifocal (3) and 2 patients had gliomatosis. Four children had neurofibromatosis and 3 diencephalic syndrome. Twenty- two patients had prior neurosurgical intervention. Response criteria were based on magnetic resonance imaging and physical examination. Results: Twenty- eight patients (median age 7 years 1 month) were evaluable after 4 cycles of vinorelbine, with objective response (OR) in 9 patients, stable disease (SD) in 19. After 8 cycles, 25 patients were evaluable with 9 OR, 15 SD and 1 PD. After 18 cycles, 18 patients were evaluable for response, 5 with OR, 10 SD and 3 PD. Three patients died: one of disease progression, one of atypical pneumonia and one of tracheotomy obstruction. Toxicity was mild and manageable in most cases: Grade I/II gastrointestinal toxicity was observed in 9 patients, grade I/II neurotoxicity in 2 patients and grade IV hematologic toxicity in 3 patients. Conclusions: Our preliminary results suggest that vinorelbine is active in patients with ULGG. This drug offers several advantages including a low toxicity profile associated with excellent quality of life.
Complications of intrathecal pump therapy in malignancy-related pain.
Authors: Danielle M Noreika, Egidio Del Fabbro
Journal: Journal of Clinical Oncology (2016)

102 Background: Intrathecal pumps (ITP) are used to manage severe malignancy related pain by delivering analgesics directly into the cerebrospinal fluid, in theory allowing for a reduced opioid dose and fewer complications. Although there is literature to support efficacy in patients with cancer, including improved survival, this mode of drug delivery also carries a risk of serious complications. Reports of complications in non-malignant pain suggest the risks and mortality related to ITP may be under-appreciated and that injury and liability occur with both ITP placement and ITP maintenance. Additional burdens to consider in patients with cancer include accurate prognostication to identify appropriate candidates, and the logistics of providing ITP maintenance. Methods: A retrospective chart review of 26 consecutive patients that underwent implantation of a programmable ITP at a National Cancer Institute center between 2008 and 2014 for malignancy related pain. Results: 53% (n = 14) of patients experienced major and minor ITP complications. Major complications occurred in 35% (9) including leg weakness post operatively requiring wheelchair use for months; granuloma formation causing leg weakness and requiring repeat operation; pump infection leading to sepsis and death; intra-abdominal abscess; significant bleeding requiring discontinuation of therapeutic anticoagulation for PE; and neurological complications including delirium and protracted seizures requiring ICU admission. Minor complications occurred in 31% (8) and included wound infections, urinary retention requiring catheterization, foot drop, and spinal headaches related to CSF leaks. 42% (11) died &lt; 90 days after ITP implantation; 19% (5) died &lt; 30 days after ITP implantation. 7 patients (27%) were either lost to follow up, relocated, transitioned to hospice, or had difficulty finding providers to refill the pump. Conclusions: More than a third of patients with cancer receiving an ITP at our institution experienced major complications including death, sepsis, and neurological problems.
Association between certificate of need (CON) legislation and radiotherapy use among elderly patients with early cancers: A population-based examination.
