Concurrent Chemotherapy And Radiation Therapy Research Articles

Follow-Up Imaging Guidelines for Patients with Stage III Unresectable NSCLC: Recommendations Based on the PACIFIC Trial

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Predictors of Financial Toxicity in Patients Receiving Concurrent Radiation and Chemotherapy

<h3>Purpose/Objective(s)</h3> Financial toxicity (FT) is an increasingly recognized concern for cancer patients. We reviewed prospectively collected data to explore factors associated with FT among patients undergoing concurrent chemotherapy and radiation therapy (CRT) within an urban, academic radiation oncology department serving a diverse patient population. <h3>Materials/Methods</h3> The study population was drawn from three prospective trials at our institution of patients receiving concurrent curative-intent CRT. FT was evaluated using weekly EORTC QLQ-C30 questionnaire assessments during the concurrent CRT course. FT was rated on a 4-point Likert scale ranging from experiencing "no" FT to "very much". Patients were classified as having FT if they answered anything other than "no". Rate of change of FT per 30 days was calculated for each patient using linear regression. Those with a rate of increase ≥ 1 point per month were categorized as having treatment-related FT. Chi squared, t test, and logistic were used as appropriate to assess patient demographics, tumor characteristics, and hospitalization as predictors of FT. <h3>Results</h3> 235 patients were included: 32% had head & neck cancer, 29% gastrointestinal primary, 27% lung cancer, 9% cervix cancer, and 4% glioblastoma multiforme. 34% of the study population identified as Black or African American, and 38% identified as Hispanic. On average, patients completed QLQ-C30 5.4 times. Before starting CRT, 52% of patients reported experiencing at least some FT. Higher T stage (<i>P</i> = 0.003) was associated with FT before CRT on bivariate analyses. On multivariate analysis, younger age (OR = 1.06, <i>P</i> = 0.02) was associated with higher FT before CRT after adjusting for age, race, insurance, socioeconomic status, and stage. The mean rate of change in FT was 0.23 points per month. 26% of patients demonstrated treatment-related FT. Experiencing FT before CRT was not associated with treatment-related FT (<i>P</i> = 0.693). Hospitalization during RT (<i>P</i> = 0.015) and cervical cancer diagnosis (<i>P</i> = 0.032) were associated with treatment-related FT. On multivariate analyses, hospitalization (OR 2.92, <i>P</i> = 0.008) was associated with treatment-related FT after adjusting for age, race, insurance, and stage. <h3>Conclusion</h3> Over half of patients reported FT prior to starting CRT. Reassuringly, most patients did not experience a significant increase in FT over the course of concurrent CRT. However, around a quarter of patients did experience treatment-related FT, which was associated with hospitalization during treatment. The finding that patients experience FT prior to CRT start suggests that FT should be evaluated as soon as cancer is diagnosed to allow for early intervention. Further research will help define mechanisms of FT and design interventions to improve FT and avoid hospitalizations.

Unplanned hospital admission in patients receiving concurrent chemotherapy and radiation.

258 Background: Concurrent chemotherapy and radiation therapy (CCRT) has become a curative treatment for many malignancies. Many patients are ultimately cured, but at the cost of significant acute toxicity. When severe, this can require unplanned hospitalization. More research is needed to better identify patients at risk for hospitalization and how to prevent it. Methods: As part of quality improvement at the Seidman Cancer Center, patients in the University Hospitals (UH) system who underwent CCRT were identified. A review was done to determine which patients experienced an unplanned admission in the UH system during their radiation course or within 30 days and the admission diagnosis. We recognized malnutrition and dehydration as causes for hospitalization that were preventable. Several interventions were then performed to reduce these admissions. The first was standardized nutrition screening that prompts earlier dietician referrals for patients at risk of malnutrition. We also instituted hydration assessments for patients beginning in the 3rd week of radiation. Patients found to be dehydrated were scheduled to receive intravenous (IV) fluids as an outpatient for the remainder of their treatment course. Admission rates for patients undergoing CCRT have been tracked as part of this initiative and are reported here. Results: From 7/2017 to 12/2018 we identified 303 patients who completed CCRT. 78 (26%) had an unplanned hospital admission during their treatment course or within 30 days of completing radiation. This included patients with primary head and neck, CNS, GI, lung, GYN, and GU malignancies for which admission rates were 36%, 32%, 23%, 29%, 19% and 8% respectively. 18 (23%) of these patients were admitted after completing the radiation course but within 30 days. The initial admission rate prior to intervention was 34%. This has since declined to 19% (table). Conclusions: Unplanned admission rates are high in patients who undergo CCRT across disease sites. Patients remain at risk following completion of radiation therapy for up to 30 days. Some admissions may be prevented by early dietician referrals and IV hydration. [Table: see text]

