Safety of Early Discharge for Low-Risk Patients With Febrile Neutropenia: A Multicenter Randomized Controlled Trial

Febrile neutropenia commonly complicates cancer chemotherapy. Outpatient treatment may reduce costs and improve patient comfort but risk progression of undetected medical problems

Patient‐reported outcomes after 3‐dimensional conformal, intensity‐modulated, or proton beam radiotherapy for localized prostate cancer

BACKGROUND: Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3‐dimensional conformal radiotherapy (3DCRT), intensity‐modulated radiotherapy (IMRT), or proton beam therapy (PBT). METHODS: The authors reviewed patient‐reported outcomes data collected prospectively using validated instruments that assessed bowel and urinary quality of life (QOL) for patients with localized prostate cancer who received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful differences in mean QOL scores were defined as those exceeding half the standard deviation of the baseline mean value. Changes from baseline were compared within groups at the first post‐treatment follow‐up (2‐3 months from the start of treatment) and at 12 months and 24 months. RESULTS: At the first post‐treatment follow‐up, patients who received 3DCRT and IMRT, but not those who received PBT, reported a clinically meaningful decrement in bowel QOL. At 12 months and 24 months, all 3 cohorts reported clinically meaningful decrements in bowel QOL. Patients who received IMRT reported clinically meaningful decrements in the domains of urinary irritation/obstruction and incontinence at the first post‐treatment follow‐up. At 12 months, patients who received PBT, but not those who received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary irritation/obstruction domain. At 24 months, none of the 3 cohorts reported clinically meaningful changes in urinary QOL. CONCLUSIONS: Patients who received 3DCRT, IMRT, or PBT reported distinct patterns of treatment‐related QOL. Although the timing of toxicity varied between the cohorts, patients reported similar modest QOL decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months. Prospective randomized trials are needed to further examine these differences. Cancer 2013. © 2013 American Cancer Society. Prostate cancer patients who receive 3‐dimensional conformal radiotherapy, intensity‐modulated radiotherapy, or proton beam therapy report distinct patterns of treatment‐related quality of life. Although the timing of toxicity varies between cohorts, patients report similar modest quality‐of‐life decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97476/1/27956_ftp.pd

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy – characterized by some benefit but only rare durable responses – was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC. Additionally, durvalumab following chemoradiation has been approved for use in patients with locally advanced disease. Due to the distinct features of cancer immunotherapy, and rapid progress in the field, clinical guidance is needed on the use of these agents, including appropriate patient selection, sequencing of therapies, response monitoring, adverse event management, and biomarker testing. The Society for Immunotherapy of Cancer (SITC) convened an expert Task Force charged with developing consensus recommendations on these key issues. Following a systematic process as outlined by the National Academy of Medicine, a literature search and panel voting were used to rate the strength of evidence for each recommendation. This consensus statement provides evidence-based recommendations to help clinicians integrate immune checkpoint inhibitors into the treatment plan for patients with NSCLC. This guidance will be updated following relevant advances in the field

Design considerations in a sib-pair study of linkage for susceptibility loci in cancer

<p>Abstract</p> <p>Background</p> <p>Modern approaches to identifying new genes associated with disease allow very fine analysis of associaton and can be performed in population based case-control studies. However, the sibpair design is still valuable because it requires few assumptions other than acceptably high penetrance to identify genetic loci.</p> <p>Methods</p> <p>We conducted simulation studies to assess the impact of design factors on relative efficiency for a linkage study of colorectal cancer. We considered two test statistics, one comparing the mean IBD probability in affected pairs to its null value of 0.5, and one comparing the mean IBD probabilities between affected and discordant pairs. We varied numbers of parents available, numbers of affected and unaffected siblings, reconstructing the genotype of an unavailable affected sibling by a spouse and offspring, and elimination of sibships where the proband carries a mutation at another locus.</p> <p>Results</p> <p>Power and efficiency were most affected by the number of affected sibs, the number of sib pairs genotyped, and the risk attributable to linked and unlinked loci. Genotyping unaffected siblings added little power for low penetrance models, but improved validity of tests when there was genetic heterogeneity and for multipoint testing. The efficiency of the concordant-only test was nearly always better than the concordant-discordant test. Replacement of an unavailable affected sibling by a spouse and offspring recovered some linkage information, particularly if several offspring were available. In multipoint analysis, the concordant-only test was showed a small anticonservative bias at 5 cM, while the multipoint concordant-discordant test was generally the most powerful test, and was not biased away from the null at 5 cM.</p> <p>Conclusion</p> <p>Genotyping parents and unaffected siblings is useful for detecting genotyping errors and if allele frequencies are uncertain. If adequate allele frequency data are available, we suggest a single-point affecteds-only analysis for an initial scan, followed by a multipoint analysis of affected and unaffected members of all available sibships with additional markers around initial hits.</p

