Ritsuko Komaki - Academia.edu (original) (raw)
Papers by Ritsuko Komaki
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To demonstrate that high-resolution computed tomography (CT) can be used to quantify los... more Purpose: To demonstrate that high-resolution computed tomography (CT) can be used to quantify loss of pulmonary compliance in irradiated mice. Methods and Materials: Computed tomography images of three nonirradiated (controls) and three irradiated mice were obtained 200 days after a single dose of 16-Gy Co (60) thoracic irradiation. While intubated, each animal was imaged at static breath-hold pressures of 2, 10, and 18 cm H 2 O. A deformable image registration algorithm was used to calculate changes in air volume between adjacent-pressure CT image pairs (e.g., 2 and 10 cm H 2 O), and functional images of pulmonary compliance were generated. The mass-specific compliance was calculated as the change in volume divided by the pressure difference between the 2 image sets and the mass of lung tissue. Results: For the irradiated mice, the lung parenchyma mean CT values ranged from ؊314 (؎ 11) Hounsfield units (HU) to ؊378 (؎ 11) HU. For the control mice, the mean CT values ranged from ؊549 (؎ 11) HU to ؊633 (؎ 11) HU. Irradiated mice had a 60% (45, 74%; 95% confidence interval) lower mass-specific compliance than did the controls (0.039 [؎ 0.0038] vs. 0.106 [؎ 0.0038] mL air per cm H 2 O per g lung) from the 2-cm to 10-cm H 2 O CT image pair. The difference in compliance between groups was less pronounced at the higher distending pressures. Conclusion: High-resolution CT was used to quantify a reduction in mass-specific compliance following whole lung irradiation in mice. This small animal radiation injury model and assay may be useful in the study of lung injury.
The Lancet Oncology, 2015
Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobe... more Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials.
Radiotherapy and Oncology, 2015
We report long-term disease control, survival, and toxicity for patients with locally advanced no... more We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study. All patients received passive-scatter proton therapy, planned with 4D-CT-based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). The 134 patients (21 stage II, 113 stage III; median age 69years) had a median gross tumor volume (GTV) of 70cm(3) (range, 5-753cm(3)); 77 patients (57%) received 74Gy(RBE), and 57 (42%) received 60-72Gy(RBE) (range, 60-74.1Gy(RBE)). At a median follow-up time of 4.7years, median OS times were 40.4months (stage II) and 30.4months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity.
Journal of the National Comprehensive Cancer Network : JNCCN, 2014
Current algorithms for surveillance of patients with esophageal adenocarcinoma (EAC) after chemor... more Current algorithms for surveillance of patients with esophageal adenocarcinoma (EAC) after chemoradiation and surgery (trimodality therapy [TMT]) remain empiric. The authors hypothesized that the frequency, type, and timing of relapses after TMT would be highly associated with surgical pathology stage (SPS), and therefore SPS could be used to individualize the surveillance strategy. Between 2000 and 2010, 518 patients with EAC were identified who underwent TMT at The University of Texas MD Anderson Cancer Center and were frequently surveyed. Frequency, type, and timing of the first relapse (locoregional and/or distant) were tabulated according to SPS. Standard statistical approaches were used. The median follow-up time after esophageal surgery was 55.4 months (range, 1.0-149.2 months). Disease relapse occurred in 215 patients (41.5%). Higher SPS was associated with a higher rate of relapse (0/I vs II/III, P≤.001; 0/I vs II, P=.002; SPS 0/I vs III, P≤.001; and SPS II vs III, P=.005) ...
