Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study.

BACKGROUND: In the primary analysis of the CLEAR study, lenvatinib plus pembrolizumab significantly improved progression-free survival and overall survival versus sunitinib in patients with advanced renal cell carcinoma (data cutoff Aug 28, 2020). We aimed to assess overall survival based on 7 months of additional follow-up. METHODS: This is a protocol-prespecified updated overall survival analysis (data cutoff March 31, 2021) of the open-label, phase 3, randomised CLEAR trial. Patients with clear-cell advanced renal cell carcinoma who had not received any systemic anticancer therapy for renal cell carcinoma, including anti-vascular endothelial growth factor therapy, or any systemic investigational anticancer drug, were eligible for inclusion from 200 sites (hospitals and cancer centres) across 20 countries. Patients were randomly assigned (1:1:1) to receive lenvatinib (20 mg per day orally in 21-day cycles) plus pembrolizumab (200 mg intravenously every 21 days; lenvatinib plus pembrolizumab group), lenvatinib (18 mg per day orally) plus everolimus (5 mg per day orally; lenvatinib plus everolimus group [not reported in this updated analysis]) in 21-day cycles, or sunitinib (50 mg per day orally, 4 weeks on and 2 weeks off; sunitinib group). Eligible patients were at least 18 years old with a Karnofsky performance status of 70 or higher. A computer-generated randomisation scheme was used, and stratification factors were geographical region and Memorial Sloan Kettering Cancer Center prognostic groups. The primary endpoint was progression-free survival assessed by independent imaging review according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). In this Article, extended follow-up analyses for progression-free survival and protocol-specified updated overall survival data are reported for the intention-to-treat population. No safety analyses were done at this follow-up. This study is closed to new participants and is registered with ClinicalTrials.gov, NCT02811861. FINDINGS: Between Oct 13, 2016, and July 24, 2019, 1417 patients were screened for inclusion in the CLEAR trial, of whom 1069 (75%; 273 [26%] female, 796 [74%] male; median age 62 years [IQR 55-69]) were randomly assigned: 355 (33%) patients (255 [72%] male and 100 [28%] female) to the lenvatinib plus pembrolizumab group, 357 (33%) patients (275 [77%] male and 82 [23%] female) to the sunitinib group, and 357 (33%) patients to the lenvatinib plus everolimus group (not reported in this updated analysis). Median follow-up for progression-free survival was 27·8 months (IQR 20·3-33·8) in the lenvatinib plus pembrolizumab group and 19·4 months (5·5-32·5) in the sunitinib group. Median progression-free survival was 23·3 months (95% CI 20·8-27·7) in the lenvatinib plus pembrolizumab group and 9·2 months (6·0-11·0) in the sunitinib group (stratified hazard ratio [HR] 0·42 [95% CI 0·34-0·52]). Median overall survival follow-up was 33·7 months (IQR 27·4-36·9) in the lenvatinib plus pembrolizumab group and 33·4 months (26·7-36·8) in the sunitinib group. Overall survival was improved with lenvatinib plus pembrolizumab (median not reached [95% CI 41·5-not estimable]) versus sunitinib (median not reached [38·4-not estimable]; HR 0·72 [95% CI 0·55-0·93]). INTERPRETATION: Efficacy benefits of lenvatinib plus pembrolizumab over sunitinib were durable and clinically meaningful with extended follow-up. These results support the use of lenvatinib plus pembrolizumab as a first-line therapy for patients with advanced renal cell carcinoma. FUNDING: Eisai and Merck Sharp & Dohme.

Chaperonin containing TCP1 as a marker for identification of circulating tumor cells in blood.

