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We investigated predictions from 18F-FDG PET/CT using machine learning (ML) to assess the neoadjuvant CCRT response of patients with stage III non-small cell lung cancer (NSCLC) and compared them with predictions from conventional PET parameters and from physicians. A retrospective study was conducted of 430 patients. They underwent 18F-FDG PET/CT before initial treatment and after neoadjuvant CCRT followed by curative surgery. We analyzed texture features from segmented tumors and reviewed the pathologic response. The ML model employed a random forest and was used to classify the binary outcome of the pathological complete response (pCR). The predictive accuracy of the ML model for the pCR was 93.4%. The accuracy of predicting pCR using the conventional PET parameters was up to 70.9%, and the accuracy of the physicians’ assessment was 80.5%. The accuracy of the prediction from the ML model was significantly higher than those derived from conventional PET parameters and provided by physicians (p < 0.05). The ML model is useful for predicting pCR after neoadjuvant CCRT, which showed a higher predictive accuracy than those achieved from conventional PET parameters and from physicians.

Purpose: To evaluate the efficacy and safety of ablative dose hypofractionated proton beam therapy (PBT) for patients with stage I and recurrent non-small cell lung carcinoma (NSCLC)., Patients and Methods: A total of 55 patients with stage I (n = 42) and recurrent (n = 13) NSCLC underwent hypofractionated PBT and were retrospectively reviewed. A total dose of 50-72 CGE (cobalt gray equivalent) in 5-12 fractions was delivered., Results: The median follow-up duration was 29 months (range 4-95 months). There were 24 deaths (43.6%) during the follow-up period: 11 died of disease progression and 13 from other causes. Kaplan-Meier overall survival rate (OS) at 3 years was 54.9% and the median OS was 48.6 months (range 4-95 months). Local progression was observed in 7 patients and the median time to local progression was 9.3 months (range 5-14 months). Cumulative actuarial local control rate (LCR), lymph node metastasis-free survival, and distant metastasis-free survival rates at 3 years were 85.4, 78.4, and 76.5%, respectively. Larger tumor diameter was significantly associated with poorer LCR (3-year: 94% for ≤3 cm vs. 65% for >3 cm, p = 0.006) on univariate analysis and also an independent prognostic factor for LCR (HR 6.9, 95% CI = 1.3-37.8, p = 0.026) on multivariate analysis. No grade 3 or 4 treatment-related toxicities developed. One grade 5 treatment-related adverse event occurred in a patient with symptomatic idiopathic pulmonary fibrosis., Conclusions: Ablative dose hypofractionated PBT was safe and promising for stage I and recurrent NSCLC.

Purpose: The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS., Materials and Methods: The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV., Results: The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB., Conclusion: The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Purpose: We retrospectively compared the treatment outcomes of localized prostate cancer between radical prostatectomy (RP) and external beam radiotherapy (EBRT)., Materials and Methods: We retrospectively analyzed 738 patients with localized prostate cancer who underwent either RP (n = 549) or EBRT (n = 189) with curative intent at our institution between March 2001 and December 2011. Biochemical failure was defined as a prostate-specific antigen (PSA)  level of ≥ 0.2 ng/ml in the RP group and the nadir of + ≥ 2 ng/ml in the EBRT group., Results: The median (range) follow-up duration was 48.8 months (0.7-133.2 months) and 48.7 months (1.0-134.8 months) and the median age was 66 years (45-89 years) and 71 years (51-84 years; p < 0.001) in the RP and EBRT groups, respectively. Overall, 21, 42, and 36 % of patients in the RP group, and 15, 27, and 58 % of patients in the EBRT group were classified as low, intermediate, and high risk, respectively (p < 0.001). Androgen-deprivation therapy was more common in the EBRT group (59 vs. 27 %, respectively; p < 0.001). The 8-year biochemical failure-free survival rates were 44 and 72 % (p < 0.001) and the disease-specific survival rates were 98 % and 97 % (p = 0.543) in the RP and EBRT groups, respectively., Conclusions: Although the EBRT group included more high-risk patients than did the RP group, the outcomes of EBRT were not inferior to those of RP. Our data suggest that EBRT is a viable alternative to RP for treating localized prostate cancer.