Journal of Clinical Oncology, 2014
Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimoda... more Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimodality therapy [BMT]) experience frequent relapses. In a large cohort, we assessed the timing, frequency, and types of relapses during an aggressive surveillance program and the value of the salvage strategies. Patients with EC (N = 276) who received BMT were analyzed. Patients who had surgery within 6 months of chemoradiotherapy were excluded to reduce bias. We focused on local relapse (LR) and distant metastases (DM) and the salvage treatment of patients with LR only. Standard statistical methods were applied. The median follow-up time was 54.3 months (95% CI, 48.4 to 62.4). First relapses included LR only in 23.2% (n = 64), DM with or without LR in 43.5% (n = 120), and no relapses in 33.3% (n = 92) of patients. Final relapses included no relapses in 33.3%, LR only in 14.5%, DM only in 15.9%, and DM plus LR in 36.2% of patients. Ninety-one percent of LRs occurred within 2 years and 98% occurred within 3 years of BMT. Twenty-three (36%) of 64 patients with LR only underwent salvage surgery, and their median overall survival was 58.6 months (95% CI, 28.8 to not reached) compared with those patients with LR only who were unable to undergo surgery (9.5 months; 95% CI, 7.8 to 13.3). Unlike in patients undergoing trimodality therapy, for whom surveillance/salvage treatment plays a lesser role,(1) in the BMT population, approximately 8% of all patients (or 36% of patients with LR only) with LRs occurring more than 6 months after chemoradiotherapy can undergo salvage treatment, and their survival is excellent. Our data support vigilant surveillance, at least in the first 24 months after chemotherapy, in these patients.
Lung Cancer, 2003
Results: The study was well balanced between the two treatment arms in terms on age, sex, KPS and... more Results: The study was well balanced between the two treatment arms in terms on age, sex, KPS and distribution of metastasis. The second line chemotherapy used in patients of GV arm was carboplatin. No statistically significant difference was observed in overall survival (GV vs CGV) (median 275 vs 300 days; 1 year survival 26 vs 28%; p: 0.8) as well as in progression free survival (median 150 vs 175 days; p: 0.4). The objective response rates were 40% for GV and 48% for CGV (p: 0.4). Pts in CGV had more haematological and non-haematological toxicity including the only toxic death registered in this study. Major toxicity grade 3-4 registered were (GV vs CGV; %); Anaemia (23 vs 38;~: 0.04) neutropenia (26 vs 48; p: 0.004); plaquetopenia (2 vs 14; p:O.Oi) and neuropathy (4 vs 22; p: 0.007. Thrombocytosis was registered in 58% and 35% of pts treated with GV and CGV respectively which was associated with a thrombotic episode in 14% of cases in both arms. Dose reduction and/or delay of schedule of treatment were made in 60% and 73% of pts in GV and CGV arm respectively.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014
MicroRNAs (miRNAs) are small, highly conserved non-coding RNAs that regulate many biological proc... more MicroRNAs (miRNAs) are small, highly conserved non-coding RNAs that regulate many biological processes. We sought to investigate whether three serum miRNAs related to immunity or inflammation were associated with esophagitis induced by chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). We measured serum miR-155, miR-221 and miR-21, before and during week 1-2 of CRT for 101 NSCLC patients by real-time PCR. Associations between miRNA and severe radiation-induced esophageal toxicity (RIET) were analyzed by logistic regression. We found that patients with stage IIIB-IV disease, higher mean esophagus dose or esophageal V50 had higher rates of severe RIET. Furthermore, high levels of miR-155 and miR-221 at week 1-2 of CRT were also risk factors for severe RIET (miR-155: OR=1.53, 95% CI: 1.04-2.25, P=0.03; miR-221: OR=2.07, 95% CI: 1.17-3.64, P=0.012). In addition, the fold change of miR-221 was also predictive of severe RIET (OR=1.18, 95% CI: 1.02-1.37, P=0.026). However...
Practical radiation oncology
To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the... more To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the United States. A survey of 36 questions was designed to collect information regarding practice patterns of radiation oncologists for the management of patients with NSCLC. All American Society for Radiation Oncology members were invited to respond. Four hundred twenty-four responses from radiation oncologists in the United States were received. The response rate for the survey was approximately 20%. Substantial discrepancies were seen in the use of stereotactic body radiation therapy (SBRT) for patients with peripherally and centrally located early-stage tumors and in the recommended SBRT dose. There was a near consensus opinion regarding the use of concurrent chemotherapy and the radiation dose for patients with inoperable stage II and III NSCLC with a good performance status; however, in patients with a poor performance status or in patients with stage IV disease treatment recommendat...