Herein we report the use of Chaperonin-Containing TCP-1 (CCT or TRiC) as a marker to detect circulating tumor cells (CTCs) that are shed from tumors during oncogenesis. Most detection methods used in liquid biopsy approaches for enumeration of CTCs from blood, employ epithelial markers like cytokeratin (CK). However, such markers provide little information on the potential of these shed tumor cells, which are normally short-lived, to seed metastatic sites. To identify a marker that could go beyond enumeration and provide actionable data on CTCs, we evaluated CCT. CCT is a protein-folding complex composed of eight subunits. Previously, we found that expression of the second subunit (CCT2 or CCTß) inversely correlated with cancer patient survival and was essential for tumorigenesis in mice, driving tumor-promoting processes like proliferation and anchorage-independent growth. In this study, we examined CCT2 expression in cancer compared to normal tissues and found statistically significant increases in tumors. Because not all blood samples from cancer patients contain detectable CTCs, we used the approach of spiking a known number of cancer cells into blood from healthy donors to test a liquid biopsy approach using CCT2 to distinguish rare cancer cells from the large number of non-cancer cells in blood. Using a clinically validated method for capturing CTCs, we evaluated detection of intracellular CCT2 staining for visualization of breast cancer and small cell lung (SCLC) cancer cells. We demonstrated that CCT2 staining could be incorporated into a CTC capture and staining protocol, providing biologically relevant information to improve detection of cancer cells shed in blood. These results were confirmed with a pilot study of blood from SCLC patients. Our studies demonstrate that detection of CCT2 could identify rare cancer cells in blood and has application in liquid biopsy approaches to enhance the use of minimally invasive methods for cancer diagnosis.

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study.

BACKGROUND: In the Mammary Oncology Assessment of LEE011's (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR+/HER2- advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2. PATIENTS AND METHODS: Postmenopausal women with HR+/HER2- ABC without previous treatment for advanced disease were randomized (1:1) to ribociclib 600 mg/d (3 weeks on/1 week off) with letrozole 2.5 mg/d (continuous) or placebo with letrozole. The primary end point was locally assessed PFS. RESULTS: Overall, 213 US patients were enrolled in MONALEESA-2 (ribociclib, n = 100; placebo, n = 113). Baseline characteristics were similar between treatment groups and consistent with the global population. With a median follow-up of 27 months, 38 (38%) and 29 (26%) patients in the ribociclib and placebo groups, respectively, had continued to receive treatment. Median PFS was 27.6 months with ribociclib and 15.0 months with placebo (hazard ratio, 0.53). The most common all-cause adverse events were neutropenia (ribociclib, 72.0% [n = 72]; placebo, 4.6% [n = 5]), nausea (ribociclib, 69.0% [n = 69]; placebo, 44.0% [n = 48]), and fatigue (ribociclib, 60.0% [n = 60]; placebo, 50.5% [n = 55]). Two patients (ribociclib, 2.0%; placebo, 0%) experienced febrile neutropenia. CONCLUSION: In the US subset of MONALEESA-2, ribociclib with letrozole showed superior efficacy versus letrozole alone. These findings are consistent with the global population and support first-line use of ribociclib with letrozole in patients with HR+/HER2- ABC.

Dipeptidyl Peptidase-4 Inhibition May Stimulate Progression of Carcinoid Tumor.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as saxagliptin, have gained a rapid growth in use in the treatment of type 2 diabetes mellitus in the past decade. Although they are considered to have a good safety profile, controversy exists regarding their potential to stimulate neoplasm growth. We report here a patient with metastatic carcinoid tumor. His disease was stable for several years with plasma serotonin level (which was used to monitor disease progression) in 700-800 ng/mL range. After initiation of treatment with saxagliptin, however, his serotonin level almost doubled (1358 ng/mL), concerning progression of the disease. After discontinuation of saxagliptin, serotonin level returned to baseline quickly, while other laboratory markers, such as complete blood count (CBC), comprehensive metabolic profile (CMP) with liver function tests (LFTs), and lactate dehydrogenase (LD), remained unchanged before, during, and after the treatment with saxagliptin. This temporal correlation suggests a possible interaction between the activity of carcinoid tumors and the use of DPP-4 inhibitors. Although we were not able to find any literature providing a direct evidence that saxagliptin alters progression of the carcinoid tumors, we recommend alternative management for the treatment of diabetes in patients with carcinoid or other neuroendocrine tumors.

