Comparative Genomic Analysis of Intrahepatic Cholangiocarcinoma: Biopsy Type, Ancestry, and Testing Patterns.

BACKGROUND: At diagnosis, the majority of patients with intrahepatic cholangiocarcinoma (IHCC) present with advanced disease and a poor prognosis. Comprehensive genomic profiling (CGP) early in the disease course may increase access to targeted therapies and clinical trials; however, unresolved issues remain surrounding the optimal biopsy type to submit for CGP. PATIENTS AND METHODS: Mutational frequencies between primary tumor biopsies (Pbx), metastatic biopsies (Mbx), and liquid biopsies (Lbx) in 1,632 patients with IHCC were compared. RESULTS: Potentially actionable alterations were found in 52%, 34%, and 35% of patients in the Pbx, Mbx, and Lbx cohorts, respectively. In Pbx, Mbx, and Lbx, FGFR2 rearrangements were found in 9%, 6%, and 4%, and IDH1 mutations were identified in 16%, 5%, and 9% patients, respectively. Moreover, alterations in FGFR2 and IDH1 were significantly associated with distinct ancestries, including 2.1-fold enrichment for FGFR2 rearrangements in patients with African ancestry and 1.5-fold enrichment for IDH1 mutations in patients with admixed American (Hispanic) ancestry. Finally, the publication of biomarker-driven clinical trials in IHCC correlated with changing CGP testing patterns. Significant correlations between patient characteristics and IHCC trial disclosures were observed, including a significant decrease from time between biopsy and CGP testing, and more frequent testing of primary versus metastatic samples. CONCLUSION: Overall, because of the high likelihood of identifying actionable genomic alterations, CGP should be considered for the majority of patients with inoperable IHCC, and Lbx and Mbx can be considered as part of the diagnostic suite. IMPLICATIONS FOR PRACTICE: Comprehensive genomic profiling (CGP) should be considered for all patients with intrahepatic cholangiocarcinoma (IHCC) or suspected IHCC, as actionable alterations were commonly found in multiple genes and a wide variety of FGFR2 fusion partners were identified. The disclosure of IHCC trial data correlated with increased use of CGP, an encouraging trend that moves new therapeutic options forward for rare cancers with a rare biomarker. Although tissue from the primary lesion may identify actionable alterations at higher rates, CGP of a liquid biopsy or metastatic site can be considered, particularly if the primary tissue block is exhausted.

Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial.

Importance: In observational studies, higher plasma 25-hydroxyvitamin D (25[OH]D) levels have been associated with improved survival in metastatic colorectal cancer (CRC). Objective: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with metastatic CRC. Design, Setting, and Participants: Double-blind phase 2 randomized clinical trial of 139 patients with advanced or metastatic CRC conducted at 11 US academic and community cancer centers from March 2012 through November 2016 (database lock: September 2018). Interventions: mFOLFOX6 plus bevacizumab chemotherapy every 2 weeks and either high-dose vitamin D3 (n = 69) or standard-dose vitamin D3 (n = 70) daily until disease progression, intolerable toxicity, or withdrawal of consent. Main Outcomes and Measures: The primary end point was progression-free survival (PFS) assessed by the log-rank test and a supportive Cox proportional hazards model. Testing was 1-sided. Secondary end points included tumor objective response rate (ORR), overall survival (OS), and change in plasma 25(OH)D level. Results: Among 139 patients (mean age, 56 years; 60 [43%] women) who completed or discontinued chemotherapy and vitamin D3 (median follow-up, 22.9 months), the median PFS for high-dose vitamin D3 was 13.0 months (95% CI, 10.1 to 14.7; 49 PFS events) vs 11.0 months (95% CI, 9.5 to 14.0; 62 PFS events) for standard-dose vitamin D3 (log-rank P = .07); multivariable hazard ratio for PFS or death was 0.64 (1-sided 95% CI, 0 to 0.90; P = .02). There were no significant differences between high-dose and standard-dose vitamin D3 for tumor ORR (58% vs 63%, respectively; difference, -5% [95% CI, -20% to 100%], P = .27) or OS (median, 24.3 months vs 24.3 months; log-rank P = .43). The median 25(OH)D level at baseline for high-dose vitamin D3 was 16.1 ng/mL vs 18.7 ng/mL for standard-dose vitamin D3 (difference, -2.6 ng/mL [95% CI, -6.6 to 1.4], P = .30); at first restaging, 32.0 ng/mL vs 18.7 ng/mL (difference, 12.8 ng/mL [95% CI, 9.0 to 16.6], P < .001); at second restaging, 35.2 ng/mL vs 18.5 ng/mL (difference, 16.7 ng/mL [95% CI, 10.9 to 22.5], P < .001); and at treatment discontinuation, 34.8 ng/mL vs 18.7 ng/mL (difference, 16.2 ng/mL [95% CI, 9.9 to 22.4], P < .001). The most common grade 3 and higher adverse events for chemotherapy plus high-dose vs standard-dose vitamin D3 were neutropenia (n = 24 [35%] vs n = 21 [31%], respectively) and hypertension (n = 9 [13%] vs n = 11 [16%]). Conclusions and Relevance: Among patients with metastatic CRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy resulted in a difference in median PFS that was not statistically significant, but with a significantly improved supportive hazard ratio. These findings warrant further evaluation in a larger multicenter randomized clinical trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01516216.