American Journal of Clinical Oncology-cancer Clinical Trials, 1985
Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirm... more Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirmed inoperable or unresectable carcinoma of the lung of all cell types were treated with curative intent. Forty-five patients lived a minimum of 3 years and 32 patients lived 5 or more years. The 3-year survival rate increased from 7.6% (15/197) between January, 1971 and June, 1975 to 14.1% (30/213) for the interval from July, 1975 to August, 1978 (p less than 0.01). Factors associated with long-term survival were performance status (p less than 0.01), early stage (p less than 0.001), high total dose of radiation (p less than 0.02), large cell carcinoma (p less than 0.01), inoperable for medical reasons (p less than 0.001), and thoracotomy to determine unresectability (p less than 0.04). The difference in survival rates between the two time periods was not related to different patient factors. Survival rates were most improved in the second time period for patients with Stage II or Stage III carcinoma of the lung. Eight patients died from cancer between 36 and 54 months of initial treatment. Five patients died of intercurrent disease without evidence of cancer of the lung after 3 years. An increasing proportion of long-term survivors of inoperable carcinoma of the lung can be expected to result from a better understanding of these diseases, more technically sophisticated external irradiation, and the use of combination chemotherapy for small cell carcinoma.
Journal of Thoracic Oncology, 2008
We investigated the value of lung perfusion imaging in predicting the risk of developing pulmonar... more We investigated the value of lung perfusion imaging in predicting the risk of developing pulmonary complications after chemoradiation (CRT) or radiation therapy (RT) for lung cancer. Fifty patients who underwent lung perfusion imaging before RT for lung cancer were included. Planar and single photon emission computed tomography/computed tomography images of the lungs were obtained. Lung perfusion score (LPS) was developed to visually grade localized perfusion defect per lung on a scale of 0 to 4 and perfusion pattern in the remaining lungs on a scale of 1 to 4. The LPS is the sum of the score for the localized perfusion defect in each lung plus the score for the remaining lungs perfusion. LPSs were correlated with pulmonary function tests and the patients were followed for 8 months after therapy to determine the incidence of grade 2 to 5 symptomatic therapy related pulmonary complications according to the common terminology criteria for adverse events (CTCAE 3.0). Thirty-four patients underwent CRT and 16 underwent RT. The mean total radiation dose delivered was 56.1 +/- 10.4 Gy. Eighteen patients (36%) suffered from pulmonary complications at a mean interval of 3.4 months after therapy. Nine patients had grade 2, 7 had grade 3, 1 had grade 4, and 1 had grade 5 pulmonary complications. The mean LPS was 4.9 in patients who developed pulmonary complications versus 3.5 in patients who did not (p = 0.01). There were no significant difference between pulmonary function tests in the patients with pulmonary complications and the patient without. In addition, there were no significant differences between the mean lung radiation dose, the volume of lung irradiated or the percentage of lung receiving greater than 20 Gy between the two groups. LPS using lung perfusion imaging is useful for predicting possible pulmonary complications after CRT or RT in lung cancer patients.
New England Journal of Medicine, 1999
For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic ... more For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001). Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.
Nature Medicine, 1996
A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was ... more A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was produced to mediate transfer of wild-type p53 into human non-small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector-related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector-p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.