Background and Purpose: To assess the location of recurrent tumors and suggest the optimal target volume in adjuvant or salvage radiotherapy (RT) after a radical prostatectomy (RP)., Material and Methods: From January 2000 to December 2012, 113 patients had been diagnosed with suspected recurrent prostate cancer by MRI scan and received salvage RT in the Samsung Medical Center. This study assessed the location of the suspected tumor recurrences and used the inferior border of the pubic symphysis as a point of reference., Results: There were 118 suspect tumor recurrences. The most common site of recurrence was the anastomotic site (78.8%), followed by the bladder neck (15.3%) and retrovesical area (5.9%). In the cranial direction, 106 (87.3%) lesions were located within 30 mm of the reference point. In the caudal direction, 12 lesions (10.2%) were located below the reference point. In the transverse plane, 112 lesions (94.9%) were located within 10mm of the midline., Conclusions: A MRI scan acquired before salvage RT is useful for the localization of recurrent tumors and the delineation of the target volume. We suggest the optimal target volume in adjuvant or salvage RT after RP, which includes 97% of suspected tumor recurrences., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Hypofractionated radiotherapy potentially offers therapeutic gain for prostate cancer. We investigated the feasibility of hypofractionated proton therapy (PT)., Material and Methods: Eighty-two patients with biopsy-proven T1-3N0M0 prostate adenocarcinoma and no history of androgen deprivation therapy were randomly assigned to five different dose schedules: Arm 1, 60 CGE (cobalt gray equivalent = proton dose in Gy × 1.1)/20 fractions/5 weeks; Arm 2, 54 CGE/15 fractions/5 weeks; Arm 3, 47 CGE/10 fractions/5 weeks; Arm 4, 35 CGE/5 fractions/2.5 weeks; or Arm 5, 35 CGE/5 fractions/5 weeks., Results: The median follow-up duration was 42 months (11-52 months). The acute GI and GU grade ≥ 2 toxicity rates were 0 and 5%, respectively. The late GI and GU grade ≥ 2 toxicity rates were 16% and 7%, respectively. The best arm for acute GU toxicity was Arm 3, while that for late GI toxicity was Arm 2 in which none had grade ≥ 2 toxicity. The four-year American Society for Therapeutic Radiology and Oncology and Nadir + 2ng/ml BCF free survival (BCFFS) rates were 85% and 86%, respectively., Conclusions: Hypofractionated PT for patients with prostate adenocarcinoma as used in this study is feasible with an acceptable toxicity profile. As the BCFFS rates do not seem to be inferior to those produced using conventional fractionation, the application of hypofractionated PT may save patients time and money.

Purpose: To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals., Materials and Methods: Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only., Results: The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS., Conclusion: The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery.

The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, DNA damage checkpoint signaling pathway activation after irradiation has received increasing attention. The association between the expression levels and survival outcome was evaluated to find possible therapeutic targets in brain metastasis. Radiosensitivity of human non-small cell lung cancer cell lines was determined by checking their viability after treatment with varying doses of ionizing radiation (IR). The expression of DNA checkpoint proteins was analyzed by Western blots and immunohistochemistry. On the basis of the clinical data for the patients, the association between the expression of the components and patients' survival was investigated. The expression levels of TopBP1 and phosphorylated Chk1 (P-Chk1) protein were higher in radioresistant lung cancer cell lines compared to radiosensitive cell lines. We previously assessed radiation survival of lung cancer cell lines after treating them with Chk1 inhibitor, AZD7762. AZD7762 significantly sensitized both radioresistant and radiosensitive cells to IR. We also observed a strong inverse relationship between progression-free survival (PFS) and expression level of P-Chk1 and TopBP1. This study, which is the first clinical report that connects DNA damage checkpoints and prognosis of brain metastasis, supports these two proteins to be promising targets for overcoming the radioresistance in brain metastasis.

Purpose: We analyzed outcomes of simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in patients with high-grade gliomas, compared with a literature review., Methods and Materials: Forty consecutive patients (WHO grade III, 14 patients; grade IV, 26 patients) treated with SIB-IMRT were analyzed. A dose of 2.0 Gy was delivered to the planning target volume with a SIB of 0.4 Gy to the gross tumor volume with a total dose of 60 Gy to the gross tumor volume and 50 Gy to the planning target volume in 25 fractions during 5 weeks. Twenty patients received temozolomide chemotherapy., Results: At a median follow-up of 13.4 months (range, 3.7-55.9 months), median survival was 14.8 months. One- and 2-year survival rates were 78% and 65%, respectively, for patients with grade III tumors and 56% and 31%, respectively, for patients with grade IV tumors. Age (≤50 vs. >50), grade (III vs. IV), subtype (astrocytoma vs. oligodendroglioma or mixed), and a Zubrod performance score (0-1 vs. >2) were predictive of survival. Of 25 (63%) patients who had recurrences, 17 patients had local failure, 9 patients had regional failure, and 1 patient had distant metastasis. Toxicities were acceptable., Conclusions: SIB-IMRT with the dose/fractionation used in this study is feasible and safe, with a survival outcome similar to the historical control. The shortening of treatment time by using SIB-IMRT may be of value, although further investigation is warranted to prove its survival advantage., (2010 Elsevier Inc. All rights reserved.)