Authors: Aaron David Falchook, Ronald C. Chen
Journal: Journal of Clinical Oncology (2014)

283 Background: High quality cancer care includes reducing overtreatment, a well-recognized problem for elderly patients with ductal carcinoma in situ (Stage 0) or Stage 1 breast cancer and low-risk prostate cancer. The federal Health Planning Resources Development Act of 1974 led to implementation of CON programs in multiple states. The stated purpose of CON is to facilitate coordinated health care services to reduce overall medical costs. We examined whether CON is associated with less radiotherapy (RT) use in elderly patients with Stage 0-1 breast cancer, and low-risk prostate cancer. Methods: We compared RT use in 6 Surveillance, Epidemiology and End Results (SEER) states with CON for radiotherapy vs. 6 states without CON for 1) men 65 years and older with low-risk prostate cancer, 2) women 70 years and older with Stage 0-1 breast cancer after lumpectomy. In both clinical scenarios, the use of RT is controversial. Patients diagnosed from 2004-2011 were included. Results: 40,267 men and 24,385 women were included. Radiotherapy use was higher in CON states: prostate cancer (64.3 vs. 56.0%, p&lt;.001), and breast cancer (59.5% vs. 53.6%, p&lt;.001) overall, and for each year studied (Table). RT use decreased from 2004 to 2011, but remains persistently higher in states with CON programs. On multivariate analysis controlling for age, race, stage and year, CON was associated with higher use in both prostate cancer (OR 1.46, p&lt;.001) and breast cancer (OR 1.35, p&lt;.001). Conclusions: There is more RT use in CON states for elderly patients who may not need this treatment for Stage 0-1 breast cancer and low-risk prostate cancer. This suggests that CON programs may not be effective in reducing overtreatment, an important quality of care issue in oncology. [Table: see text]
Development and validation of a prediction tool for hand-foot skin reaction (HFSR) in patients receiving sorafenib.
Authors: J. Yu, G. Dranitsaris, M. D. Vincent, L. Huang, F. Fang, M. E. Lacouture
Journal: Journal of Clinical Oncology (2011)

2605 Background: Sorafenib is active in advanced renal-cell and hepatocellular carcinomas. However, HFSR is a frequent adverse event (AE; all-grade, 60%; grade ≥2, 23%) that is associated with pain and may lead to inconsistent sorafenib dosing. Prediction of HFSR risk with validated mathematical models would be important in counseling and management strategies. We developed and validated a repeated-measures model to predict the risk of ≥ grade 2 HFSR by week of therapy. Methods: Data from 451 patients who received a sorafenib starting dose of 400 mg bid as part of a clinical trial were reviewed (Escudier et al, 2007). Generalized estimating equations were used to develop the final risk model using a backwards elimination process. Internal validation of the final regression coefficients was achieved using nonparametric bootstrapping. External validation was performed on a new sample of 1145 patients who received sorafenib under an expanded access program. A risk scoring algorithm (range, 0-60) was derived from final model coefficients. Predictive accuracy of the scoring system was measured by receiver operating characteristic curve (ROC) analysis. Results: Pretreatment white blood cell count, female gender, good performance status, presence of lung and liver metastases and total number of metastatic sites were identified as important predictors for ≥ grade 2 HFSR. A nonlinear association between HFSR risk and duration of therapy was also identified, whereby risk was maximized at Week 5, followed by a gradual decline. The ROC analysis on the internal and external validation datasets had acceptable areas under the curve of 0.67 (95% CI: 0.64-0.70) and 0.60 (95% CI: 0.59-0.62) respectively. Prior to each week of therapy, patients with risk scores >40 would be considered at high risk for developing ≥ grade 2 HFSR. Conclusions: Risk of ≥ grade 2 (moderate-severe) HFSR varies by weekly cumulative sorafenib exposure as well as patient and disease characteristics, with greater risk in females, ECOG PS 0, and ≥2 sites of metastases. The application and planned continued refinement of this prediction tool will be an important source of patient-specific risk information for the development of moderate to severe HFSR.