Lung Cancer, 2005
In LD-SCLC, combined modality therapy has emerged as the standard of practice in good performance... more In LD-SCLC, combined modality therapy has emerged as the standard of practice in good performance status (PS) patients (pts). Pignon&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s meta-analysis [N Engl J Med 1992;327:1618-24] showed that combination chemotherapy (CT) and thoracic radiation (XRT) in LD-SCLC yielded an absolute 5.4% increase in 3-year survival versus chemotherapy alone. Concurrent chemoradiation upfront has generated the highest survival rates [Murray. J Clin Oncol 1993;11:336-44; Jeremic. J Clin Oncol 1996;15:893-900; Takada. J Clin Oncol 2002;20:3054-60]. In stage III NSCLC, multiple studies have shown therapeutic superiority for combination chemotherapy and XRT versus RT alone; and recent literature suggests a therapeutic advantage for concurrent chemoradiation versus chemotherapy followed by XRT [Curran. ASCO 2000;19:484a; Furuse. JCO 1999;17:2692-9; Zatloukal. ASCO 2002;A-1159]. Data are less secure regarding the role of chemotherapy in stage I and II NSCLC. A stratified two-step cluster sampling technique was used for data collection. Five hundred and forty-one individuals diagnosed between 1998 and 1999 with lung cancer, either LD-SCLC or stages I-III NSCLC were sampled from 58 institutions featuring radiotherapy facilities, giving a weighted sample size (wss) of 42,335 patients. All pts had Karnofski performance status (KPS) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=60. We determined the percentage who received chemotherapy; the nature of chemotherapy and its timing with respect to XRT. SUDAAN statistical software was used to allow the incorporation of the design elements and weights to reflect the relative contribution of each institution and each patient in the analysis Of 72 (wss=6138) pts with LD-SCLC, 100% received XRT and 95% received chemotherapy (CT); 66% received concurrent (con) CT and XRT, of whom 29% also received CT pre XRT; 22% received CT post XRT as well, and 23% received both: 63% received sequential CT--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;XRT+/-con CT; and 38% received some CT after XRT. Fifty-two percent received cisplatin (DDP), and 38% received carboplatin (CBDCA); 73% received etoposide (VP-16), while 10% received paclitaxel. Of 469 pts (wss=36,197) with NSCLC, 52% received CT, including 30% with stage I disease, 48% with stage II NSCLC, 60% with stage III NSCLC, and 50% with unknown stage. Thirty-nine percent received sequential CT--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;XRT+/-CT, of whom 49% received CT pre XRT only. Seventy-four percent received con CT and XRT; and 27% received posterior CT, of whom 84% also received con CT/XRT. Forty-five received some CT in the pre-op setting and 15% in the post-op setting. Twelve percent received DDP-based therapy, while only 13% and 7% received VP-16 or vincas, respectively; 67% received CBDCA. Seventy-two percent received taxanes, of whom 96% received paclitaxel. Gemcitabine was administered to 3% of NSCLC pts. Combined modality therapy is typically employed in the therapy of LD-SCLC and LA-NSCLC. The majority of those treated for SCLC receive concurrent CT/XRT, while nearly 3/4 of those treated with CT and XRT for LA-NSCLC received concurrent CT/XRT. Current practice in the US generally matches evidence-based literature, although a significant percentage of practitioners substitute CBDCA for DDP in both venues and use paclitaxel in lieu of vincas or etoposide in NSCLC.
Lung Cancer, 2004
Unresectable;
International Journal of Radiation Oncology*Biology*Physics, 2014
Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We ass... more Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received !60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade !3 or grade !2 RP. Median lung volume receiving !20 Gy (V 20 ) was 31%, and post-RT WBC counts ranged from 1.7 to 21.2 Â 10 3 WBCs/mL. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursivepartitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade !3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 Â 10 3 /mL for grade !3 and !2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade !3 (nZ46, ORZ2.6, 95% confidence interval [CI] 1.4-4.9, PZ.003) and grade !2 RP (nZ164, ORZ2.0, 95% CI 1.2-3.4, PZ.01). This association held in a stepwise multivariate regression. Of note, V 20 was found to be significantly associated with grade !2 RP (ORZ2.2, 95% CI 1.2-3.4, PZ.01) and trended toward significance for grade !3 RP (ORZ1.9, 95% CI 1.0-3.5, PZ.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity. Ó
International Journal of Radiation Oncology*Biology*Physics, 2006
To assess the association of clinical and especially dosimetric factors with the incidence of pos... more To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy) was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V(dose) and absolute V(dose)), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS(dose)). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V(dose) or VS(dose)) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving…
International Journal of Radiation Oncology*Biology*Physics, 2007
To investigate the ability of four-dimensional computed tomography (4D CT)-derived ventilation im... more To investigate the ability of four-dimensional computed tomography (4D CT)-derived ventilation images to identify regions of highly functional lung for avoidance in intensitymodulated radiotherapy (IMRT) planning in locally advanced non-small cell lung cancer (NSCLC).