Quantitative Clinical Staging for Patients With Malignant Pleural Mesothelioma

Abstract Background: Analysis of the International Association for the Study of Lung Cancer (IASLC) Malignant Pleural Mesothelioma (MPM) database revealed that clinical (cTNM) staging minimally stratified survival and was discrepant with pathological (pTNM) staging. To improve prognostic classification of MPM, alternative staging models based on quantitative parameters were explored. Methods: An institutional review board–approved MPM registry was queried to identify patients with available pathological and preoperative imaging data. Qualifying patients were randomly assigned to training and test sets in a 1:2 ratio. Computed cTNM and pTNM staging (AJCC Cancer Staging Manual, 7th ed.) were compared. Quantitative image analysis included tumor volume assessed from three-dimensional reconstruction of computed tomography scans (VolCT) and maximal fissural thickness (Fmax). Survival was estimated using the Kaplan-Meier method, and the relationship with VolCT was examined by Cox regression analysis to identify optimized cut-points. Performance of cTNM and quantitative models derived was compared in the test set using Harrell’s C index. Results: A total of 472 patients met inclusion criteria. TNM staging was concordant with pathological TNM staging in 171 of 472 (36.2%), understaged in 209 (44.2%), and overstaged in 92 (19.4%) patients. The most concordant feature was involvement of interlobar fissures. A quantitative clinical staging model comprising VolCT and Fmax (c-index = 0.638, 95% confidence interval [CI] = 0.603 to 0.673) performed statistically significantly better as a prognostic classifier when compared in the test set with cTNM (c-index = 0.562, 95% CI = 0.525 to 0.599, P = .001). Conclusions: Improved prognostic performance may be achievable by quantitative clinical staging combining VolCT and Fmax, providing a cost-effective and clinically relevant surrogate for clinical TNM stage

Effect of sample size and varying recombination fraction on estimated power

<p><b>Copyright information:</b></p><p>Taken from "Design considerations in a sib-pair study of linkage for susceptibility loci in cancer"</p><p>http://www.biomedcentral.com/1471-2350/9/64</p><p>BMC Medical Genetics 2008;9():64-64.</p><p>Published online 10 Jul 2008</p><p>PMCID:PMC2488325.</p><p></p

Effect of sample size and varying attributable risk at the unlinked locus on estimated power

<p><b>Copyright information:</b></p><p>Taken from "Design considerations in a sib-pair study of linkage for susceptibility loci in cancer"</p><p>http://www.biomedcentral.com/1471-2350/9/64</p><p>BMC Medical Genetics 2008;9():64-64.</p><p>Published online 10 Jul 2008</p><p>PMCID:PMC2488325.</p><p></p

Effect of sample size and varying attributable risk at the linked locus on estimated power

<p><b>Copyright information:</b></p><p>Taken from "Design considerations in a sib-pair study of linkage for susceptibility loci in cancer"</p><p>http://www.biomedcentral.com/1471-2350/9/64</p><p>BMC Medical Genetics 2008;9():64-64.</p><p>Published online 10 Jul 2008</p><p>PMCID:PMC2488325.</p><p></p

Clinical indications and results after chest wall resection for recurrent mesothelioma

ObjectiveThe ipsilateral hemithorax is the most common site of recurrence after surgical resection for malignant pleural mesothelioma. Salvage treatment has generally been ineffective. We reviewed the outcomes after resection of isolated ipsilateral chest recurrence after cytoreductive surgery in patients with malignant pleural mesothelioma.MethodsPatients with malignant pleural mesothelioma who underwent initial surgical resection at our institution from 1988 to 2011 and were subsequently treated for localized recurrence with an additional chest resection were identified and their data retrospectively reviewed.ResultsA total of 1142 patients underwent either extrapleural pneumonectomy (n = 794) or pleurectomy/decortication (n = 348). Of the patients who returned for follow-up, 47 (4.1%) had chest wall recurrence amenable to resection. The location of recurrence was predominantly incisional (49%) and/or costophrenic (38%). The median time to recurrence after either extrapleural pneumonectomy or pleurectomy/decortication was 16.1 months (range, 2.7-58.2). No 30-day mortality was found for chest wall resection, and the median length of stay in the hospital was 3 days (range, 0-12). The median overall survival duration after chest wall resection correlated positively with the time to recurrence (epithelial: median, 8.9, 17.2, and 35.8 months for a time to recurrence of <12, 12 to <24, and ≥24 months, respectively; biphasic: median, 2.7 and 15.9 months for a time to recurrence of <10 and ≥10 months, respectively).ConclusionsChest wall resection is a safe and effective therapeutic option in the management of localized chest wall recurrence of malignant pleural mesothelioma. The time to recurrence appears to be predictive of the expected survival benefit in both epithelial and biphasic malignant pleural mesothelioma