Use of Adjuvant Cisplatin-Based Versus Carboplatin-Based Chemotherapy in Non-Small-Cell Lung Cancer: Findings From the Florida Initiative for Quality Cancer Care.

PURPOSE: For patients with resected non-small-cell lung cancer, national guidelines recommend cisplatin-based doublet chemotherapy as the preferred treatment. However, many patients receive a carboplatin-based regimen instead. We aimed to identify factors associated with use of a cisplatin-based regimen and explore its association with other quality-of-care measures. METHODS: This analysis was part of the Florida Initiative for Quality Cancer Care, an audit and feedback project among 11 medical oncology practices. Feedback-sharing sessions based on findings of year 2006 took place in 2008. Eligible patients were random samples of those with resected stage I to III non-small-cell lung cancer treated in 2006 and 2009. RESULTS: In both years combined, 81 patients received adjuvant platinum-based doublets: 33 patients (41%) received cisplatin, and 48 patients (59%) received carboplatin. Use of a cisplatin-based doublet significantly increased in 2009 compared with 2006, from 24% to 56% (P = .006). Multivariable analysis determined that academic practices used cisplatin more frequently than nonacademic practices (odds ratios, 3.26; 95% CI, 1.19 to 8.91; P = .02). Moreover, patients treated in 2009 were more likely to receive cisplatin than those treated in 2006 (odds ratio, 4.89; 95% CI, 1.75 to 13.67; P = .002). No significant association between use of cisplatin and other quality-of-care measures was found. CONCLUSION: In this study, academic practice status and treatment year predicted use of adjuvant cisplatin-based chemotherapy. The increase in use of cisplatin in 2009, as compared with 2006, suggests that audit and feedback may be effective ways to promote such use.

Florida Initiative for Quality Cancer Care: Changes in Psychosocial Quality of Care Indicators Over a 3-Year Interval.

PURPOSE: Identifying and addressing psychosocial concerns is increasingly recognized as an important aspect of cancer care that needs to be improved. As part of the Florida Initiative for Quality Cancer Care, medical record reviews were conducted to evaluate cancer care, including psychosocial care, at oncology practices in Florida in 2006. Results were subsequently disseminated to the practices, and performance was reassessed at the same practices in 2009. METHODS: Data were available for patients with colorectal, breast, and non-small-cell lung cancer first seen by a medical oncologist in 2006 (n = 1,609) and 2009 (n = 1,720) at the same 10 practice sites. Performance on each psychosocial indicator was evaluated for overall change over time and for variability in change based on practice site and cancer type. RESULTS: The percentage of patients identified as having a problem in emotional well-being increased significantly over time, from 24% to 31% among those assessed (P = .002) and from 13% to 16% overall (P = .026). In contrast, there no significant changes over time in assessment of emotional well-being (53% to 51%, P = .661) or in action taken to address problems (57% to 45%, P = .098). CONCLUSION: Findings suggest more intensive efforts than audit and feedback will be required to improve the quality of psychosocial care and that greater recognition of problems with emotional well-being may tax the ability of practices to link patients with appropriate services. Systematic research is needed to identify and disseminate effective strategies for implementing routine assessment of well-being and addressing the increased demands for care this will generate.

Nanoparticle albumin-bound-Paclitaxel in the treatment of metastatic urethral adenocarcinoma: the significance of molecular profiling and targeted therapy.