Delays in definitive cervical cancer treatment: An analysis of disparities and overall survival impact

ObjectiveDelays in time to treatment initiation (TTI) with definitive radiation therapy (RT) or chemotherapy and RT (CRT) for cervical cancer could lead to poorer outcomes. This study investigates disparities in TTI and the impact of TTI on overall survival (OS). MethodsAdult women with non-metastatic cervical squamous cell carcinoma diagnosed between 2004 and 2014, treated with definitive RT or CRT, and reported to the National Cancer Database were included. TTI was defined as days from diagnosis to start of RT or CRT. The impact of TTI on OS in patients treated with concurrent CRT which included brachytherapy was then assessed. ResultsOverall, 14,924 patients were included (84.7% CRT, 15.3% RT). TTI was significantly longer for Non-Hispanic Black (NHB) (RR, 1.14; 95% CI, 1.11 to 1.18) and Hispanic women (RR, 1.19; 95% CI, 1.15 to 1.24) compared to Non-Hispanic White (NHW) women. Expected TTI (eTTI) for NHW, NHB, and Hispanic women were 38.1, 45.2, and 49.4days. eTTI rose from 36.2days in 2004 to 44.3days by 2014. Intensity-modulated radiation therapy (IMRT) was associated with increased eTTI of 46.5days versus 40.0days for non-IMRT. Longer TTI was not associated with inferior OS in patients treated with concurrent CRT. ConclusionsDelays in starting RT/CRT for cervical cancer increased from 2004 to 2014. Delays disproportionately affect NHB and Hispanic women. However, increased TTI was not associated with increased mortality for women receiving CRT. Further study of TTI's impact on other endpoints is warranted to determine if TTI represents an important quality indicator.

Abstract 36: Changes in cellular and molecular immune markers in the peripheral blood of patients undergoing chemotherapy and radiation for squamous cell carcinoma of head and neck: A prospective pilot study

Abstract Objective: In order to help further development of novel immunotherapeutic targets related to signal-transducer and activator of transcription-3 (STAT3) in squamous cell carcinoma of head and neck (SCCHN), data are needed to help understand changes in immune-mediated signaling during treatment. The purpose of this study was to analyze changes in the mRNA or protein expression of inflammatory or immunosuppressive mediators in peripheral blood mononuclear cells (PBMC) or plasma, in SCCHN patients receiving concurrent chemotherapy and radiation therapy (CRT). Methods: This was a prospective biospecimen collection study of 15 patients with stage III-IV SCCHN who received CRT with curative intent. Blood specimens were obtained before, during weeks 1, 2, 4, 6, and 7 of CRT, and 6-12 weeks after treatment completion. Plasma and PBMC were separated from patients' blood using Vacutainer CPT tubes (BD Bioscience) within 2 hours after collection by centrifugation at 1800×g for 20 min at room temperature and stored in -80°C. Plasma samples were analyzed for 30 human cytokines and chemokines using Luminex FLEXMAP 3D system at the Clinical Immunobiology Correlative Studies (CICSL) core at City of Hope. mRNA was isolated from PBMCs acquired at the baseline and at the second week draw during RT from 6 patients and expression of 730 genes selected for immune profiling was evaluated using nCounter Immune Cell Profiling Assay, and data were analyzed using nSolver software (Nanostring). Results: Among the plasma level of 30 cytokines tested by Luminex Assay, IL-6 showed cumulative increase during RT (one-way ANOVA, p=0.046). At 6 week post RT, IL-6 level decreased comparable to baseline level. Plasma level of IFN-gamma was significantly increased at 2 week of RT and the level remained unchanged until 12 week post CRT (p=0.0004). In contrast, we observed pro-inflammatory cytokine IL-12 was significantly decreased during CRT (p=0.0004). Plasma level of a tumor promoting cytokine HGF was significantly increased during and 12 week post CRT (p=0.0035). Comparison of gene expression profiles in PBMC from 6 patients between baseline and the second week of CRT indicates that mRNA expression of 335 immune-regulators are differentially expressed (p&amp;lt;0.05) among 740 tested. Consistent with the plasma cytokine analysis, mRNA level of IL-6 in PBMC was 13.9 fold increased (p=0.003). Subsequently, increase in STAT3 expression was observed (1.7 fold, p=0.002) since IL-6 stimulates Janus kinase (JAK)-STAT pathway. In addition, mRNA expression of Th2 cytokines including IL-10, IL-5, and TGFb1 were significantly increased by greater than 2 folds (p&amp;lt;0.05). Conclusion: These results suggest CRT affects immune activation in SCCHN patients systemically, which may contribute to immune suppression and disease relapse after treatment. Our data provide an impetus for investigating STAT3-targeted therapies in SCCHN. Citation Format: Sagus Sampath, Hae Jung Won, Ellie Maghami, Erminia Massarelli, Nayana Vora, Lalit Vora, Marcin Kortylewski. Changes in cellular and molecular immune markers in the peripheral blood of patients undergoing chemotherapy and radiation for squamous cell carcinoma of head and neck: A prospective pilot study [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 36.