Phase 1 trial of KOS-862 (epothilone D) in combination with carboplatin (C) in patients with solid tumors
Authors: J. P. Monk, M. Calero-Villalona, J. Dupont, J. Larkin, G. Otterson, D. Spriggs, A. L. Hannah, G. F. Cropp, R. G. Johnson, M. L. Hensley
Journal: Journal of Clinical Oncology (2005)

2049 Background: KOS-862 shares a binding site on tubulin heterodimers with paclitaxel, but shows greater potency in P-glycoprotein MDR cell lines, causing G2/M arrest. Coadministration of KOS-862 + C using MV522 and SK-MES (human lung cancer cell lines) showed additive and sequence-independent antitumor activity. Based on single-agent data (including a lack of significant myelosuppression with KOS-862), the 2 agents may show non-overlapping toxicities. Study objectives were to define the MTD, toxicity and PK of these agents. Methods: To date, pts have received C (AUC 5 on D1) and KOS-862 (50 and 75 mg/m2 on D1 & 8) in 2 cohorts. Sequence of agents: Cremophor prophylaxis, KOS-862 (90 min IV) followed by C (30 min IV, Day 1 only). PK is performed for KOS-862, seco-KOS-862, and platinum. Sparse sampling for C was employed, with free platinum AUC calculated from 24h platinum. Results: 12 pts (6 F/6 M; median age 58 yrs; ECOG 1; prior regimens 2, range 1–5) were enrolled in 2 dose levels. Dose limiting toxicity (DLT) was observed in the 1st pt, consisting of 4-week delayed recovery of neutrophils. No other DLT was observed upon expansion of this cohort to 6 pts. At the 2nd dose level, one patient was noted to have grade 3 neurosensory toxicity; the cohort is still undergoing final assessment. Other drug-related toxicity (all Grade 1–2): neutropenia, N/V, asthenia, and neurosensory. KOS-862 PK (50 mg/m2): t½: 7.8±0.9h; Cmax: 955 to 4388 ng/mL; Vz: 167.6 ± 96 L. For the metabolite: AUCtot ratio parent:metabolite varied from 33–107% with Tmax (metabolite) 3/4h later than parent; t½ 11.5±6.2h; Cmax varied 166 to 840 ng/mL. For C (AUC=5) mean = 5.18±1.76 mg/mL*min. Antitumor activity observed in 1 pt with ovarian cancer with CR (resolution of psoas lesion; CA125 normalization) and 1 pt with HCC with 41% drop in AFP and SD for 21 wks. Conclusions: Accrual continues to define the recommended dose. Neutropenia has been observed more frequently in this trial compared to single-agent KOS-862. PK parameters for KOS-862 and C were unchanged compared to single-agent therapy of each. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Kosan Biosciences Kosan Biosciences Kosan Biosciences Kosan Biosciences
Phase II trial evaluating capecitabine and irinotecan in patients (pts) with esophago-gastric (E-G) carcinoma having progressed or relapsed within 3 months of platinum-based chemotherapy
Authors: L. Assersohn, A. R. Norman, G. Chong, G. Brown, P. J. Ross, C. Costello, L. Higgins, J. Oates, D. Cunningham
Journal: Journal of Clinical Oncology (2005)

4170 Background: To assess the efficacy and toxicity of a 3-weekly regimen containing capecitabine combined with irinotecan (CapeIri) in refractory or relapsed E-G carcinomas. Primary endpoints were response rate (RR) and disease free survival (DFS) with secondary endpoints of overall survival (OS) and toxicity. Methods: 29 pts with locally advanced or metastatic E-G carcinoma (27 adenocarcinoma, 2 squamous carcinoma) with documented progression during or within 3 months of completion of chemotherapy were recruited between January 2003 and November 2004. Capecitabine (2000mg/m2/day Day 1–14) and Irinotecan (250mg/m2 Day 1) (CapeIri) was given every 3 weeks. CT response was assessed at 12 and 24 weeks. Results: Four pts were ineligible due to no measurable disease (number, n=3) and progression > 3 months since platinum therapy (n=1). Median age of the 25 eligible pts was 59 years and 21 pts (84%) had metastatic disease. All pts had previously received platinum although one pt had capecitabine alone immediately prior to study entry. 19/25 (76%) received a 3-drug ECF-like regimen. At present, with a median follow up of 4.3 months, 21 pts are assessable for response. 3 pts responded, RR 14.3% (95% CI 3.1–36.3%) and 3 pts (14.3%) had stable disease. Improvement in the following tumor-related symptoms occurred: dysphagia 43% (3/7 pts), reflux 50% (5/10), anorexia 44% (4/9), weight loss 43% (3/7), vomiting 60% (3/5) and pain 29% (4/14). 8 pts (32%) had grade 3/4 neutropenia and 1 pt (4%) had febrile neutropenia. There were no toxic deaths. Median DFS was 2.8 months and median survival was 6.3 months. Conclusions: Second-line chemotherapy with CapeIri in primary refractory and relapsed esophago-gastric carcinoma is effective, tolerable palliative treatment and warrants further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Roche, sanofi-aventis Roche-educational grant and free drug. Money to research fund, sanofi-aventis towards drug costs, to research fund not myself.