Primary urethral cancer is rare and accounts for only 0.003% of all malignancies arising from the female genitourinary tract. Due to the rarity of this disease, no consensus exists regarding the optimal therapeutic approach. Nanoparticle albumin-bound-paclitaxel has been shown to be effective in the treatment of a number of malignancies including metastatic breast, pancreatic, and bladder cancer. We present a 67-year-old woman with advanced metastatic urethral adenocarcinoma resistant to two lines of chemotherapy (ifosfamide/paclitaxel/cisplatin and irinotecan/5-fluorouracil/leucovorin) that showed a dramatic response to nanoparticle albumin-bound-paclitaxel. This is the first case report to document the use and efficacy of nanoparticle albumin-bound-paclitaxel in the treatment of unresectable metastatic urethral cancer.

Florida Initiative for Quality Cancer Care: improvements in breast cancer quality indicators during a 3-year interval.

BACKGROUND: The Florida Initiative for Quality Cancer Care (FIQCC), composed of 11 practice sites across Florida, conducted its initial evaluation of adherence to breast cancer quality of care indicators (QCI) in 2006, with feedback provided to encourage quality improvement efforts at participating sites. In this study, our objective was to reassess changes over time resulting from these efforts. STUDY DESIGN: Quality care indicators were derived from the Quality Oncology Practice Initiative, the National Comprehensive Cancer Network, the American College of Surgeons, and expert panel consensus. Medical records were reviewed for breast cancer patients first seen by medical oncologists in 2009 at the FIQCC sites, using the same performance indicators as in 2006. Statistical comparisons of 2006 vs 2009 data across sites were made by Pearson chi-square exact test using Monte Carlo estimation. RESULTS: Charts of 602 patients in 2006 and 636 patients in 2009 were compared. Performance on medical oncology QCI improved over time for documentation of clinical trial participation discussion (p = 0.001), documentation of consent for chemotherapy (p = 0.047), definitive surgery done after neoadjuvant chemotherapy (p = 0.017), and planned dose of chemotherapy consistent with published regimens (p = 0.02). Improvements in surgical QCI were seen for documentation of specimen orientation (p < 0.001), inking of margins (p < 0.0001), and performance of sentinel lymph node biopsy (p = 0.035). CONCLUSIONS: The 2006 FIQCC study identified several medical and surgical oncology QCI improvement needs. Quality improvement efforts resulted in better performance for numerous metrics, therefore speaking to the benefits of reassessment of adherence to performance indicators to guide QCI efforts.

Changes in the care of non-small-cell lung cancer after audit and feedback: the Florida initiative for quality cancer care.

PURPOSE: Audit and feedback have been widely used to enhance the performance of various medical practices. Non-small-cell lung cancer (NSCLC) is one of the most common diseases encountered in medical oncology practice. We investigated the use of audit and feedback to improve the care of NSCLC. METHODS: Medical records were reviewed for patients with NSCLC first seen by a medical oncologist in 2006 (n = 518) and 2009 (n = 573) at 10 oncology practices participating in the Florida Initiative for Quality Cancer Care. In 2008, feedback from 2006 audit results was provided to practices, which then independently undertook steps to improve their performance. Sixteen quality-of-care indicators (QCIs) were evaluated on both time points and were examined for changes in adherence over time. RESULTS: A statistically significant increase in adherence was observed for five of 16 QCIs. Adherence to brain staging using magnetic resonance imaging or computed tomography scan for stage III NSCLC (57.8% in 2006 v 82.8% in 2009; P = .001), availability of chemotherapy flow sheet (89.2% v 97.0%; P < .001), documentation of performance status for stage III and IV disease (43.4% v 51.3%; P < .001), availability of pathology report for patients undergoing surgery (95.2% v 99.2%; P = .02), and availability of signed chemotherapy consent (69.5% v 76.3%; P = .04). There were no statistically significant decreases in adherence on any QCIs. CONCLUSION: Audit with feedback was associated with a modest but important improvement in the treatment of NSCLC. Whether these changes are durable will require long-term follow-up.

Etirinotecan pegol: development of a novel conjugated topoisomerase I inhibitor.