Rectal Mucinous Adenocarcinoma: MR Imaging Assessment of Response to Concurrent Chemotherapy and Radiation Therapy-A Hypothesis-generating Study.

Purpose To develop a system for assessment of tumor regression grade (TRG) with magnetic resonance (MR) imaging that is applicable to rectal mucinous adenocarcinoma (RMAC) and to obtain a preliminary evaluation of the association of MR imaging assessment of TRG with response to preoperative concurrent chemotherapy and radiation therapy (CCRT). Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. Pre- and post-CCRT MR images of 59 patients with RMAC (median age, 59 years; range, 29-80 years; 42 men [median age, 59 years; range, 36-80 years] and 17 women [median age, 57 years; range, 29-79 years]) who underwent CCRT and subsequent elective resection from July 2005 to June 2015 were analyzed. Two experienced gastrointestinal radiologists independently analyzed imaging parameters such as T stage, mesorectal fascia status, extramural vascular invasion status, and TRG by using modified criteria developed for assessment of RMAC. Interobserver variability was calculated with weighted κ analysis, and disagreement was settled in consensus. MR imaging TRG results were compared with those from pathologic TRG analysis (Mandard grade). Logistic regression analyses were performed to evaluate associations between imaging parameters and pathologic TRG. Results There was moderate to substantial agreement for imaging parameters (post-CCRT T stage-weighted κ, 0.7134; post-CCRT mesorectal fascia status, 0.618; TRG, 0.5023). Modified MR imaging TRG results were significantly associated with pathologic responsiveness (responsive group, Mandard grade 1 or 2; nonresponsive group, Mandard grades 3-5; P = .023). Results of univariate and multivariate logistic regression analyses indicated that MR imaging TRG was the only factor significantly associated with CCRT responsiveness (univariate analysis, P = .023; multivariate analysis, P = .0261). Conclusion The modified MR imaging assessment of TRG was associated with treatment response to CCRT in patients with RMAC. © RSNA, 2017 Online supplemental material is available for this article.

Revisiting Milan cervical cancer study: Do the original findings hold in the era of chemotherapy?

BackgroundThe primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era. MethodsBetween 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical (n=1980) and surgical groups (n=3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort. FindingsAt 46months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p=0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not. InterpretationOur analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era.

Definitive chemotherapy and radiotherapy in patients with stage II non-small cell lung cancer: A population-based outcomes study.