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To demonstrate that high-resolution computed tomography (CT) can be used to quantify los... more Purpose: To demonstrate that high-resolution computed tomography (CT) can be used to quantify loss of pulmonary compliance in irradiated mice. Methods and Materials: Computed tomography images of three nonirradiated (controls) and three irradiated mice were obtained 200 days after a single dose of 16-Gy Co (60) thoracic irradiation. While intubated, each animal was imaged at static breath-hold pressures of 2, 10, and 18 cm H 2 O. A deformable image registration algorithm was used to calculate changes in air volume between adjacent-pressure CT image pairs (e.g., 2 and 10 cm H 2 O), and functional images of pulmonary compliance were generated. The mass-specific compliance was calculated as the change in volume divided by the pressure difference between the 2 image sets and the mass of lung tissue. Results: For the irradiated mice, the lung parenchyma mean CT values ranged from ؊314 (؎ 11) Hounsfield units (HU) to ؊378 (؎ 11) HU. For the control mice, the mean CT values ranged from ؊549 (؎ 11) HU to ؊633 (؎ 11) HU. Irradiated mice had a 60% (45, 74%; 95% confidence interval) lower mass-specific compliance than did the controls (0.039 [؎ 0.0038] vs. 0.106 [؎ 0.0038] mL air per cm H 2 O per g lung) from the 2-cm to 10-cm H 2 O CT image pair. The difference in compliance between groups was less pronounced at the higher distending pressures. Conclusion: High-resolution CT was used to quantify a reduction in mass-specific compliance following whole lung irradiation in mice. This small animal radiation injury model and assay may be useful in the study of lung injury.
The Lancet Oncology, 2015
Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobe... more Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials.
Radiotherapy and Oncology, 2015
We report long-term disease control, survival, and toxicity for patients with locally advanced no... more We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study. All patients received passive-scatter proton therapy, planned with 4D-CT-based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). The 134 patients (21 stage II, 113 stage III; median age 69years) had a median gross tumor volume (GTV) of 70cm(3) (range, 5-753cm(3)); 77 patients (57%) received 74Gy(RBE), and 57 (42%) received 60-72Gy(RBE) (range, 60-74.1Gy(RBE)). At a median follow-up time of 4.7years, median OS times were 40.4months (stage II) and 30.4months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity.
Journal of the National Comprehensive Cancer Network : JNCCN, 2014
Current algorithms for surveillance of patients with esophageal adenocarcinoma (EAC) after chemor... more Current algorithms for surveillance of patients with esophageal adenocarcinoma (EAC) after chemoradiation and surgery (trimodality therapy [TMT]) remain empiric. The authors hypothesized that the frequency, type, and timing of relapses after TMT would be highly associated with surgical pathology stage (SPS), and therefore SPS could be used to individualize the surveillance strategy. Between 2000 and 2010, 518 patients with EAC were identified who underwent TMT at The University of Texas MD Anderson Cancer Center and were frequently surveyed. Frequency, type, and timing of the first relapse (locoregional and/or distant) were tabulated according to SPS. Standard statistical approaches were used. The median follow-up time after esophageal surgery was 55.4 months (range, 1.0-149.2 months). Disease relapse occurred in 215 patients (41.5%). Higher SPS was associated with a higher rate of relapse (0/I vs II/III, P≤.001; 0/I vs II, P=.002; SPS 0/I vs III, P≤.001; and SPS II vs III, P=.005) ...