Irinotecan is a very active chemotherapeutic agent used for the treatment of several malignancies, including colorectal cancer, gastroesophageal tumors, lung cancer, breast cancer, ovarian cancer, and primary brain tumors. Irinotecan exerts its antineoplastic effects through its active metabolite 7-ethyl-10-hydroxycamptothecin. This metabolite is also responsible for the classic side effects associated with irinotecan that include diarrhea and neutropenia. A pegylated form of this agent, etirinotecan pegol, is undergoing clinical development with the main goal of increasing its therapeutic efficacy and its safety. This agent decreases the maximal exposure to 7-ethyl-10-hydroxycamptothecin while providing continuous exposure to the treated tumor. The half-life of etirinotecan pegol is 50 days and it has been studied in different schedules: weekly, every other week, and once every 3 weeks. The maximum tolerated dose of etirinotecan pegol was found to be 145 mg/m(2). There have already been two phase II clinical trials published showing the efficacy of this novel agent in the treatment of metastatic ovarian and breast cancer. The side effect profile was acceptable for most patients, with a number of patients experiencing diarrhea and even neutropenia.

Florida Initiative for Quality Cancer Care: improvements on colorectal cancer quality of care indicators during a 3-year interval.

BACKGROUND: The quality of cancer care has become a national priority; however, there are few ongoing efforts to assist medical oncology practices in identifying areas for improvement. The Florida Initiative for Quality Cancer Care is a consortium of 11 medical oncology practices that evaluates the quality of cancer care across Florida. Within this practice-based system of self-assessment, we determined adherence to colorectal cancer quality of care indicators (QCIs) in 2006, disseminated results to each practice and reassessed adherence in 2009. The current report focuses on evaluating the direction and magnitude of change in adherence to QCIs for colorectal cancer patients between the 2 assessments. STUDY DESIGN: Medical records were reviewed for all colorectal cancer patients seen by a medical oncologist in 2006 (n = 489) and 2009 (n = 511) at 10 participating practices. Thirty-five indicators were evaluated individually and changes in QCI adherence over time and by site were examined. RESULTS: Significant improvements were noted from 2006 to 2009, with large gains in surgical/pathological QCIs (eg, documenting rectal radial margin status, lymphovascular invasion, and the review of ≥ 12 lymph nodes) and medical oncology QCIs (documenting planned treatment regimen and providing recommended neoadjuvant regimens). Documentation of perineural invasion and radial margins significantly improved; however, adherence remained low (47% and 71%, respectively). There was significant variability in adherence for some QCIs across institutions at follow-up. CONCLUSIONS: The Florida Initiative for Quality Cancer Care practices conducted self-directed quality-improvement efforts during a 3-year interval and overall adherence to QCIs improved. However, adherence remained low for several indicators, suggesting that organized improvement efforts might be needed for QCIs that remained consistently low over time. Findings demonstrate how efforts such as the Florida Initiative for Quality Cancer Care are useful for evaluating and improving the quality of cancer care at a regional level.

A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors.

PURPOSE: This study was designed to establish the maximum tolerated dose (MTD) and to evaluate tolerability, pharmacokinetics, and antitumor activity of etirinotecan pegol. EXPERIMENTAL DESIGN: Patients with refractory solid malignancies were enrolled and assigned to escalating-dose cohorts. Patients received 1 infusion of etirinotecan pegol weekly 3 times every 4 weeks (w × 3q4w), or every 14 days (q14d), or every 21 days (q21d), with MTD as the primary end point using a standard 3 + 3 design. RESULTS: Seventy-six patients were entered onto 3 dosing schedules (58-245 mg/m(2)). The MTD was 115 mg/m(2) for the w × 3q4w schedule and 145 mg/m(2) for both the q14d and q21d schedules. Most adverse events related to study drug were gastrointestinal disorders and were more frequent at higher doses of etirinotecan pegol. Late onset diarrhea was observed in some patients, the frequency of which generally correlated with dose density. Cholinergic diarrhea commonly seen with irinotecan treatment did not occur in patients treated with etirinotecan pegol. Etirinotecan pegol administration resulted in sustained and controlled systemic exposure to SN-38, which had a mean half-life of approximately 50 days. Overall, the pharmacokinetics of etirinotecan pegol are predictable and do not require complex dosing adjustments. Confirmed partial responses were observed in 8 patients with breast, colon, lung (small and squamous cell), bladder, cervical, and neuroendocrine cancer. CONCLUSION: Etirinotecan pegol showed substantial antitumor activity in patients with various solid tumors and a somewhat different safety profile compared with the irinotecan historical profile. The MTD recommended for phase II clinical trials is 145 mg/m(2) q14d or q21d.

