Clinical impact of boost irradiation to pelvic lymph node in uterine cervical cancer treated with definitive chemoradiotherapy.

The aim of this study was to analyze tumor control and clinical outcomes of patients with uterine cervical cancer treated by chemoradiotherapy according to pelvic lymph node (PLN) positivity and boost irradiation to PLN and to determine toxicities associated with boost irradiation.We retrospectively reviewed patients with uterine cervical cancer treated with chemoradiotherapy between March 2000 and April 2015. Clinical characteristics, failure pattern, and survival outcomes of patients with or without PLN metastasis and those with or without boost irradiation were analyzed.A total of 80 cases were PLN-negative and 46 were PLN-positive. A total of 11 patients underwent PLN boost irradiation. The 2-year and 5-year overall survival (OS) rates showed significant difference between the PLN-positive and PLN-negative groups (P = .010). The 2-year and 5-year progression-free survival (PFS) rates showed significant difference between the 2 groups (P = .032). The 2-year and 5-year OS rates of the no-boost irradiation group were 82.9% and 58.3%, respectively, whereas all patients in the boost irradiation group were alive at the time of analysis (P = .065). There was no recurrence in the boost irradiation group. The difference in PFS was significant between the boost and the no-boost irradiation groups (P = .023). The 2-year and 5-year pelvic-recurrence free survival (PRFS) did not show significant difference but the tendency of increased risk of pelvic recurrence in no-boost group (boost vs no-boost; 81.9% and 70.2% vs 100% and 100% in 2-year and 5-year PRFS, respectively, P = .156). Boost irradiation to PLN could improve locoregional control especially in large pelvic LN (≥1.5 cm). Our results showed that only 1 acute and late toxicity of higher than grade 3 occurred.PLN metastasis was significant prognostic factor in cervix cancer treated by chemoradiotherapy. In the boost irradiation group, there was no recurrence or death with significantly better PFS. Boost irradiation to PLN is expected to improve locoregional control, but further follow-up and assessment are needed.

Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer.

PURPOSE: To assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife. METHODS: We extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan-Meier analysis. RESULTS: The rate of PSA decrease was maximal in the first month (median -3.34 ng/mL/mo), which then fell gradually with median values of -1.51, -0.32, -0.28, -0.20, and -0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan-Meier analysis calculates an actuarial 5-year BCR-free survival after SBRT using CyberKnife as 80.8%. CONCLUSIONS: PSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer.

Interpretation and Prognostic Value of Positron Emission Tomography-Computed Tomography After Induction Chemotherapy With or Without Radiation in IIIA-N2 Non-small Cell Lung Cancer Patients Who Receive Curative Surgery.

We evaluate the correlation of clinical staging on positron emission tomography-computed tomography (PET-CT) and pathologic staging and the prognostic value of PET-CT after induction chemotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). We analyzed 42 cases of clinical stage IIIA-N2 NSCLC who receive 2 to 4 cycles of preoperative chemotherapy with or without radiation followed by curative resection. The maximum standard uptake value (SUVmax) of the suspected lesion on PET-CT was recorded. PET-CT findings after induction chemotherapy were compared with those of initial PET-CT and pathology after surgery. The accuracy of PET-CT in restaging of the primary tumor after induction chemotherapy was 50.0%. Eighteen (42.8%) of 42 patients were underestimated ycT stage, and 3 (7.1%) of 42 patients was overestimated ycT stage by PET-CT scan. The accuracy of PET-CT in restaging of the nodal disease was 71.4%. Six (14.3%) of 42 patients were underestimated ycN stage, and 6 (14.3%) of 42 patients were overestimated ycN stage as compared with pathologic staging. The 2-year overall survival (OS) and relapse-free survival (RFS) rate were 68.5% and 40.9%, respectively. Complete responders (ycT0N0M0) on PET-CT after induction chemotherapy had a significantly longer RFS time than did incomplete responders (28.3 vs 9.1 months, P = 0.021). Complete response on PET-CT after induction chemotherapy with or without radiation was a good prognosticator for RFS in stage IIIA-N2 NSCLC patients who received surgery. However, response evaluation on PET-CT after induction chemotherapy should be interpreted with caution due to its unacceptable accuracy.

Stereotactic body radiation therapy for prostate cancer patients with old age or medical comorbidity: a 5-year follow-up of an investigational study.