Journal of Clinical Oncology, 2014
Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimoda... more Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimodality therapy [BMT]) experience frequent relapses. In a large cohort, we assessed the timing, frequency, and types of relapses during an aggressive surveillance program and the value of the salvage strategies. Patients with EC (N = 276) who received BMT were analyzed. Patients who had surgery within 6 months of chemoradiotherapy were excluded to reduce bias. We focused on local relapse (LR) and distant metastases (DM) and the salvage treatment of patients with LR only. Standard statistical methods were applied. The median follow-up time was 54.3 months (95% CI, 48.4 to 62.4). First relapses included LR only in 23.2% (n = 64), DM with or without LR in 43.5% (n = 120), and no relapses in 33.3% (n = 92) of patients. Final relapses included no relapses in 33.3%, LR only in 14.5%, DM only in 15.9%, and DM plus LR in 36.2% of patients. Ninety-one percent of LRs occurred within 2 years and 98% occurred within 3 years of BMT. Twenty-three (36%) of 64 patients with LR only underwent salvage surgery, and their median overall survival was 58.6 months (95% CI, 28.8 to not reached) compared with those patients with LR only who were unable to undergo surgery (9.5 months; 95% CI, 7.8 to 13.3). Unlike in patients undergoing trimodality therapy, for whom surveillance/salvage treatment plays a lesser role,(1) in the BMT population, approximately 8% of all patients (or 36% of patients with LR only) with LRs occurring more than 6 months after chemoradiotherapy can undergo salvage treatment, and their survival is excellent. Our data support vigilant surveillance, at least in the first 24 months after chemotherapy, in these patients.
Lung Cancer, 2003
Results: The study was well balanced between the two treatment arms in terms on age, sex, KPS and... more Results: The study was well balanced between the two treatment arms in terms on age, sex, KPS and distribution of metastasis. The second line chemotherapy used in patients of GV arm was carboplatin. No statistically significant difference was observed in overall survival (GV vs CGV) (median 275 vs 300 days; 1 year survival 26 vs 28%; p: 0.8) as well as in progression free survival (median 150 vs 175 days; p: 0.4). The objective response rates were 40% for GV and 48% for CGV (p: 0.4). Pts in CGV had more haematological and non-haematological toxicity including the only toxic death registered in this study. Major toxicity grade 3-4 registered were (GV vs CGV; %); Anaemia (23 vs 38;~: 0.04) neutropenia (26 vs 48; p: 0.004); plaquetopenia (2 vs 14; p:O.Oi) and neuropathy (4 vs 22; p: 0.007. Thrombocytosis was registered in 58% and 35% of pts treated with GV and CGV respectively which was associated with a thrombotic episode in 14% of cases in both arms. Dose reduction and/or delay of schedule of treatment were made in 60% and 73% of pts in GV and CGV arm respectively.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014
MicroRNAs (miRNAs) are small, highly conserved non-coding RNAs that regulate many biological proc... more MicroRNAs (miRNAs) are small, highly conserved non-coding RNAs that regulate many biological processes. We sought to investigate whether three serum miRNAs related to immunity or inflammation were associated with esophagitis induced by chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). We measured serum miR-155, miR-221 and miR-21, before and during week 1-2 of CRT for 101 NSCLC patients by real-time PCR. Associations between miRNA and severe radiation-induced esophageal toxicity (RIET) were analyzed by logistic regression. We found that patients with stage IIIB-IV disease, higher mean esophagus dose or esophageal V50 had higher rates of severe RIET. Furthermore, high levels of miR-155 and miR-221 at week 1-2 of CRT were also risk factors for severe RIET (miR-155: OR=1.53, 95% CI: 1.04-2.25, P=0.03; miR-221: OR=2.07, 95% CI: 1.17-3.64, P=0.012). In addition, the fold change of miR-221 was also predictive of severe RIET (OR=1.18, 95% CI: 1.02-1.37, P=0.026). However...
Practical radiation oncology
To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the... more To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the United States. A survey of 36 questions was designed to collect information regarding practice patterns of radiation oncologists for the management of patients with NSCLC. All American Society for Radiation Oncology members were invited to respond. Four hundred twenty-four responses from radiation oncologists in the United States were received. The response rate for the survey was approximately 20%. Substantial discrepancies were seen in the use of stereotactic body radiation therapy (SBRT) for patients with peripherally and centrally located early-stage tumors and in the recommended SBRT dose. There was a near consensus opinion regarding the use of concurrent chemotherapy and the radiation dose for patients with inoperable stage II and III NSCLC with a good performance status; however, in patients with a poor performance status or in patients with stage IV disease treatment recommendat...