Evaluating the quality of colorectal cancer care in the state of Florida: results from the Florida Initiative for Quality Cancer Care.

PURPOSE: The Florida Initiative for Quality Cancer Care (FIQCC) was established to evaluate the quality of cancer care at the regional level across the state of Florida. This study assessed adherence to validated quality indicators in colorectal cancer (CRC) and the variability in adherence by practice site, volume, and patient age. METHODS: The FIQCC is a consortium of 11 medical oncology practices in Florida. Medical record reviews were conducted for 507 patients diagnosed with CRC and seen as new medical oncology patients in 2006. Thirty-five indicators were evaluated individually and categorized across clinical domains and components of care. RESULTS: The mean adherence for 19 of 35 individual indicators was > 85%. Pathology reports were compliant on reporting depth of tumor invasion (96%; range, 86% to 100%), grade (93%; range, 72% to 100%), and status of proximal and distal surgical resection margins (97%; range. 86% to 100%); however, documentation of lymphovascular and perineural invasion did not meet adherence standards (76%; range, 53% to 100% and 39%; range, 5% to 83%, respectively). Among patients with nonmetastatic rectal cancer, documentation of the status of surgical radial margins was consistently low across sites (42%; range, 0% to 100%; P = .19). Documentation of planned treatment regimens for adjuvant chemotherapy was noted in only 58% of eligible patients. CONCLUSION: In this large regional initiative, we found high levels of adherence to more than half of the established quality indicators. Although the quality of care delivered within FIQCC practices seems to be high, several components of care were identified that warrant further scrutiny on both a systemic level and at individual centers.

Degree of variability in performance on breast cancer quality indicators: findings from the Florida initiative for quality cancer care.

PURPOSE: The Florida Initiative for Quality Cancer Care (FIQCC) comprises 11 Florida practice sites that participate in comprehensive reviews of quality of care specific to patients with cancer. Here, we examined site adherence to performance indicators to assess quality of care for patients with breast cancer (BC). METHODS: Quality indicators were scripted on the basis of accepted guidelines from the Quality Oncology Practice Initiative, National Comprehensive Cancer Network, American College of Surgeons, and site-specific expert panel consensus. Comprehensive chart reviews, including both medical and surgical oncology quality measures, were conducted for patients with BC first seen in 2006 by a medical oncologist at one of the sites. Statistical comparisons were made by the Pearson χ(2) exact test, using Monte Carlo estimation. RESULTS: Charts of 622 patients were reviewed. Of the 34 indicators, seven for medical oncology and four for surgical oncology fell below the 85% level of adherence. A statistically significant difference (P < .001) in variation of performance across the sites was found for the following medical and surgical oncology indicators: documentation of menopausal status, family history, informed consent, planned chemotherapy regimen and flow sheet, American Joint Committee on Cancer staging, HER2/neu status, reporting of margin orientation and inking of the margins, histological grade, having a sentinel lymph node biopsy for invasive BC, and obtaining a mammogram within 14 months of definitive surgery. CONCLUSION: The FIQCC has identified how multiple aspects of BC care can be improved. Findings are being used at the participating institutions to guide quality improvement efforts.

Evaluating the quality of psychosocial care in outpatient medical oncology settings using performance indicators.