Regional differences in efficacy/safety/biomarkers in a randomised study of axitinib in 2nd line patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: Masatoshi Kudo, Joong-Won Park, Shuntaro Obi, Shukui Qin, Eric Assenat, Yoshiko Umeyama, Debasis Chakrabarti, Olga Valota, Yosuke Fujii, Jean-Francois Martini, James Andrew Williams, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2016)

329 Background: A randomised, double-blind phase II study of axitinib plus BSC [AXI] vs placebo plus BSC [PBO] was conducted in HCC pts after failure of one antiangiogenic therapy. Primary outcome was presented at ESMO 2014. No significant differences in overall survival (OS) between two arms were noted overall and in pre-specified subgroup analysis (non-Asian [nA] and Asian [A]). Interestingly, improvements favouring AXI (P &lt; 0.01) were observed in secondary efficacy endpoints and retained among A. Methods: Exploratory efficacy/safety/biomarker analyses were performed by geographic region (nA; A; A subgroups: Japan/Korea [JK] and China/Hong Kong/Taiwan [CHT]) including: OS excluding pts intolerant to prior therapy; relationship between a subset of 26 baseline micro RNAs (miR) and AXI effect. Results: 78 nA pts (76% male, 60% with vascular invasion/extrahepatic spread) and 124 A pts (73JK/51CHT) (86% [84% JK, 90% CHT] male; 86% [82% JK, 92% CHT] with vascular invasion/extrahepatic spread) were randomized. In regional subgroups, OS HR excluding pts intolerant to prior therapy was: nA HR = 0.700 (95% CI 0.373–1.316; p = 0.1318) for AXI (45) vs PBO (16); A HR = 0.653 (95% CI 0.415–1.027; p = 0.0312) for AXI (76) vs PBO (35); JK HR = 0.479 (95% CI 0.250–0.918; p = 0.0118) for AXI (46) vs PBO (17); CHT HR = 0.918 (95% CI 0.480–1.756; p = 0.3954) for AXI (30) vs PBO (18). AXI safety profile was generally similar in regional subgroups. Differences were seen in dose modification pattern: dose reduction or discontinuation due to adverse events in 24% nA / 41% A / 51% JK / 26% CHT or in 39% nA / 22% A / 16% JK / 32% CHT, respectively. miR analysis for OS showed a trend of predictive and/or prognostic effect in overall population (e.g., let-7e-5p); a strong predictive effect of multiple miR (e.g., miR-3648) was seen in A but not in nA. Conclusions: AXI showed favorable OS vs PBO in nA and A, particularly in JK, when pts intolerant to prior therapy were excluded, suggesting that pts who progress on prior therapy are more suitable population for new agent studies in HCC. Appropriate dose modifications may also play a role in treatment duration. Baseline miR signature may have predictive value for AXI OS in A. Clinical trial information: NCT01210495.
Health risk assessment of head/neck cancer patients.