Impact of Medicare Part D on out-of-pocket drug costs and medical use for patients with cancer.

BACKGROUND: Medicare Part D was designed to reduce out-of-pocket (OOP) costs for Medicare beneficiaries, but to the authors' knowledge the extent to which this occurred for patients with cancer has not been measured to date. The objective of the current study was to examine the impact of Medicare Part D eligibility on OOP cost for prescription drugs and use of medical services among patients with cancer. METHODS: Using the Medical Expenditure Panel Survey (MEPS) for the years 2002 through 2010, a differences-in-differences analysis estimated the effects of Medicare Part D eligibility on OOP pharmaceutical costs and medical use. The authors compared per capita OOP cost and use between Medicare beneficiaries (aged ≥65 years) with cancer to near-elderly patients aged 55 years to 64 years with cancer. Statistical weights were used to generate nationally representative estimates. RESULTS: A total of 1878 near-elderly and 4729 individuals with Medicare were included (total of 6607 individuals). The mean OOP pharmaceutical cost for Medicare beneficiaries before the enactment of Part D was $1158 (standard error, ±$52) and decreased to $501 (standard error, ±$30), a decline of 43%. Compared with changes in OOP pharmaceutical costs for nonelderly patients with cancer over the same period, the implementation of Medicare Part D was associated with a further reduction of $356 per person. Medicare Part D appeared to have no significant impact on the use of medications, hospitalizations, or emergency department visits, but was associated with a reduction of 1.55 in outpatient visits. CONCLUSIONS: Medicare D has reduced OOP prescription drug costs and outpatient visits for seniors with cancer beyond trends observed for younger patients, with no major impact on the use of other medical services noted.

Health care disparities in the treatment of colorectal cancer.

OPINION STATEMENT: Treatment of colorectal carcinoma remains challenging, especially in patients with recurrent or metastatic disease. Despite advances in screening and treatment of this cancer, health care disparities remain one of the major yet amendable factors that can lead to differences in outcomes. As clinicians, we need to be aware of such disparities to better tailor our screening and treatment interventions for our patients. Knowing that socioeconomic status, educational status, and personal beliefs contribute to racial disparities in this disease, as clinicians we should strive to know our patients and their beliefs to help minimize this discrepancy. Additionally, we need to maintain and advance our knowledge by keeping up with all clinical and translational research in the field and create strategies to increase enrollment of racial minorities in clinical trials. While conventional chemotherapies continue to play a vital role, it is becoming more and more evident that treatment strategies need to be personalized. Understanding the molecular biology of cancer has changed the landscape of new therapies. Future research needs to be directed towards understanding genetic, biological, and pharmacogenetic and genomic contributors to the development of disease and treatment responses.

Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211).