American Journal of Clinical Oncology-cancer Clinical Trials, 1985
Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirm... more Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirmed inoperable or unresectable carcinoma of the lung of all cell types were treated with curative intent. Forty-five patients lived a minimum of 3 years and 32 patients lived 5 or more years. The 3-year survival rate increased from 7.6% (15/197) between January, 1971 and June, 1975 to 14.1% (30/213) for the interval from July, 1975 to August, 1978 (p less than 0.01). Factors associated with long-term survival were performance status (p less than 0.01), early stage (p less than 0.001), high total dose of radiation (p less than 0.02), large cell carcinoma (p less than 0.01), inoperable for medical reasons (p less than 0.001), and thoracotomy to determine unresectability (p less than 0.04). The difference in survival rates between the two time periods was not related to different patient factors. Survival rates were most improved in the second time period for patients with Stage II or Stage III carcinoma of the lung. Eight patients died from cancer between 36 and 54 months of initial treatment. Five patients died of intercurrent disease without evidence of cancer of the lung after 3 years. An increasing proportion of long-term survivors of inoperable carcinoma of the lung can be expected to result from a better understanding of these diseases, more technically sophisticated external irradiation, and the use of combination chemotherapy for small cell carcinoma.
Journal of Thoracic Oncology, 2008
We investigated the value of lung perfusion imaging in predicting the risk of developing pulmonar... more We investigated the value of lung perfusion imaging in predicting the risk of developing pulmonary complications after chemoradiation (CRT) or radiation therapy (RT) for lung cancer. Fifty patients who underwent lung perfusion imaging before RT for lung cancer were included. Planar and single photon emission computed tomography/computed tomography images of the lungs were obtained. Lung perfusion score (LPS) was developed to visually grade localized perfusion defect per lung on a scale of 0 to 4 and perfusion pattern in the remaining lungs on a scale of 1 to 4. The LPS is the sum of the score for the localized perfusion defect in each lung plus the score for the remaining lungs perfusion. LPSs were correlated with pulmonary function tests and the patients were followed for 8 months after therapy to determine the incidence of grade 2 to 5 symptomatic therapy related pulmonary complications according to the common terminology criteria for adverse events (CTCAE 3.0). Thirty-four patients underwent CRT and 16 underwent RT. The mean total radiation dose delivered was 56.1 +/- 10.4 Gy. Eighteen patients (36%) suffered from pulmonary complications at a mean interval of 3.4 months after therapy. Nine patients had grade 2, 7 had grade 3, 1 had grade 4, and 1 had grade 5 pulmonary complications. The mean LPS was 4.9 in patients who developed pulmonary complications versus 3.5 in patients who did not (p = 0.01). There were no significant difference between pulmonary function tests in the patients with pulmonary complications and the patient without. In addition, there were no significant differences between the mean lung radiation dose, the volume of lung irradiated or the percentage of lung receiving greater than 20 Gy between the two groups. LPS using lung perfusion imaging is useful for predicting possible pulmonary complications after CRT or RT in lung cancer patients.
New England Journal of Medicine, 1999
For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic ... more For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001). Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.
Nature Medicine, 1996
A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was ... more A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was produced to mediate transfer of wild-type p53 into human non-small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector-related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector-p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.