There is a paucity of data on non-surgical outcomes specific to stage II non-small cell lung cancer (NSCLC) patients receiving definitive chemotherapy and radiation therapy (CRT). This study reports population-based outcomes for this subgroup, and investigates a radiation dose-response for overall survival. The National Oncology Data Alliance (NODA), a merging of multiple tumor registries maintained by Elekta(®) medical systems, was queried for stage II patients and CRT. Only curative cases (RT doses ≥59 Gy) were included. Both sequential and concurrent CRT were allowed. Univariate and Cox multivariate techniques were used to assess factors significant for overall survival. These factors included: gender, age, race, radiation dose, radiation total treatment time, stage, histology, tumor size, and chemotherapy sequence. A total of 568 patients were included in the analysis, with a median follow-up of 12.9 months for surviving patients. Patients were treated between 2004 and 2014. Median survival was 20.5 months (95% confidence interval (CI) 18-23 months), with 16% patients alive at 5 years. Only gender was found to be significantly associated with survival in the Cox model. Although median survival was higher in patients receiving greater than 60 Gy (21 months, 95% CI 18-24 moths) compared to 59-60 Gy (16.5 months 95% CI 10-23 months), this was not statistically significant (p=0.6). This is the first report on outcomes for stage II NSCLC patients receiving CRT as definitive therapy. Survival approximates stage III CRT patients from historical phase III trials. As an increasing aging population may parallel a rise in medically inoperable stage II patients, this study can provide useful information when reviewing treatment options.

The role of PET-CT in treatment decision making for women with locally advanced cervical cancer.

5523 Background: Women with locally advanced cervical cancer (LACC) are treated with concurrent chemotherapy and radiation therapy (CRT) with curative intent. Pre-treatment staging is important to ...

A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non-small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.

Stage III Non-Small Cell Lung Cancer Treated Without Concurrent Chemotherapy: What Is the Optimal Radiation Dose?

Based on the preliminary results of RTOG 0617, there may not be an overall survival (OS) benefit for dose escalation beyond 60 Gy in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and radiation therapy (CRT). However, the optimal radiation dose in the absence of concurrent chemotherapy remains unclear. We hypothesized that there may be a benefit for higher radiation doses in the absence of concurrent chemotherapy.

Limited-stage small cell lung cancer treated with cisplatin/irinotecan and concurrent thoracic radiation therapy.

7598 Background: Concurrent chemotherapy and radiation therapy (CRT) is a curative option for limited-stage small cell lung cancer (SCLC). The standard of care in the United States is concurrent etoposide-platinum CRT. In Asia, CRT with irinotecan and cisplatin has been shown to be an effective and tolerable regimen. (Han et al J Clin Oncol 2005 and Jeong et al Lung Cancer 2006) Irinotecan is a potent radiosensitizing agent (Tamura et al Jpn J Cancer Res 1997). Patients with limited-stage SCLC treated with irinotecan-platinum concurrent CRT were identified from our institutional thoracic oncology program database. Methods: 36 patients with limited stage SCLC from 2006-2013 were identified from our database. Ages 49-85. 17 females and 27 males. All patients were treated with cisplatin 30mg/m2 and irinotecan 65mg/m2 on day 1 and 8 every 21 days for a total of 4 cycles, along with concurrent radiation therapy commensurate with cycle 2. 29 patients received BID concurrent radiation therapy (45Gy), and 7 patie...

Final analysis: A randomized, blinded, placebo (P)-controlled phase III study of adjuvant postoperative lapatinib (L) with concurrent chemotherapy and radiation therapy (CH-RT) in high-risk patients with squamous cell carcinoma of the head and neck (SCCHN).

6005 Background: Epidermal growth factor receptor (EGFR) and ErbB2 are overexpressed in up to 90% and 40% of SCCHN, respectively. L, a tyrosine kinase inhibitor (TKI) of both EGFR and ErbB2, demonstrates tumor responses in SCCHN. Methods: Patients with resected stage II-IVA SCCHN, with a surgical margin ≤5mm and/or extracapsular extension were randomized to CT-RT with either P or L. RT was 66Gy (2Gy per day, 5 days per week).100 mg/m2of cisplatin was administered on days 1, 22 and 43 of RT. P or L 1500 mg/day was given for up to one week prior to CT-RT, during CT-RT and for up to 12 months as monotherapy maintenance. Patients were stratified by nodal status, primary tumor location, geographical region and ErbB1 expression. The study had 80% power to detect a 10% absolute difference in disease free survival (DFS) rate (55% to 65%). Results: 688 patients were in the ITT population, 346 L and 342 P. Treatment arms were well balanced for prognostic factors. Median total doses of cisplatin (266.5 and 280 mg/m2...

Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Radiation Therapy and Concomitant Temozolomide: Comparison Study of Standard and High-b-Value Diffusion-weighted Imaging

Purpose To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm2, respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide. Materials and Methods This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm2, and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated. Results In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm2 (ADC1000) and the ADC at b value of 3000 sec/mm2 (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively. Conclusion The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. © RSNA, 2013 Online supplemental material is available for this article.

Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Radiation Therapy and Concomitant Temozolomide: Comparison Study of Standard and High-b-Value Diffusion-weighted Imaging

To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm(2), respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide. This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm(2), and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated. In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm(2) (ADC1000) and the ADC at b value of 3000 sec/mm(2) (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively. The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. Online supplemental material is available for this article.

Percent Change of Perfusion Skewness and Kurtosis: A Potential Imaging Biomarker for Early Treatment Response in Patients with Newly Diagnosed Glioblastomas

To test the predictive value of skewness and kurtosis changes of normalized cerebral blood volume (nCBV) during the early treatment period for differentiating early tumor progression from pseudoprogression in patients with newly diagnosed glioblastomas. The institutional review board approved this retrospective study. The authors assessed 135 patients with newly diagnosed glioblastomas who underwent concurrent chemotherapy and radiation therapy (CCRT) after surgical resection. Patients who developed new or enlarged contrast material-enhanced lesions after CCRT were assessed by means of conventional and perfusion magnetic resonance (MR) imaging. The percent change of skewness and kurtosis on nCBV histograms between the first and second post-CCRT follow-up were classified into four categories. Independent predictors of early tumor progression were determined by means of logistic regression analysis. Of 135 patients, 79 had new or enlarged contrast-enhanced lesions after CCRT, subsequently classified as early tumor progression (n = 42, 53.2%) and pseudoprogression (n = 37, 46.8%). Pseudoprogression was observed in 23 of 24 (95.8%) patients in category 1, 10 of 15 (66.7%) in category 2, four of 20 (20.0%) in category 3, and 0 of 20 (0%) in category 4 (χ(2) test, P < .0001). The histographic pattern of nCBV was the best independent predictor (odds ratio, 3.51; P = .0032) for early tumor progression, rather than each percent change of skewness or kurtosis; the histographic pattern of nCBV represented the largest area under the receiver operating characteristic curve (0.934; 95% confidence interval: 0.855, 0.977), with a sensitivity of 85.7% and a specificity of 89.2%. The percent change of skewness and kurtosis of nCBV may be a potential imaging biomarker for early treatment response in patients with newly diagnosed glioblastomas.

Supportive care needs in newly diagnosed oral cavity cancer patients receiving radiation therapy

This study aimed to examine changes in physical symptom severity, functional status, supportive care needs, and related factors in oral cavity cancer patients during 6 months after beginning radiation therapy (RT) or concurrent chemotherapy and radiation therapy (CCRT). A prospective longitudinal study was conducted involving oral cavity cancer patients from an RT clinic at a medical center in northern Taiwan. Patients were assessed for supportive care needs and physical symptoms at five time points: before the beginning of RT or CCRT and at 1, 2, 3, and 6 months after beginning RT or CCRT. The generalized estimating equation was used to identify predictors of overall needs as well as six specific dimensions of needs. A total of 82 patients completed the 6 months of follow-up. Patients had moderate to high levels of supportive care needs over the 6 months. Although the highest information need was at the pretreatment phase, in general, the peak for overall and individual care needs was at 2 months since first receiving RT or CCRT. Patients without religious beliefs as well as those with higher educational level, functional level, overall physical symptom severity, and baseline anxiety reported more supportive care needs. Anxiety level before treatment was the most common factor across most supportive care needs. Individual physical symptoms, including fatigue, swallowing difficulty, and oral mucositis, were significantly related to higher physical and daily living needs. A systematic clinical assessment to detect patients' care needs is necessary to improve the provision of timely cancer care and meet patients' healthcare needs.

Induction chemotherapy (ICT) containing docetaxel, platinum, and 5 fluorouracil (DPF) regimen in a sequential treatment of locally advanced nasopharyngeal cancer (LANPC): Retrospective analysis from a single institution.