Purpose: On the basis of the benefits of frontline radiation in early-stage, extranodal, natural killer (NK)/T-cell lymphoma (ENKTL), we conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of etoposide, ifosfamide, cisplatin, and dexamethasone (VIPD)., Patients and Methods: Thirty patients with newly diagnosed, stages IE to IIE, nasal ENKTL received CCRT (ie radiation 40 to 52.8 Gy and cisplatin 30 mg/m(2) weekly). Three cycles of VIPD (etoposide 100 mg/m(2) days 1 through 3, ifosfamide 1,200 mg/m(2) days 1 through 3, cisplatin 33 mg/m(2) days 1 through 3, and dexamethasone 40 mg days 1 through 4) were scheduled after CCRT., Results: All patients completed CCRT, which resulted in 100% response that included 22 complete responses (CRs) and eight partial responses (PRs). The CR rate after CCRT was 73.3% (ie, 22 of 30 responses; 95% CI, 57.46 to 89.13). Twenty-six of 30 patients completed the planned three cycles of VIPD, whereas four patients did not because they withdrew (n = 2) or because they had an infection (n = 2). The overall response rate and the CR rate were 83.3% (ie; 25 of 30 responses; 95% CI, 65.28 to 94.36) and 80.0% (ie, 24 of 30 responses; 95% CI, 65.69 to 94.31), respectively. Only one patient experienced grade 3 toxicity during CCRT (nausea), whereas 12 of 29 patients experienced grade 4 neutropenia. The estimated 3-year, progression-free and overall survival rates were 85.19% (95% CI, 72.48 to 97.90) and 86.28% (95% CI, 73.97 to 98.59), respectively., Conclusion: Patients with newly diagnosed, stages IE to IIE, nasal ENKTL are best treated with frontline CCRT.

Purpose: We evaluated the efficacy of synchronous three-dimensional (3D) conformal boost to the gross tumor volume (GTV) in concurrent chemoradiotherapy for patients with locally advanced non-small-cell lung cancer (NSCLC)., Methods and Materials: Eligibility included unresectable Stage III NSCLC with no pleural effusion, no supraclavicular nodal metastases, and Eastern Cooperative Oncology Group performance score of 0-1. Forty-nine patients with pathologically proven NSCLC were enrolled. Eighteen patients had Stage IIIA and 31 had Stage IIIB. By using 3D conformal radiotherapy (RT) techniques, a dose of 1.8 Gy was delivered to the planning target volume with a synchronous boost of 0.6 Gy to the GTV, with a total dose of 60 Gy to the GTV and 45 Gy to the planning target volume in 25 fractions during 5 weeks. All patients received weekly chemotherapy consisting of paclitaxel and carboplatin during RT., Results: With a median follow-up of 36.8 months (range, 29.0-45.5 months) for surviving patients, median survival was 28.1 months. One-, 2- and 3-year overall survival rates were 77%, 56.4%, and 43.8%, respectively. Corresponding local progression-free survival rates were 71.2%, 53.7%, and 53.7%. Compliance was 90% for RT and 88% for chemotherapy. Acute esophagitis of Grade 2 or higher occurred in 29 patients. Two patients with T4 lesions died of massive bleeding and hemoptysis during treatment (Grade 5). Overall late toxicity was acceptable., Conclusions: Based on the favorable outcome with acceptable toxicity, the acceleration scheme using 3D conformal GTV boost in this trial is warranted to compare with conventional fractionation in a Phase III trial.

Objective: To determine whether cyclooxygenase-2 (COX-2) expression in pretreatment biopsy specimens is a useful predictive marker of tumor response to preoperative chemoradiation (CRT) in rectal cancer., Design: Case series., Setting: Colorectal cancer clinic., Patients: Thirty patients with locally advanced rectal cancer were given preoperative CRT of 5040 cGy for 6 weeks with concurrent administration of 5-fluorouracil and leucovorin., Main Outcome Measures: Immunohistochemical staining for COX-2 and angiogenesis markers (vascular endothelial growth factor, thymidine phosphorylase, and CD34) were performed on biopsy specimens obtained before preoperative CRT. The responses to preoperative CRT were assessed by radiologic downsizing (measured using magnetic resonance imaging volumetry), histopathologic downstaging, and a 3-point tumor regression grade (TRG) evaluation, based on the ratio of residual cancer to fibrosis., Results: Tumor downstaging was seen in 15 patients (50.0%) and nodal downstaging was noted in 14 patients (46.7%). Tumor regression grade 1 (good response) was shown by 7 patients (23.3%); TRG2 (moderate response) in 15 patients (50.0%); and TRG3 (poor response) in 8 patients (26.7%). Patients with COX-2 overexpression were more likely to show a poor TRG (P = .003) and were less likely to achieve histopathologic nodal downstaging (P = .03) than those with normal COX-2 expression. Vascular endothelial growth factor overexpression was found to be associated with COX-2 overexpression (P = .02)., Conclusions: Overexpression of COX-2 in pretreatment biopsies might be predictive of poor tumor regression after preoperative CRT. Administration of COX-2 inhibitors to patients with COX-2 overexpression, in an attempt to improve response rate to preoperative CRT, warrants assessment in clinical trials.

Background: The purpose of the current study was to investigate the role of amifostine and epoetin-alpha in reducing severe toxicities during concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC)., Methods: Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (Days 1-3) with concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-alpha at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply., Results: Amifostine treatment was associated with higher febrile neutropenia (P = .003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P = .03). It also demonstrated a trend toward higher grade 4 leukopenia (P = .05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-alpha (P = .059). Epoetin-alpha treatment was associated with less grade 2 or 3 anemia (P = .031) and lower decreases in hemoglobin level during CCRT (P = .016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-alpha arm; P = .447)., Conclusions: Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-alpha was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated.