PURPOSE: Patients with advanced pancreatic neuroendocrine tumors (NETs) have few treatment options that yield objective responses. Retrospective and small prospective studies suggest that capecitabine and temozolomide are associated with high response rates (RRs) and long progression-free survival (PFS). PATIENTS AND METHODS: E2211 was a multicenter, randomized, phase II trial comparing temozolomide versus capecitabine/temozolomide in patients with advanced low-grade or intermediate-grade pancreatic NETs. Key eligibility criteria included progression within the preceding 12 months and no prior temozolomide, dimethyl-triazeno-imidazole-carboxamide or dacarbazine, capecitabine or fluorouracil. The primary end point was PFS; secondary endpoints were overall survival, RR, safety, and methylguanine methyltransferase (MGMT) by immunohistochemistry and promoter methylation. RESULTS: A total of 144 patients were enrolled between April 2013 and March 2016 to temozolomide (n = 72) or capecitabine and temozolomide (n = 72); the primary analysis population included 133 eligible patients. At the scheduled interim analysis in January 2018, the median PFS was 14.4 months for temozolomide versus 22.7 months for capecitabine/temozolomide (hazard ratio = 0.58), which was sufficient to reject the null hypothesis for the primary end point (stratified log-rank P = .022). In the final analysis (May 2021), the median overall survival was 53.8 months for temozolomide and 58.7 months for capecitabine/temozolomide (hazard ratio = 0.82, P = .42). MGMT deficiency was associated with response. CONCLUSION: The combination of capecitabine/temozolomide was associated with a significant improvement in PFS compared with temozolomide alone in patients with advanced pancreatic NETs. The median PFS and RR observed with capecitabine/temozolomide are the highest reported in a randomized study for pancreatic NETs. MGMT deficiency was associated with response, and although routine MGMT testing is not recommended, it can be considered for select patients in need of objective response (ClinicalTrials.gov identifier: NCT01824875).

Concurrent BRAFV600E and BRCA Mutations in MSS Metastatic Colorectal Cancer: Prevalence and Case Series of mCRC patients with prolonged OS.

BACKGROUND: BRAF V600E+ microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients comprise up to 10% of advanced CRC. They have a poor prognosis with a median survival typically <1 year. Despite use of multi-agent 1st line chemotherapy regimens and combination targeted therapies, outcomes are still poor. In our Institutional Molecular Tumor Board (MTB) database, we identified 3 mCRC patients with MSS/BRAF V600E who also had a BRCA1 or BRCA2 co-mutation and had relatively long overall survivals. Prior studies suggested that BRCA mutations are uncommon in CRC and we queried the Foundation Medicine (FM) genomic database to evaluate the prevalence of these cases as well as those with co-mutations in other homologous recombination genes. METHODS: 36,966 CRC pts were sequenced by FMI using hybrid capture comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA) for pathogenic BRAF mutations and/or a mutation in BRCA1/2 or a co-mutation in other homologous recombination (HR) genes (BARD1, CDK12, FANCL, PALB2, ATM, RAD54L, CHEK2, BRAF, BRIP1, RAD51D, RAD51C, RAD51B, CHEK1). Selected cohort analysis of BRAF V600E co-mutated with BRCA1 and BRCA2 were separated into MSI-H and MSS cohorts. The clinicopathological features and genomic loss of heterozygosity (gLOH) of those with a BRAF V600E and a BRCA1/BRCA2 mutation were collected and analyzed. We also describe 3 consecutive cases of mCRC patients, identified through the Inova Schar Cancer Institute (ISCI) MTB registry, whom had prolonged OS. RESULTS: Of 36,966 colorectal cancer pts, 6.6% were BRAF V600E+ and 1.5% had any co-occurring HR gene mutation(s) with 0.6% of the total mCRC population having co-ocurring BRAF V600E and BRCA1/2 alterations. BRCA co-mutations were higher in MSI-High BRAF V600E, however 24.1% of co-occurrences were observed in MSS samples. BRCA1 co-mutation was more commonly associated with MSS BRAF V600E and was associated with a higher gLOH than MSI-H BRAF V600E (18.7% vs 2.8%; p <0.001). In our institutional MTB database, (3/241;1.2%) CRC patients were MSS, BRAF V600E+ with BRCA1 or BRCA2 co-mutations, all somatic in origin, with an average gLOH of 21.4% and overall survivals of 72+(alive), 17+(alive), and 30 months, respectively. CONCLUSION: Co-existence of BRAF V600E/BRCA1/2 may represent a unique subset of advanced MSS CRC that may have a better prognosis and represent an opportunity to test novel targeted therapies. The elevated gLOH in these cases may also be a valuable biomarker for these pts. Larger prospective clinical validation trials in this subset is warranted.

Phase II Trial of the Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma with Tumor Mutation Profiling.

BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is upregulated in nearly half of hepatocellular carcinoma (HCC) tumors and is associated with poor prognosis. In preclinical models of HCC, the combination of mTOR pathway inhibition with the multikinase inhibitor sorafenib improves treatment efficacy. A prior phase I study of the allosteric mTOR inhibitor temsirolimus combined with sorafenib demonstrated acceptable safety at the recommended phase II dose. METHODS: We conducted a single-arm, multicenter phase II trial of the combination of temsirolimus 10 mg intravenously weekly plus sorafenib 200 mg b.i.d. The primary endpoint was time to progression (TTP) with efficacy target of median TTP of at least 6 months; secondary endpoints included overall survival (OS), objective response rate, safety, and alpha-fetoprotein (AFP) tumor marker response. Next-generation tumor sequencing was performed as an exploratory endpoint. RESULTS: Twenty-nine patients were enrolled, including 48% with hepatitis C virus infection and 28% with hepatitis B virus; 86% had Barcelona clinic liver cancer stage C disease. Among 28 patients evaluable for efficacy, the median TTP was 3.7 (95% confidence interval [CI]: 2.2, 5.3) months, with 14% of patients achieving TTP of at least 6 months. The median OS was 8.8 (95% CI: 6.8, 14.8) months. There were no complete or partial responses; 75% of patients had stable disease as best response. AFP decline by at least 50% was associated with prolonged TTP and OS. Serious adverse events occurred in 21%; the most common treatment-related adverse events of CTCAE grade 3 or higher were hypophosphatemia (36%), thrombocytopenia (14%), and rash (11%). There were no grade 5 events attributed to sorafenib or temsirolimus. Tumor next-generation sequencing (NGS) was performed in a subgroup of 24 patients with adequate tumor samples. Tumor mTOR pathway mutations were identified in 42%. There was no association between tumor mutation profile and OS or TTP. CONCLUSIONS: The combination of temsirolimus and sorafenib demonstrated acceptable safety but did not achieve the target threshold for efficacy in this phase II study. Tumor NGS including the presence of mTOR pathway mutations was not associated with treatment response in an exploratory subgroup analysis.

The epothilone B analogue ixabepilone in patients with advanced hepatobiliary cancers: a trial of the University of Chicago Phase II Consortium.

PURPOSE: Hepatobiliary cancers respond poorly to cytotoxic chemotherapy. We evaluated the activity and safety of ixabepilone, an epothilone B analogue which stabilizes microtubules, in a phase II trial in patients with advanced cancers of the gallbladder, bile duct, and liver. METHODS: Eligible patients had previously-untreated, histologically-proven unresectable hepatobiliary cancer. Ixabepilone, 40 mg/m(2), was administered intravenously over 3 h every 21 days. RESULTS: Between January 2002 and April 2005, 54 patients (19 hepatocelluar carcinoma, 13 cholangiocarcinomas, 22 gallbladder carcinomas) were enrolled; 47 patients were evaluable for efficacy. The objective response rate was 8.5%; 51% had stable disease. Median overall survival was 7.0 months (95% CI, 5.0 to 10.8 months) and median progression-free survival was 2.6 months (95% CI, 1.4 to 4.1 months). Grade 3/4 toxicities included neutropenia (39%), fatigue (9%), allergic/hypersensitivity reaction (4%) and sensory neuropathy (4%). CONCLUSION: Single agent ixabepilone has limited activity in advanced hepatobiliary cancers.

A phase II study of sorafenib in advanced uterine carcinoma/carcinosarcoma: a trial of the Chicago, PMH, and California Phase II Consortia.

OBJECTIVES: To determine the efficacy and safety of single agent sorafenib, an oral multi-targeted tyrosine kinase inhibitor, in patients with advanced uterine carcinoma and carcinosarcoma. METHODS: This multi-institutional non-randomized phase II trial enrolled two cohorts: patients with uterine carcinoma (cohort A) and uterine carcinosarcoma (cohort B). Eligibility criteria included measurable disease, 0-1 prior chemotherapy regimens, and ECOG performance status

Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial.

Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D3 (4000 IU) or standard-dose (400 IU) vitamin D3. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks). As compared with standard-dose vitamin D3, high-dose vitamin D3 did not significantly change body weight [-0.7 kg; (95% CI: -3.5, 2.0)], body mass index [-0.2 kg/m2; (95% CI: -1.2, 0.7)], muscle area [-1.7 cm2; (95% CI: -9.6, 6.3)], muscle attenuation [-0.4 HU; (95% CI: -4.2, 3.2)], visceral adipose tissue area [-7.5 cm2; (95% CI: -24.5, 9.6)], or subcutaneous adipose tissue area [-8.3 cm2; (95% CI: -35.5, 18.9)] over the first 8 cycles of chemotherapy. Among patients with advanced or metastatic colorectal cancer, the addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy did not result in any changes in body composition.

Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II Consortia.

OBJECTIVES: The objectives of this phase II trial were to assess the activity and tolerability of the combination of bevacizumab and erlotinib in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer. METHODS: This was a single arm, multicenter phase II trial with overall objective response as the primary endpoint. Eligible patients had two or fewer prior chemotherapy regimens for recurrent or refractory disease and no prior anti-VEGF or anti-EGFR agents. Bevacizumab, 15 mg/kg, was administered intravenously every 21 days and erlotinib, 150 mg orally, was given daily. RESULTS: Between July and October 2005, 13 patients were enrolled. There were two major objective responses, one complete response of 16+ month duration and one partial response of 11 month duration, for a response rate of 15% (95% CI 1.9% to 45.4%). Seven patients had a best response of stable disease. The most common grade 3 or 4 toxicities included anemia (n=1), nausea (n=2), vomiting (n=1), hypertension (n=1), and diarrhea (n=2). One patient with an ileostomy was removed from the study secondary to grade 3 diarrhea. Two patients had fatal gastrointestinal perforations. CONCLUSION: There was no strong suggestion that this combination was superior to single agent bevacizumab, and the rate of gastrointestinal perforation was of concern. The study was therefore stopped. Identification of risk factors for gastrointestinal perforation will be of importance for the use of bevacizumab in the treatment of ovarian cancer.

Do Patients With Advanced Cancer Have the Ability to Make Informed Decisions for Participation in Phase I Clinical Trials?

Purpose Patients with advanced cancer (ACPs) participating in phase I clinical trials inadequately understand many elements of informed consent (IC); however, the prevalence and impact of cognitive impairment has not been described. Patients and Methods ACPs enrolled onto phase I trials underwent neuropsychological assessment to evaluate cognitive functioning (CF) covering the following domains: memory (Hopkins Verbal Learning Test), executive functioning (Trail Making Test B), language (Boston Naming Test-Short Version and Controlled Oral Word Association Test), attention (Trail Making Test A and Wechsler Adult Intelligenence Scale-IV Digit Span), comprehension (Wechsler Adult Intelligence Scale-IV), and quality of life (Functional Assessment of Cancer Therapy-Cognitive Function). Structured interviews evaluated IC and decisional capacity. Psychological measures included distress (Hospital Anxiety Depression Scale) and depression (Beck Depression Inventory-II). Results One hundred eighteen ACPs on phase I trials were evaluated, with CF ranging from mild impairment to superior performance. Only 45% of ACPs recalled physician disclosure of the phase I trial purpose. The 50% of ACPs who correctly identified the phase I research purpose had greater CF compared with ACPs who did not, as revealed by the mean T scores for memory (37.2 ± 5.6 v 32.5 ± 5.1, respectively; P = .001), attention (29 ± 2.7 v 26.9 ± 2.4, respectively; P < .001), visual attention (35.2 ± 6.6 v 31.5 ± 6.2, respectively; P = .001), and executive function (38.9 ± 7.5 v 34 ± 7.1, respectively; P < .001). Older ACPs (≥ 60 years) were less likely to recall physician disclosure of phase I purpose than younger ACPs (30% v 70%, respectively; P = .02) and had measurable deficits in total memory (34.2 ± 5.0 v 37.3 ± 5.6, respectively; P = .002), attention (24.5 ± 2.6 v 28 ± 2.8, respectively; P < .001), and executive function (32.8 ± 7.3 v 36.4 ± 7.6, respectively; P = .01). Older ACPs, compared with younger ACPs, also had greater depression scores (10.6 ± 9.2 v 8.1 ± 5.2, respectively; P = .03) and lower quality-of-life scores (152 ± 29.6 v 167 ± 20, respectively; P = .03). After adjustment by age, no psychological or neuropsychological variable was further significantly associated with likelihood of purpose identification. Conclusion CF seems to play a role in ACP recall and comprehension of IC for early-phase clinical trials, especially among older ACPs.

Targeting Angiogenesis in Colorectal Cancer: Tyrosine Kinase Inhibitors.