e16037 Background: Concurrent chemotherapy and radiation therapy (CCRT) is the standard treatment of patients (pts) with advanced nasopharyngeal cancer (LANPC). Sequential treatment strategy with ICT helps improve local function, pain control and reduction of systemic failure. We report our limited experience of ICT with DPF regimen in a sequential treatment strategy of patients with LANPC. Methods: The data was recorded following chart review of pts treated for LANPC at the University of Connecticut Health Center between 2004-2010 following approval by the Institutional Review Board. Analysis included age of the pt, stage of the cancer, histological diagnosis; number of ICT cycles, response to treatment as complete disappearance of disease (CR) or more than 50% reduction of the disease (partial response PR), assessed both clinically and with imaging studies. Overall survival (OS) was defined as time from diagnosis to the last follow up, disease free survival (DFS) was defined as time from complete remission of the disease to the last follow up in CR. Results: 5 pts with LANPC were treated sequentially with DPF regimen followed by CCRT. The median age is 55 years, 4 males and one female. All pts had stage IV B, non keratinizing poorly differentiated histology. Average number of DPF ICT was 3. 4 out of 5 pts achieved CR while one pt achieved PR. With a median follow up period of 24 mths, four pts are alive in CR and one pt in PR died of tumor progression. The median DFS in four pts in CR is 16 mths (range 8-70 mths) and overall survival is 24 mths (range 12-74). Conclusion: DPF is well tolerated and effective ICT regimen in patients with LANPC. More studies will help understand the clinical relevance of this regimen as ICT in a sequential treatment of LANP.

Restaging of Rectal Cancer with MR Imaging after Concurrent Chemotherapy and Radiation Therapy

In patients with rectal cancer who have received concurrent chemotherapy and radiation therapy (CCRT) before surgery, magnetic resonance (MR) imaging has low accuracy in prediction of the pathologic stage owing to overstaging or understaging. The factors related to this problem include fibrosis, desmoplastic reaction, edema, inflammation, and viable tumor nets at a fibrotic scar from a previous tumor. Preoperative diagnosis with MR imaging of histologic variants of rectal adenocarcinoma, especially mucinous adenocarcinoma, is important because these variants tend to have a poor response to CCRT. In addition, these variants manifest with high signal intensity on T2-weighted images after CCRT; this finding makes it difficult to differentiate residual tumors from remaining mucin pools. MR volumetry and functional MR imaging may be helpful in prediction and assessment of tumor response to CCRT. Awareness of post-CCRT changes helps radiologists achieve appropriate restaging of irradiated rectal cancer with MR imaging and can lead to a reduction in understaging or overstaging. It is important to obtain and compare both pre- and post-CCRT images before interpreting the post-CCRT images.

Perfusion CT: Noninvasive Surrogate Marker for Stratification of Pancreatic Cancer Response to Concurrent Chemo- and Radiation Therapy

To prospectively determine whether perfusion computed tomography (CT) parameters, such as volume transfer constant (K(trans)) between blood plasma and extracellular extravascular space (EES) and blood volume calculated from dynamic CT data, can be used to predict response of pancreatic cancer to concurrent chemotherapy and radiation therapy (CCRT). This prospective study was institutional review board approved, and written informed consent was obtained. Thirty patients with pancreatic cancer underwent perfusion CT with 64-detector row CT before gemcitabine-based CCRT. Two perfusion parameters (K(trans) and blood volume) measured before treatment were compared between patients who responded to treatment and those who did not, as determined with World Health Organization criteria from first and second posttherapeutic follow-up CT examinations, which were performed at 3- and 6-month follow-up. Statistical analysis was performed with the two-sample t test. A receiver operating characteristic curve was used to determine the best cutoff value of perfusion parameters for differentiation of responders from nonresponders. Twenty of 30 patients examined at 3-month follow-up responded to therapy. Their pretreatment K(trans) value was significantly higher than that of nonresponders (50.8 mL/100 mL/min +/- 30.5 [standard deviation] vs 19.0 mL/100 mL/min +/- 10.8, P = .001). The best cutoff value for differentiating between responders and nonresponders was 31.8 mL/100 mL/min, which yielded 75.0% sensitivity and 90.0% specificity. Ten of 18 patients examined at 6-month follow-up responded to therapy. Their pretreatment K(trans) value was significantly higher than that of nonresponders (58.6 mL/100 mL/min +/- 43.2 vs 19.8 mL/100 mL/min +/- 10.9, P = .002). Responders also had higher blood volume values, but this difference was not significant. Tumors with a high pretreatment K(trans) value tended to respond better to CCRT than did tumors with a low pretreatment K(trans) value. Perfusion CT may be used to predict tumor response to CCRT in patients with pancreatic cancer. This might aid in development of a tailored approach to therapy in these patients.