OBJECTIVE: An American Psychosocial Oncology Society workgroup has developed indicators of the quality of psychosocial care that can be measured through review of medical records. The present report describes the first large-scale use of these indicators to evaluate psychosocial care in outpatient medical oncology settings. METHODS: Medical records of 1660 colorectal, breast and non-small cell cancer patients first seen by a medical oncologist in 2006 at 11 practice sites in Florida were reviewed for performance on indicators of the quality of psychosocial care. RESULTS: Assessment of emotional well-being was significantly less likely to be documented than assessment of pain (52 vs 87%, p<0.001). A problem with emotional well-being was documented in 13% of records and evidence of action taken was documented in 58% of these records. Ten of eleven practice sites performed below an 85% threshold on each indicator of psychosocial care. Variability in assessment of emotional-well being was associated (p<0.02) with practice site and patient gender and age while variability in assessment of pain was associated (p<0.001) with practice site and cancer type. CONCLUSIONS: Findings illustrate how use of the psychosocial care indicators permits identification of specific practice sites and processes of care that should be targeted for quality improvement efforts. Additionally, findings demonstrate the extent to which routine assessment of emotional well-being lags behind routine assessment of pain in cancer patients.

Quality of care in non-small-cell lung cancer: findings from 11 oncology practices in Florida.

BACKGROUND: Limited data on the quality of care in non-small-cell lung cancer (NSCLC) are available. This study aims to assess the quality of care in NSCLC among 11 medical oncology practices in Florida and to explore the impact of practice volume on care. METHODS: Clinical guidelines and existing indicators were reviewed, and an expert survey was conducted to identify a set of process-based quality of care indicators (QI). Medical records of new patients with NSCLC seen in 2006 were retrospectively reviewed for the adherence to these QIs. RESULTS: We reviewed the compliance with a set of 11 QIs (four general and seven NSCLC specific) among 531 patients. The patient median age was 68 years; 51% were male, and 49% had advanced NSCLC. The median adherence rates to general QIs and NSCLC-specific QIs were 95% (range 69% to 99%) and 69% (range 29% to 91%), respectively. We identified three main areas of deficiencies: chemotherapy consenting (69%), brain staging for stage III NSCLC (59%), and performance status assessment for advanced stages (42%). Significant variation in the adherence rates across practice sites was observed in five of 11 QIs. CONCLUSION: On the basis of this data set of participating institutions in Florida, several areas in the care of patients with NSCLC were identified as targets for future quality improvement efforts.

Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer.

PURPOSE: Amrubicin is a synthetic anthracycline with potent topoisomerase II inhibition. This phase II study was conducted to confirm safety and activity of amrubicin in the treatment of refractory small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with refractory SCLC (either with progressive disease as best response or progression within 90 days of first-line therapy) received amrubicin (40 mg/m(2)/d for 3 every 21 days). The primary end point was overall response rate (ORR); secondary end points included progression-free survival (PFS), overall survival (OS), and change in left ventricular ejection fraction (LVEF). RESULTS: Seventy-five patients with a median progression-free interval after first-line therapy of 38 days were enrolled; 69 patients received a median of four amrubicin cycles (range, one to 12 cycles). The ORR was 21.3% (95% CI, 12.7% to 32.3%), with one complete response (1.3%) and 15 partial responses (20%). Median PFS and OS were 3.2 months (95% CI, 2.4 to 4.0 months) and 6.0 months (95% CI, 4.8 to 7.1 months), respectively. The ORR in 43 patients who never responded to first-line therapy was 16.3% (95% CI, 6.8% to 30.7%). Most commonly reported grade 3 or 4 adverse events included neutropenia (67%), thrombocytopenia (41%), and anemia (30%), with febrile neutropenia in 12%. There was no decrease in mean LVEF with cumulative amrubicin doses exceeding 750 mg/m(2). CONCLUSION: Single-agent amrubicin showed promising activity with a 21.3% ORR and an acceptable safety profile when used as second-line therapy patients with platinum-refractory SCLC. Amrubicin did not induce early cardiotoxicity, but its long-term effects are unknown.