Purpose: To quantify proton radiotherapy dose reduction in the prostate target volume because of the three-dimensional movement of the prostate based on an analysis of dose-volume histograms (DVHs)., Methods and Materials: Twelve prostate cancer patients underwent scanning in supine position, and a target contour was delineated for each using a proton treatment planning system. To simulate target movement, the contour was displaced from 3 to 15 mm in 3-mm intervals in the superior-to-inferior (SI), inferior-to-superior (IS), anterior-to-posterior (AP), posterior-to-anterior (PA), and left-to-right (LR) directions., Results: For both intra- and interfractional movements, the average coverage index and conformity index of the target were reduced in all directions. For interfractional movements, the magnitude of dose reduction was greater in the LR direction than in the AP, PA, SI. and IS directions. Although the reduction of target dose was proportional to the magnitude of intrafractional movement in all directions, a proportionality between dose reduction and the magnitude of interfractional target movement was clear only in the LR direction. Like the coverage index and conformity index, the equivalent uniform dose and homogeneity index showed similar reductions for both types of target movements., Conclusions: Small target movements can significantly reduce target proton radiotherapy dose during treatment of prostate cancer patients. Attention should be given to interfractional target movement along the longitudinal direction, as image-guided radiotherapy may be ineffective if margins are not sufficient.

Background: This randomized pilot trial investigated whether primary chemotherapy was feasible in terms of efficacy, survival, toxicity profile, and quality of life compared with whole-brain radiotherapy (WBRT) given first in chemotherapy-naive patients nonsmall cell lung cancer (NSCLC) with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled by supportive care., Methods: After stratification by Eastern Cooperative Oncology Group performance status (ECOG PS) (0-1 vs 2), the number of intracranial metastases (<3 vs 3< or =), and the presence of extrathoracic extracranial metastasis, eligible patients were randomized to the primary chemotherapy arm or the WBRT-first arm. World Health Organization (WHO) response criteria, National Cancer Institute Common Toxicity Criteria (NCI-CTC; version 2.0), and the European Organization for Research and Treatment of Cancer (EORTC) C-30/LC-13 questionnaire were used., Results: A total of 48 patients were enrolled between August 2002 and November 2005. The response rate of chemotherapy and survival outcomes in the primary chemotherapy arm were not statistically different from those in the WBRT-first arm (overall response rate, 28.0% vs 39.1%; progression-free survival, 3.6 months vs 4.4 months; overall survival, 9.1 months vs 9.9 months). There was close correlation noted between intracranial and extracranial tumor responses (k = 0.82). However, in the WBRT-first arm, grade 3 of 4 neutropenia was more frequent (79% vs 40%) during chemotherapy and 4 patients (17.4%) did not receive further chemotherapy because of early death or poor performance after WBRT. Cognitive function appeared to deteriorate during primary chemotherapy, but was also found to deteriorate after WBRT., Conclusions: Primary chemotherapy is more feasible and can be an appropriate option for patients with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled. The role and timing of WBRT should be defined in further studies in this clinical setting., ((Copyright) 2008 American Cancer Society.)

Background: Concurrent chemoradiotherapy is commonly used for locally advanced nasopharyngeal carcinoma (NPC). We retrospectively analyzed the clinical outcomes of simultaneous modulated accelerated radiotherapy (SMART) with concurrent chemotherapy., Methods: Between January 2003 and May 2005, 24 patients with stage IIB to IVB NPC underwent SMART encompassing 3 targets: gross tumor volume (GTV), high-risk subclinical disease (CTV1), and low-risk subclinical disease (CTV2). Daily fractions of 2.4, 2.15, and 1.9 Gy were delivered to GTV, CTV1, and CTV2 to a total dose of 64.8, 58.05, and 51.3 Gy in 27 fractions over 5.5 weeks, respectively. Fifteen patients received concurrent cisplatin (DDP group), and 9 received 5-fluorouracil plus cisplatin (FP group)., Results: With a median follow-up of 26 months (range, 17-45 months), 3-year overall and local-, regional-, and distant-progression-free survivals were 96% and 93%, 87%, and 88%, respectively. Grade 3 acute mucositis and pharyngitis were observed in 16 (67%) and 14 (59%) patients, respectively. Severe acute mucositis (100% vs 47%) and pharyngitis (100% vs 34%) were more frequently observed in the FP group than the DDP group (p < .01)., Conclusions: Despite short follow-up with a small number of patients, our preliminary results demonstrated encouraging local-regional control and survival at the cost of modest increase in treatment related toxicities. The total dose and fractionation scheme of SMART used in our study is feasible with no life-threatening or fatal complications. However, the administration of fluorouracil in addition to cisplatin during SMART was associated with increased acute and late toxicities, and it should be administered with caution.