Authors: Andrew Salner, Ellen A Dornelas
Journal: Journal of Clinical Oncology (2014)

81 Background: Effective methods of screening head and neck cancer patients for health risk behaviors are needed. Methods: The present study assessed 452 cancer patients with an assessment that covered the following domains: psychological distress, smoking status, nutritional intake, functional activity level and need for support services. Thirty six out of the 452 patients recruitedfrom radiation oncology carried a diagnosis of head/neck cancer. Results: Patients with head/neck cancer had higher levels of depressive symptoms measured by the Patient Health Questionnaire (PHQ9) with mean scores of 6.3 (SD=4.8) compared to the scores of patients with other cancer diagnoses (mean PHQ9 score= 4.3, SD=5.4) p=.04. Twenty percent of head/neck patients had PHQ9 scores greater than 12 and 52% had a distress thermometer score of &gt;4. Head/neck patients were more likely to be current smokers or have quit since diagnosis (31%) compared to patients with other diagnoses (16%) p=.02. Head/neck patients were more likely to be male 68% (p&lt;.001). When asked if they would like services from any of the following practitioners, 29% requested a nutritionist, 14% requested a social worker and 25% requested integrative medicine services. None of the smokers with head/neck cancer requested services from the smoking cessation counselors compared to 25% of smokers with other cancer diagnoses. In the sample of head/neck patients, 73% of smokers were likely to endorse feeling “worry, fear or nervousness” compared to 33% of non-smokers (p=.04). Referrals were facilitated with an automated email to the clinician within 2 days of the assessment. Conclusions: Head/neck patients in this sample are more likely to have depressive symptoms and to have health risks such as smoking. Smokers are less likely to be receptive to smoking cessation counseling. Cumulatively, these data suggest that the needs of head/neck cancer patients are distinct and this diagnostic group may benefit from enhanced survivorship services both during treatment and to follow.
A phase I study of MM-10-001 in advanced non-small cell lung cancer.
Authors: M. C. Cristea, M. Koczywas, K. L. Reckamp, S. F. Lacey, A. Rotter, P. H. Frankel, S. Fouladi Rad, X. Liu, V. Tran, E. Reorizo, M. Kalos
Journal: Journal of Clinical Oncology (2011)

7572 Background: MM-10-001 is a bioactive agent exported from Shiitake Mycelium in aqueous medium. The beta-glucan in MM-10-001 binds to a lectin site within the complement receptor 3 on leukocytes, priming the receptor to trigger cytotoxic degranulation of leukocytes when leukocyte CR3 binds to iC3b-opsonized tumor cells. This phase I study was designed to assess the feasibility and toxicity of MM-10-001. Secondary endpoints included exploratory analysis of the effect of MM-10-001 on the innate immune compartment and the cytokine profile of the patients as well as antitumor efficacy. Methods: Patients with advanced NSCLC received orally escalating doses of MM-10-001 (5mg, 10 mg and 20 mg); a cycle consisted of 28 days. The blood samples for correlative studies were collected pre-study and weeks 1, 5, 9, 13. Serum cytokine levels were measured with 30-plex cytokine/ chemokine/growth factor multiplex panels (Invitrogen), and analyzed using a FLEXMAP-3D instrument (Luminex). Results: To date, 20 patients (7M/13F) have been treated (MM-10-001 5 – 20 mg). No grade 3+ treatment related adverse events were noted. Grade 2 adverse events reported are fatigue (3 pts), anorexia (1 pt), Alk Phos (1 pt), and joint pain (1 pt), each with an attribution of “possible”. Median time to treatment failure was 3.5 months (range 1-13+ months). Correlative studies on 19 cytokines in addition to immunoglobulins (A, M, G), WBC, hemoglobin, PLT, ANC, CRP, and serum complements C3 and C4 were conducted on 18/20 subjects. Significant cytokine increases were noted in 3 patients concurrent with progression, resulting in a positive trend in several cytokines over time. Subset analysis, excluding those patients, suggested a possible decrease in IL-12 as a function of both time and dose (p=0.01, 0.02 respectively), along with a decrease in MIP1b as a function of dose (p=0.03). These results were not significant when adjusting for multiple comparisons. However, after accounting for multiple comparisons, low IL-2R was associated with improved survival (p<0.05, log-rank). Conclusions: At the time of interim analysis, the MTD has not been reached and study will continue with escalating doses of MM-10-001. The preliminary data indicates potential immunostimulating activity of MM-10-001.