Phase i study of \u27dose-dense\u27 pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma.

BACKGROUND: This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). METHODS: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m2) q3 weeks × 2 -3 cycles. RESULTS: Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. CONCLUSIONS: Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

<p>Abstract</p> <p>Background</p> <p>This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m². Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m², but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m²) q3 weeks × 2 -3 cycles.</p> <p>Results</p> <p>Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients.</p> <p>Conclusions</p> <p>Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m²with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00330044">NCT00330044</a></p

CogState computerized memory tests in patients with brain metastases: Secondary endpoint results of NRG oncology RTOG 0933

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre-and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests’ completion rates were 52–53% at 2 months and 34–42% at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p B 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p B 0.01). At 4 months, mean relative decline was 7.0% for HVLT-R Delayed Recall and 18.0% for ISLT Delayed Recall. OCLT showed an 8.0% increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z =-0.40, p = 0.34; z =-0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials

Association of pretreatment hippocampal volume with neurocognitive function in patients treated with hippocampal avoidance whole brain radiation therapy for brain metastases: Secondary analysis of NRG Oncology/RTOG 0933

PURPOSE: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933. METHODS AND MATERIALS: Hippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test-Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG 0933(mean 4-month relative decline in HVLT-R DR). Comparisons between patients with deteriorated and nondeteriorated NCF were made using the Wilcoxon test. RESULTS: Forty-two patients were evaluable. The median age was 56.5 years (range, 28-83 years), and 81% had a class II recursive partitioning analysis. The median total, right, and left HVs were 5.4 cm CONCLUSIONS: Larger HV was positively associated with improved performance on baseline and 4-month HVLT-R TR and DR scores in patients with brain metastases undergoing hippocampal-avoidant whole brain radiation therapy but was not associated with a change in NCF

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PROCTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

Purpose—To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials—Patients enrolled in Trial XXXX (XXXX) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly x4 during treatment; 12-weeks post-treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results—Among 226 study sites participating in Trial XXXX, 100% completed 35-minute PROCTCAE training for clinical research associates (CRAs); 80 sites enrolled patients of which 34 (43%) required tablet computers to be provided. All 152 patients in Trial XXXX agreed to selfreport using the PRO-CTCAE (median age 66; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range 30–240), and median time for CRAs to teach a patient to self-report was 10 minutes (range 2–60). Compliance was high, particularly during active treatment when patients self-reported at 86% of expected time points, although compliance was lower post-treatment (72%). Common reasons for non-compliance were institutional errors such as forgetting to provide computers to participants; patients missing clinic visits; internet connectivity; and patients feeling “too sick”. Conclusions—Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic adverse events at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between-visits, and by employing central compliance monitoring. These approaches are being incorporated into ongoing studies

Photon irradiation using a water bath technique for treatment of confluent carcinoma in situ of the hand, digits, and nail bed: a case report

Abstract Background Confluent squamous cell carcinoma in situ, or Bowen’s disease, involving the hand, digit, and nail bed is rare and represents a significant therapeutic challenge. Surgical excision is recommended as first-line treatment but in cases of extensive disease can lead to unacceptable functional morbidity or cosmetic outcomes. Radiation therapy has been shown to be equally efficacious to surgery in the treatment of carcinoma in situ but its use has historically been limited due to concerns regarding toxicity. In this case report we present a novel therapeutic technique that may enable radiotherapy to be employed as a definitive treatment option in these challenging cases. Case presentation A 75-year-old white man with a previous history of carcinoma in situ of his right hand previously treated with 5-fluorouracil presented with recurrent biopsy-proven confluent squamous cell carcinoma in situ of multiple surfaces of his right hand and digits with involvement of nail beds. To avoid extensive resection and possible amputation he was offered definitive external beam radiation therapy utilizing a water bath as a tissue-equivalent bolus material. This protocol enabled improved dose homogeneity to the target volume while minimizing acute toxicity. He experienced complete clinical resolution of the disease with only minimal acute edema and hyperpigmentation. Twenty months following treatment completion he remains disease-free with normal function and excellent cosmesis. Conclusions Therapeutic radiation utilizing water as a tissue-equivalent bolus in this complicated case enabled definitive treatment of disease without compromising functional or cosmetic outcomes. Radiotherapy may therefore be an alternative and under-utilized approach to surgical excision in difficult-to-treat cases of carcinoma in situ

Radiation therapy of recurrent anal squamous cell carcinoma in-situ: a case report

<p>Abstract</p> <p>Introduction</p> <p>High-grade anal intraepithelial neoplasia, also referred to as anal squamous carcinoma in-situ, or Bowen's disease of the anus, make up less than 1% of all digestive system cancers in the United States. The treatment of choice is surgical resection with anal mapping. However, this disease often recurs or persists, requiring additional surgery for these patients. This can compromise the anal sphincter leading to leakage. In this case report, we discuss the efficacy of radiation therapy as a modality to treat post-excisional recurrent Bowen's disease, which may prevent sphincter compromise, leading to improved quality of life.</p> <p>Case presentation</p> <p>An 84-year-old Caucasian woman presented with post-excisional persistent/recurrent squamous cell carcinoma in-situ. The initial lesion measured 3 cm in diameter on the right lateral side of the anal margin. A standard surgery consisting of wide local excision with anal mapping was performed. The margins were clear and our patient was followed up. Our patient recurred with a 1.2 × 0.8 cm lesion on the left anal verge extending to the anal canal. A biopsy along with mapping was done, and 2 of the 17 mapping specimens were positive for carcinoma in-situ, one in the anal canal. Due to the location of the positive anal mapping, and in order to prevent sphincter compromise on re-excision, our patient was offered definitive radiation therapy. Two years after radiation therapy, our patient showed no signs of recurrent disease and had good sphincter control.</p> <p>Conclusion</p> <p>Although the main treatment modality for treating persistent/recurrent Bowen's disease is surgery, an alternative approach using external beam radiation for CIS may be enough to provide a cure for some patients with recurrent disease.</p