Purpose: Dose uniformity in cell culture vessels such as Petri dishes and anoxic irradiation chambers is very important in radiobiological work as dose uniformity affects cell survival probabilities. In this study, we investigated X-ray dose inhomogeneity, caused by scattering, in typical culture vessels., Materials and Methods: Three different cubic cell culture vessels, with side lengths of 10 cm, 15 cm and 20 cm, were designed and irradiated by X-rays of 6 MV and 15 MV at a source-to-surface distance (SSD) of 100 cm using a Varian 2,100CD linear accelerator., Results: The relative X-ray dose distribution in a cell culture vessel depended strongly on whether the vessel had a lid. The percentage of the cell culture surface with the dose differing by more than 10% from the mean value of the dose was 43.4% in lidless vessels and 9.7% in lidded vessels., Conclusions: In radiobiological work, X-ray dose inhomogeneity within a cell culture vessel is not negligible and the placement of cells in the vessel should be carefully considered.

The goal of the present study was to develop a new dose-volume histogram (DVH)- based homogeneity index for effectively evaluating the dose homogeneity of intensity-modulated radiotherapy plans. The new index, called the sigma-index ("S-index") is defined as the standard deviation of the normalized differential DVH curve. In a study of 16 patients with brain tumors at our institution, the S-index was found to vary from 0.80 to 3.15. Our results showed that the S-index provides a more reliable and accurate measure of dose homogeneity than that given by conventional methods. A guideline for evaluating the dose homogeneity of treatment plans based on the S-index and its relation to equivalent uniform dose is discussed.

Purpose: Gastrointestinal stromal tumors (GISTs) rarely originate in the rectum. We investigated the clinicopathologic characteristics of rectal GISTs., Methods: We analyzed the medical records of seven patients who underwent surgery for GIST of the rectum between 1998 and 2003., Results: There were two men and five women with a median age of 55 years (range, 41-72 years) at the time of diagnosis. The median follow-up period was 23 months (range, 7-75 months). The chief symptoms were hematochezia, constipation, and anal pain. All patients underwent curative resection; in the form of abdominoperineal resection in five patients, transanal excision in one, and Hartmann's operation with prostatectomy in one. The median tumor size was 6.6 cm (range, 1-12 cm). Four patients received adjuvant radiation therapy. Local recurrence developed in two patients; 54 months and 23 months after surgery, respectively., Conclusion: The common symptoms of rectal GIST were the same as those of other rectal tumors. Curative surgical resection should be done, but further studies are necessary to investigate better adjuvant treatment strategies for patients with rectal GISTs.

Purpose: To compare tumor volume reduction rate, histopathologic downstaging, and tumor regression grade (TRG) among tumor responses in rectal cancer after preoperative chemoradiotherapy (CRT)., Patients and Methods: Between 2002 and 2004, 30 patients with locally advanced rectal cancer underwent preoperative CRT, followed by surgical resection. Magnetic resonance volumetry was performed before and after CRT. Histopathologic tumor staging and tumor regression were reviewed. We compared pre- and post-CRT tumor volume and percent of volume reduction, according to histopathologic downstaging and TRG., Results: The tumor volume reduction rates ranged from 14.6% to 100%. Mean pre- and post-CRT tumor volumes were significantly smaller in patients who showed T downstaging than in those who did not (p = 0.040, 0.014). The mean tumor volume reduction was 66.4% vs. 55.2% (p = 0.361). However, the mean pre- and post-CRT tumor volume and mean tumor volume reduction rate between patients who showed N downstaging and those who did not were not statistically different (p = 0.176, 0.767, and 0.899). With respect to TRG, the mean pre- and post-CRT tumor volumes were not statistically significant (p = 0.108, 0.708, and 0.120)., Conclusion: Tumor volume reduction rate does not correlate with histopathologic downstaging and TRG. It might be hazardous to evaluate tumor response with respect to volume reduction and to select the surgical method on this basis.

Purpose: This study was undertaken to determine the parotid gland tolerance dose levels following intensity modulated radiation therapy (IMRT) for treating patients who suffered with head and neck cancer., Materials and Methods: From February 2003 through June 2004, 34 head and neck patients with 6 months of follow-up were evaluated for xerostomia after being treated by IMRT. Their median age was 59 years (range: 29~78). Xerostomia was assessed using a 4-question xerostomia questionnaire score (XQS) and a test for the salivary flow rates (unstimulated and stimulated: USFR and SSFR, respectively). The patients were also given a validated LENT SOMA scale (LSS) questionnaire. Evaluations were performed before IMRT and at 1, 3 and 6 months after IMRT., Results: All 34 patients showed significant changes in the XQS, LSS and Salivary Flow rates (USFR and SSFR) after IMRT. No significant changes in the XQS or LSS were noted in 12 patients who received a total parotid mean dose of 3,100 cGy, significant increases in the XQS and LSS were observed. The USFR and SSFR from the parotid glands in 7 patients who received 2,750 cGy were significantly lower than the baseline values at all times after IMRT., Conclusion: We suggest that the total parotid mean dose should be limited to