Initial evaluation of quality indicators for psychosocial care of adults with cancer.

BACKGROUND: The American Psychosocial Oncology Society has developed the first indicators of the quality of psychosocial care for cancer patients. This report describes the initial evaluation of these indicators. METHODS: Medical records of 388 colorectal cancer patients first seen by a medical oncologist in 2006 at seven practice sites were reviewed by trained abstractors whose accuracy was documented by periodic checks. RESULTS: Rates of assessment of emotional well-being within 1 month of a patient's first visit with a medical oncologist ranged from 6% to 84% (mean = 60%; P < .001). Among the 45 patients identified as having a problem with emotional well-being, rates of evidence of action taken (or explanation for no action) ranged from 0% to 100% (mean = 51%; P = .85). A direct comparison showed that pain was assessed more often than emotional well-being in these patients (87% vs 60%, P < .001). CONCLUSIONS: Findings show these indicators can be measured easily and reliably, demonstrate variability across practices that suggests potential for improvement, and yield information that can be used to take actions to improve quality. Additional findings suggest that, to date, efforts to promote routine symptom assessment have been more successful for pain than for emotional well-being.

MAL is expressed in a subset of Hodgkin lymphoma and identifies a population of patients with poor prognosis.

Classical Hodgkin lymphoma (cHL) and mediastinal (thymic) large B-cell lymphoma (MLBL) have clinical, histopathologic, and molecular genetic similarities. MAL, a gene that encodes a protein associated with lipid rafts in T and epithelial cells, is overexpressed in a majority of MLBLs and has been reported in a minority of cHLs. To study the clinical significance of MAL in cHL, we immunostained 86 cases; 16 cHLs (19%) expressed MAL. Expression correlated with nodular sclerosis subtype, and within this subtype, with grade 2 histology. Univariable analysis revealed association of age of 45 years or older, MAL expression, and an International Prognostic Score of more than 2 with worse failure-free survival. Age of 45 years or older, MAL expression, and stage III or IV were associated with worse overall survival (OS). Cox proportional hazards modeling showed age (P = .04 and P = .03, respectively) and MAL expression (P = .03 and P = .01, respectively) as independent predictors of time to failure-free survival and OS. Stage showed borderline significance in OS (P = .08). MAL expression seems to identify a subset of cHL with an adverse outcome and provides additional evidence for a link between cHL and MLBL.

Expression of bcl-2 in classical Hodgkin's lymphoma: an independent predictor of poor outcome.

PURPOSE: Although most classical Hodgkin's lymphoma (CHL) patients are cured, a significant minority fails primary therapy and may die as a result of their disease. Age, stage, and other basic clinical and laboratory parameters, which comprise the International Prognostic Score (IPS), are used at diagnosis to predict outcome. To date, there is no consensus on biologic markers that add value to these parameters. PATIENTS AND METHODS: We evaluated 107 CHL patients for bcl-2, p53, and p21 expression by immunohistochemistry using tissue microarrays and correlated the results with outcome. The median follow-up of the 79 surviving patients was 6.8 years. RESULTS: Univariate analysis showed that age > or = 45 years, stage III or IV, and IPS > or = 3 were associated with a poor failure-free survival (FFS) and overall survival (OS). bcl-2 was expressed in 26% of patients and was associated with poor FFS and a trend for OS. p53 expression in combination with lack of p21 expression was not associated with outcome. Multivariate analysis showed that three factors were independently associated with both FFS and OS: age > or = 45 years, stage III or IV, and bcl-2 expression. Using these three parameters, a scoring system was devised that stratified patients into three risk groups (with zero, one, or two to three of these risk factors) and a progressively worse FFS and OS (P < .001). CONCLUSION: Expression of bcl-2 in CHL is a useful, independent prognostic marker and can be used in association with clinical parameters to identify newly diagnosed patients with a good, intermediate, or poor prognosis.