Colorectal cancer is commonly diagnosed throughout the world, and treatment options have greatly expanded over the last 2 decades. Targeting angiogenesis has been a major focus of study in a variety of malignancy types. Targeting angiogenesis has been achieved by several mechanisms in colorectal cancer, including use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs). There have been many attempts and failures to prove efficacy of TKIs in the treatment of colorectal cancer including sorafenib, sunitinib, vatalanib, and tivozanib. Regorafenib was the first TKI to demonstrate efficacy and is an orally active inhibitor of angiogenic (including the vascular endothelial growth factor receptors 1, 2, and 3), stromal, and oncogenic receptor tyrosine kinases. There are ongoing investigations of both regorafenib and ninetanib; however, there remains a critical need to better understand novel combinations with TKIs that could prove more efficacious than available options.

Quantitative Sensory Testing at Baseline and During Cycle 1 Oxaliplatin Infusion Detects Subclinical Peripheral Neuropathy and Predicts Clinically Overt Chronic Neuropathy in Gastrointestinal Malignancies.

PURPOSE: Oxaliplatin neurotoxicity has a spectrum of manifestations from an often reversible acute neurotoxicity to a more irreversible "stocking and glove" chronic neuropathy that is associated with high morbidity. Quantitative sensory testing (QST) is a noninvasive psychometric testing method that can potentially be used in the clinic setting to measure subclinical neurologic changes early on to identify patients that will experience chronic oxaliplatin-induced peripheral neuropathy at 1 year. PATIENTS AND METHODS: Thirty patients with gastrointestinal malignancies who were receiving oxaliplatin were recruited. QST and patient-reported outcomes were assessed at baseline; during infusion cycles 1, 2, 4, and 6; and at 1 year. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, chronic neuropathy scores were assessed at the 1-year time point. The variables at each time point were evaluated for prediction of 1-year chronic neuropathy scores. RESULTS: We found that patients with preexisting subclinical neuropathy were more likely to experience grades 2 and 3 chronic neuropathy than were those who did not have this condition (heat detection threshold, Spearman correlation coefficient (rs) = 0.39; P = .037; pellet retrieval time, rs = 0.47; P = .024). Patients in whom thermal and cutaneous sensory deficits developed with cycle 1 infusion were also more likely to experience grades 2 and 3 neuropathy at 1 year (cold detection threshold, rs = 0.50; P = .007; heat detection threshold, rs = 0.39; P = .042; cutaneous detection threshold, rs = 0.42; P = .043). CONCLUSION: QST provides a noninvasive, commercially available, and feasible clinical test to select patients, even before oxaliplatin treatment, who are likely to experience moderate to severe chronic peripheral neuropathy.

Effect of the accountable care act of 2010 on clinical trial insurance coverage.

PURPOSE: The Affordable Care Act (ACA) of 2010 implemented dramatic changes in our health care system. The new law requires that insurers and health plans provide coverage for individuals participating in clinical trials. Currently, there are states that already have laws or agreements requiring clinical trial coverage, but there remain deficiencies that will need to be addressed to achieve compliance with the new law. METHODS: State mandates were reviewed to determine current laws and agreements. The ACA was reviewed to outline its provisions, and these were compared with current mandates to identify deficiencies. RESULTS: Eighteen states meet the requirements set forth by the ACA either through a state law or agreement; 33 states do not meet the requirements. Of these 33 states, 15 do not have any existing laws or agreements in place regarding clinical trials. In states that have deficient policies in place, the most common deficiency is the lack of phase I coverage. The second most common deficiency in policy is coverage of only therapeutic studies. CONCLUSION: Most states currently do not meet the requirements of the ACA and will be required to make changes by 2014. The implications of the ACA with regard to insurance coverage of clinical trials remain unclear as implementation of the legislation unfolds. State governments can take steps to ensure insurance coverage by creating and expanding agreements with insurance companies.

Therapy of locally advanced pancreatic adenocarcinoma: unresectable and borderline patients.

Systemic chemotherapy for advanced pancreatic cancer is commonly used in practice; however, the optimal strategy for both neoadjuvant and adjuvant therapy in this disease remains controversial. A particular challenge remains in patients who are considered to be locally advanced and either unresectable or borderline resectable. Offering optimal neoadjuvant therapy to this group of patients may give them the opportunity to have a curative surgical approach. This article will discuss the potential role of neoadjuvant therapy in borderline, potentially resectable pancreatic cancer. It will also discuss areas of interest in potential targets as the biology of pancreatic adenocarcinoma is further explored.