Lung Cancer, 2005
In LD-SCLC, combined modality therapy has emerged as the standard of practice in good performance... more In LD-SCLC, combined modality therapy has emerged as the standard of practice in good performance status (PS) patients (pts). Pignon&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s meta-analysis [N Engl J Med 1992;327:1618-24] showed that combination chemotherapy (CT) and thoracic radiation (XRT) in LD-SCLC yielded an absolute 5.4% increase in 3-year survival versus chemotherapy alone. Concurrent chemoradiation upfront has generated the highest survival rates [Murray. J Clin Oncol 1993;11:336-44; Jeremic. J Clin Oncol 1996;15:893-900; Takada. J Clin Oncol 2002;20:3054-60]. In stage III NSCLC, multiple studies have shown therapeutic superiority for combination chemotherapy and XRT versus RT alone; and recent literature suggests a therapeutic advantage for concurrent chemoradiation versus chemotherapy followed by XRT [Curran. ASCO 2000;19:484a; Furuse. JCO 1999;17:2692-9; Zatloukal. ASCO 2002;A-1159]. Data are less secure regarding the role of chemotherapy in stage I and II NSCLC. A stratified two-step cluster sampling technique was used for data collection. Five hundred and forty-one individuals diagnosed between 1998 and 1999 with lung cancer, either LD-SCLC or stages I-III NSCLC were sampled from 58 institutions featuring radiotherapy facilities, giving a weighted sample size (wss) of 42,335 patients. All pts had Karnofski performance status (KPS) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=60. We determined the percentage who received chemotherapy; the nature of chemotherapy and its timing with respect to XRT. SUDAAN statistical software was used to allow the incorporation of the design elements and weights to reflect the relative contribution of each institution and each patient in the analysis Of 72 (wss=6138) pts with LD-SCLC, 100% received XRT and 95% received chemotherapy (CT); 66% received concurrent (con) CT and XRT, of whom 29% also received CT pre XRT; 22% received CT post XRT as well, and 23% received both: 63% received sequential CT--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;XRT+/-con CT; and 38% received some CT after XRT. Fifty-two percent received cisplatin (DDP), and 38% received carboplatin (CBDCA); 73% received etoposide (VP-16), while 10% received paclitaxel. Of 469 pts (wss=36,197) with NSCLC, 52% received CT, including 30% with stage I disease, 48% with stage II NSCLC, 60% with stage III NSCLC, and 50% with unknown stage. Thirty-nine percent received sequential CT--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;XRT+/-CT, of whom 49% received CT pre XRT only. Seventy-four percent received con CT and XRT; and 27% received posterior CT, of whom 84% also received con CT/XRT. Forty-five received some CT in the pre-op setting and 15% in the post-op setting. Twelve percent received DDP-based therapy, while only 13% and 7% received VP-16 or vincas, respectively; 67% received CBDCA. Seventy-two percent received taxanes, of whom 96% received paclitaxel. Gemcitabine was administered to 3% of NSCLC pts. Combined modality therapy is typically employed in the therapy of LD-SCLC and LA-NSCLC. The majority of those treated for SCLC receive concurrent CT/XRT, while nearly 3/4 of those treated with CT and XRT for LA-NSCLC received concurrent CT/XRT. Current practice in the US generally matches evidence-based literature, although a significant percentage of practitioners substitute CBDCA for DDP in both venues and use paclitaxel in lieu of vincas or etoposide in NSCLC.
Lung Cancer, 2004
Unresectable;
International Journal of Radiation Oncology*Biology*Physics, 2014
Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We ass... more Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received !60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade !3 or grade !2 RP. Median lung volume receiving !20 Gy (V 20 ) was 31%, and post-RT WBC counts ranged from 1.7 to 21.2 Â 10 3 WBCs/mL. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursivepartitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade !3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 Â 10 3 /mL for grade !3 and !2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade !3 (nZ46, ORZ2.6, 95% confidence interval [CI] 1.4-4.9, PZ.003) and grade !2 RP (nZ164, ORZ2.0, 95% CI 1.2-3.4, PZ.01). This association held in a stepwise multivariate regression. Of note, V 20 was found to be significantly associated with grade !2 RP (ORZ2.2, 95% CI 1.2-3.4, PZ.01) and trended toward significance for grade !3 RP (ORZ1.9, 95% CI 1.0-3.5, PZ.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity. Ó
International Journal of Radiation Oncology*Biology*Physics, 2006
To assess the association of clinical and especially dosimetric factors with the incidence of pos... more To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy) was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V(dose) and absolute V(dose)), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS(dose)). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V(dose) or VS(dose)) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving…
International Journal of Radiation Oncology*Biology*Physics, 2007
To investigate the ability of four-dimensional computed tomography (4D CT)-derived ventilation im... more To investigate the ability of four-dimensional computed tomography (4D CT)-derived ventilation images to identify regions of highly functional lung for avoidance in intensitymodulated radiotherapy (IMRT) planning in locally advanced non-small cell lung cancer (NSCLC).