Purpose: To perform an intracavitary radiotherapy (ICR) plan comparison between the conventional point A plan (conventional plan) and computed tomography (CT)-guided clinical target volume-based plan (CTV plan) by analysis of the quantitative dose-volume parameters and irradiated volumes of organs at risk in patients with cervical cancer., Methods and Materials: Thirty plans for 192Ir high-dose-rate ICR after 30-40-Gy external beam radiotherapy were investigated. CT images were acquired at the first ICR session with artifact-free applicators in place. The gross tumor volume, clinical target volume (CTV), point A, and International Commission on Radiation Units and Measurements Report 38 rectal and bladder points were defined on reconstructed CT images. A fractional 100% dose was prescribed to point A in the conventional plan and to the outermost point to cover all CTVs in the CTV plan. The reference volume receiving 100% of the prescribed dose (V(ref)), and the dose-volume parameters of the coverage index, conformal index, and external volume index were calculated from the dose-volume histogram. The bladder, rectal point doses, and percentage of volumes receiving 50%, 80%, and 100% of the prescribed dose were also analyzed., Results: Conventional plans were performed, and patients were categorized on the basis of whether the 100% isodose line of point A prescription dose fully encompassed the CTV (Group 1, n = 20) or not (Group 2, n = 10). The mean gross tumor volume (11.6 cm3) and CTV (24.9 cm3) of Group 1 were smaller than the corresponding values (23.7 and 44.7 cm3, respectively) for Group 2 (p = 0.003). The mean V(ref) for all patients was 129.6 cm(3) for the conventional plan and 97.0 cm3 for the CTV plan (p = 0.003). The mean V(ref) in Group 1 decreased markedly with the CTV plan (p < 0.001). For the conventional and CTV plans in all patients, the mean coverage index, conformal index, and external volume index were 0.98 and 1.0, 0.23 and 0.34, and 3.86 and 2.15, respectively. Statistical analysis showed that the conformal index and external volume index improved significantly with the CTV plan, and this improvement was more marked in Group 1. The mean values of the bladder and rectal point doses and volume fractions receiving 50%, 80%, and 100% of the reference dose did not differ between plans for all patients. The reduction in the mean rectal and bladder point doses and irradiated volumes for the CTV plan was statistically significant in Group 1., Conclusion: Computed tomography-guided CTV planning of ICR is superior to conventional point A planning in terms of conformity of target coverage and avoidance of overdosed normal tissue volume. To ascertain the potential benefit of treatment outcome, ICR with image-guided three-dimensional plans will be pursued and correlated with the dose-volume parameters.

Purpose: For locoregionally advanced inoperable non-small-cell lung cancer (NSCLC), concurrent chemoradiotherapy has become a standard therapy. We conducted a Phase II trial to examine the efficacy and toxicity of adding gemcitabine and vinorelbine induction chemotherapy to concurrent chemoradiotherapy with oral etoposide and cisplatin., Methods and Materials: Eligibility included inoperable clinical Stage III NSCLC without pleural effusion, ECOG performance status 0-1, and weight loss < or =5%. Induction chemotherapy consisted of three cycles of gemcitabine 1,000 mg/m2 and vinorelbine 30 mg/m2, each given i.v. on Days 1 and 8, every 3 weeks. During once-daily thoracic radiotherapy (1.8 Gy/day, total 63 Gy), two cycles of oral etoposide (100 mg on Days 1-5 and 8-12) plus cisplatin (50 mg/m2 on Days 1 and 8) were given concurrently 4 weeks apart., Results: Between April 2002 and November 2003, 42 patients were enrolled and 40 were included in response and toxicity evaluation. The median age was 59 years and 13 patients had IIIA and 27 had IIIB; 24 had squamous ca, 12 had adenocarcinoma, and 4 had others. Objective tumor responses were obtained in 29 patients (72.5%), including 18 (45.0%) after induction chemotherapy. After a median follow-up of 23.8 months, the median survival time and progression-free survival was 23.2 months and 10.9 months, respectively, with 2-year survival rate of 43.9%. For the patients with supraclavicular nodal involvement, the median survival time was 11.8 months with 2-year survival rate of 16.7%, whereas the corresponding figures were 27.8 months and 52.0%, respectively, for those without supraclavicular nodal involvement. Toxicity of induction chemotherapy was mild and well tolerated. However, concurrent chemoradiotherapy was associated with G3/4 hematologic toxicity in 75.7%, G3 esophagitis in 24.2%, and two treatment-related deaths. There were nonlife-threatening late toxicities in additional 6 patients., Conclusions: Induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with etoposide and cisplatin showed very promising survival in patients with Stage III NSCLC, especially in those without supraclavicular nodal involvement, which warrants further evaluation.

Purpose: To retrospectively evaluate which dose-volumetric parameters are associated with the risk of > or = Grade 3 acute esophageal toxicity (AET) in lung cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT)., Methods and Materials: One hundred twenty-four lung cancer patients treated curatively with 3D-CRT were retrospectively analyzed. All patients received conventionally fractionated radiotherapy (RT) with median dose of 60 Gy (range, 54-66 Gy) delivered in 30 fractions (range, 27-33 fractions). Thirty-one patients underwent curative surgery before RT. Ninety-two patients received chemotherapy (induction, 18; concurrent +/- induction, 74). Acute esophageal toxicity was scored by Radiation Therapy Oncology Group criteria. The parameters analyzed included sex; age; Karnofsky performance score; weight loss; surgery; concurrent chemotherapy; the percentages of organ volume receiving > or =20 Gy (V20), > or =30 Gy (V30), > or =40 Gy (V40), > or =50 Gy (V50), > or =55 Gy (V55), > or = 58 Gy (V58), > or =60 Gy (V60), and > or =63 Gy (V63); the percent and absolute length of the esophagus irradiated; the maximum and mean dose to the esophagus; and normal tissue complication probability., Results: Of the 124 patients, 15 patients (12.1%) had Grade 3 AET, and 1 (0.8%) patient had Grade 4 AET. There was no fatal Grade 5 AET. In univariate and multivariate logistic regression analyses, concurrent chemotherapy and V60 were significantly associated with the development of severe (> or = Grade 3) AET (p < 0.05). Severe AET was observed in 15 of 74 patients (20.3%) who received concurrent chemotherapy, and in 1 of 50 patients (2.0%) who did not (p = 0.002). Severe AET was observed in 5 of 87 patients (5.7%) with V60 < or = 30% and in 11 of 37 patients (29.7%) with V60 > 30% (p < 0.001). Among 50 patients who did not receive concurrent chemotherapy, severe AET was observed in 0 of 43 patients (0%) with V60 < or = 30% and in 1 of 7 patients (14.2%) with V60 > 30% (p = 0.140). Among 74 patients who received concurrent chemotherapy, severe AET was observed in 5 of 44 patients (11.4%) with V60 < or = 30% and in 10 of 30 patients (33.3%) with V60 > 30% (p = 0.037)., Conclusions: Concurrent chemotherapy and V60 were associated with the development of severe AET > or = Grade 3. For patients being treated with concurrent chemotherapy, V60 is considered to be a useful parameter predicting the risk of severe AET after conventionally fractionated 3D-CRT for lung cancer.

Purpose: To retrospectively evaluate dose-volumetric parameters for association with risk of severe (grade >/=3) radiation pneumonitis (RP) in patients after three-dimensional (3D) conformal radiation therapy for lung cancer., Materials and Methods: The study was approved by the institutional review board, which did not require informed consent. Data from 76 patients (66 men, 10 women; median age, 60 years; range, 35-79 years) with histologically proved lung cancer treated curatively with 3D conformal radiation therapy between August 2001 and October 2002 were retrospectively analyzed. Twenty patients underwent surgery before radiation therapy; 57 patients received chemotherapy. Median total radiation dose of 60 Gy (range, 54-66 Gy) was delivered in 30 (range, 27-33) fractions over 6 weeks. RP was scored by using Radiation Therapy Oncology Group criteria. Clinical parameters were analyzed. Dose-volumetric parameters analyzed were percentage of lung volume that received a dose of 20 Gy or more (V20), 30 Gy or more (V30), 40 Gy or more (V40), or 50 Gy or more (V50); mean lung dose (MLD); normal tissue complication probability (NTCP); and total dose. Fisher exact test was performed to compare clinical parameters between patients who developed severe RP and those who did not. Univariate and multivariate logistic regression analyses were performed to evaluate data for association between dose-volumetric parameters and severe RP. Pearson chi(2) test was used to assess data for correlations among dose-volumetric parameters. P < or = .05 was considered to indicate statistically significant difference., Results: Of 76 patients, 30 (39%) did not develop RP; 23 (30%) developed RP of grade 1; 11 (14%), grade 2; 11 (14%), grade 3; and 1 (1%), grade 4. None had grade 5 RP. Age (< 60 vs > or =60), sex, Karnofsky performance status (< 70 vs > or =70), forced expiratory volume in 1 second, presence of weight loss, preexisting lung disease, history of thoracic surgery, and history of chemotherapy did not significantly differ between patients who developed severe RP and those who did not. In univariate analyses, MLD, V20, V30, V40, V50, and NTCP were associated with severe RP (P < .05). In multivariate analysis, MLD was the only variable associated with severe RP., Conclusion: MLD is a useful indicator of risk for development of severe RP after 3D conformal radiation therapy in patients with lung cancer., ((c) RSNA, 2005.)

Purpose: To determine the differential expression of cyclooxygenase-2 (COX-2) in patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the uterine cervix and the prognostic significance of COX-2 expression in these histologic types., Methods and Materials: A total of 105 International Federation of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were screened for COX-2 expression immunohistochemically. COX-2 expression was determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21). To determine the clinical significance of COX-2 expression by histologic type, the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n = 64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2 positive (n = 12). The clinical response to treatment, patterns of treatment failure, and survival data by COX-2 expression were compared for these two major histologic types. Univariate and multivariate analyses were performed to identify the prognostic factors influencing survival., Results: Immunohistochemical examination showed that COX-2 expression was more frequently observed in ADC than in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important predictor of treatment response, irrespective of the histologic type. All COX-2-negative patients achieved complete remission after initial treatment; 17% of SCC patients and 33% of ADC patients with COX-2 expression did not have complete remission after the initial treatment. The incidence of local failure for those with COX-2 expression was significantly greater than for COX-2-negative patients, regardless of histologic type. With a minimal follow-up of 60 months, the overall 5-year actuarial survival rate for SCC and ADC patients was 79% and 62%, respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic type, COX-2-positive patients had an unfavorable prognosis. The overall 5-year actuarial survival rate was 57% for COX-2-positive patients and 83% for COX-2-negative patients (p = 0.001). When patients were stratified into the four groups according to histologic type and COX-2 expression status, ADC/COX-2-positive patients had the worst prognosis, with an overall 5-year actuarial survival rate of 49% compared with 78% for ADC/COX-2-negative patients, 62% for SCC/COX-2-positive, and 84% for SCC/COX-2-negative patients (p = 0.007, log-rank test). Irrespective of histologic type, COX-2 expression was an independent prognostic factor by univariate and multivariate analyses., Conclusion: In uterine cervical cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC patients. COX-2 expression was also identified as a major determiner of a poor response to treatment and of an unfavorable prognosis, irrespective of the histologic type, reflecting the importance of the COX-2 protein in the acquisition of biologic aggressiveness and more malignant phenotype or increased resistance to the standard chemotherapy and radiotherapy in both histologic types. Given these observations, we believe that that ADC/COX-2-positive patients might be appropriate candidates for future trials of selective COX-2 inhibitor adjunctive therapy.

Purpose: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients., Experimental Design: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared., Results: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03)., Conclusions: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.

Purpose: We retrospectively evaluated the outcome of patients treated with radiotherapy, with or without surgery, for aggressive fibromatosis. The patterns of local failure were analyzed to determine the optimum radiation dose and volume for irradiation., Patients and Methods: Twenty-four patients with histologically confirmed aggressive fibromatosis were treated with radiation therapy at the Yonsei Cancer Center between 1990 and 1998. The radiation dose per patient ranged from 39.6 to 59.4 Gy (mean: 49.4 Gy). The entire operative bed, with a generous margin, was included in the radiotherapy volume. Patients were considered as locally controlled if there was no evidence of the disease during their follow-up period, and if the tumors were stable for more than 2 years. The minimum duration of the follow-up period was 26 months, with a median of 69 months., Results: The actuarial 10-year recurrence-free and overall survival were 88.5 and 100%, respectively. Patients who had a recurrence were salvaged by combined surgery and re-irradiation. Recurrences developed only in patients who had a recurrent disease after surgery and were treated with an inadequate radiation volume. In 9 patients with a gross measurable disease, there were no in-field failures; these had been treated with a median of 50.4 Gy (range: 40-60 Gy) of radiation. Eight patients with a microscopic residual disease were also locally controlled with 41.4-59.4 Gy (median: 45 Gy) of radiation. No patient has developed either secondary malignancy or any serious radiation complications., Conclusion: Radiotherapy for aggressive fibromatosis can be an effective treatment option for maintaining a disease-free status. As fibromatosis, with either a microscopic, or a gross residual disease, can be controlled with a moderate dose of radiation, adjuvant postoperative radiotherapy following surgical excision is recommended with the least sufficient margin to preserve good function and cosmesis. The geographic relationship may require a more precise definition; in addition, regardless of the existence of neighborhood normal tissue barriers, a wide coverage of the radiation volume may be needed., (Copyright 2003 S. Karger AG, Basel)

Background: The objective of this study was to determine whether cyclooxygenase-2 (COX-2) overexpression was an indicator of prognosis in patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine cervical carcinoma who underwent radiation and concurrent chemotherapy., Methods: Seventy-five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the uterine cervix who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996 were divided into two groups according to their COX-2 level in an immunohistochemical study: the COX-2 negative group (n = 54 patients) and the COX-2 positive group (n = 21 patients). The clinicopathologic features, patterns of treatment failure, and survival data for patients in the COX-2 positive group were compared with data from the patients in the COX-2 negative group. Univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival., Results: In the immunohistochemical study, COX-2 overexpression was observed in approximately 30% of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed regression to the initial treatment, the treatment failure rate of patients in the COX-2 positive group was much higher compared with the treatment failure rate of patients in the COX-2 negative group. The higher incidence of central failure and lymph node failure for patients in the COX-2 positive group was statistically significant (48% for the COX-2 positive group vs. 13% for the COX-2 negative group). However, there was no difference in the incidence of hematogenous metastases between the two groups (5% for the COX-2 positive group vs. 7% for the COX-2 negative group). In addition, increased COX-2 expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 9 months in the COX-2 positive group vs. 26 months in the COX-2 negative group). Compared with patients in the COX-2 negative group, patients in the COX-2 positive group had lower overall actuarial and disease free survival rates (overall 5-year actuarial survival rates: 56% for the COX-2 positive group vs. 94% for the COX-2 negative group; P = 0.003). Univariate and multivariate analyses showed that COX-2 overexpression was an independent prognostic factor that surpassed other well-known clinicopathologic parameters., Conclusions: COX-2 overexpression can be used as a potent molecular risk factor in patients with FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy., (Copyright 2002 American Cancer Society.)