We evaluated 5-year follow-up of stereotactic body radiation therapy (SBRT) with Cyberknife for prostate cancer patients. Forty-five men with prostate adenocarcinoma who received SBRT using Cyberknife from May 2006 to November 2012 were enrolled in this study. They were prostate cancer patients with old age and medical comorbidities who received a total of 36 Gy to the prostate in 5 fractions with either everyday or every other day schedule. Prostate-specific antigen (PSA) levels at initial diagnosis and after radiation were traced. Primary endpoints were biochemical relapse-free survival (bRFS), progression-free survival (PFS), and overall survival (OS). The definition of biochemical relapse was a PSA level of nadir+2 ng/mL. Progression was defined as biochemically or clinically detected disease and the start of salvage therapy. After median follow-up of 63 months, the 5-year bRFS for all patients was estimated at 89.7%. The 5-year PFS was estimated at 71%. Four cases of biochemical relapse were observed, including two patients who experienced locoregional failure and one patient who had distant metastasis with biochemical relapse. The 5-year OS was estimated at 94.3%. There were five deaths, all of which were unrelated to prostate cancer. There was no grade 3 or higher acute complication. Grade 3 or higher late urinary toxicity was reported in 2 (4.4%) of 45 patients. The 5-year survival and toxicity outcome of SBRT using Cyberknife on prostate cancer patients with old age or comorbidities were favorable and safe in an investigational study.

Outcome of postoperative radiotherapy following radical prostatectomy: a single institutional experience.

PURPOSE: This single institutional study is aimed to observe the outcome of patients who received postoperative radiotherapy after radical prostatectomy. MATERIALS AND METHODS: A total of 59 men with histologically identified prostate adenocarcinoma who had received postoperative radiation after radical prostatectomy from August 2005 to July 2011 in Seoul St. Mary's Hospital of the Catholic University of Korea, was included. They received 45-50 Gy to the pelvis and boost on the prostate bed was given up to total dose of 63-72 Gy (median, 64.8 Gy) in conventional fractionation. The proportion of patients given hormonal therapy and the pattern in which it was given were analyzed. Primary endpoint was biochemical relapse-free survival (bRFS) after radiotherapy completion. Secondary endpoint was overall survival (OS). Biochemical relapse was defined as a prostate-specific antigen level above 0.2 ng/mL. RESULTS: After median follow-up of 53 months (range, 0 to 104 months), the 5-year bRFS of all patients was estimated 80.4%. The 5-year OS was estimated 96.6%. Patients who were given androgen deprivation therapy had a 5-year bRFS of 95.1% while the ones who were not given any had that of 40.0% (p < 0.01). However, the statistical significance in survival difference did not persist in multivariate analysis. The 3-year actuarial grade 3 chronic toxicity was 1.7% and no grade 3 acute toxicity was observed. CONCLUSION: The biochemical and toxicity outcome of post-radical prostatectomy radiotherapy in our institution is favorable and comparable to those of other studies.

High-dose-rate brachytherapy for the treatment of vaginal intraepithelial neoplasia.

PURPOSE: Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy. MATERIALS AND METHODS: We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa. RESULTS: Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097). CONCLUSION: HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity.

Stereotactic body radiotherapy for prostate cancer: a preliminary report.

AIMS: We report the results of a retrospective study of stereotactic body radiotherapy (SBRT) using a Cyberknife for prostate cancer. METHODS: In all 29 patients were treated with hypofractionated SBRT using a Cyberknife at median 36 Gy in five fractions. All the patients were treated with a radical aim. Prostate-specific antigen (PSA) was evaluated at baseline and after radiotherapy. Acute (≤3 months) and late (>3 months) urinary and rectal toxicities were recorded according to the CTCAE version 4.0. RESULTS: The median duration of follow up was 41 months. PSA values decreased in a time-dependent way. The median PSA nadir was 0.329 ng/mL, achieved after a median of 23 months' follow up. Two patients had a PSA failure according to the definition of nadir + 2 ng/mL. Eight patients (28%) had a benign PSA bounce at median 9 months after radiotherapy. CTCAE Grade 2 and 3 late urinary toxicities were reported in 3 and 3%, respectively. One patient had exacerbated urinary symptoms and received an operation. There were no severe late rectal toxicities. CONCLUSIONS: The preliminary findings of our study suggest SBRT is feasible for prostate cancer treatment. Further studies with more patients and longer follow-up duration are required.

Comparison between preoperative and postoperative concurrent chemoradiotherapy for rectal cancer: an institutional analysis.

PURPOSE: To evaluate the treatment outcomes of preoperative versus postoperative concurrent chemoradiotherapy (CRT) on locally advanced rectal cancer. MATERIALS AND METHODS: Medical data of 114 patients with locally advanced rectal cancer treated with CRT preoperatively (54 patients) or postoperatively (60 patients) from June 2003 to April 2011 was analyzed retrospectively. 5-Fluorouracil (5-FU) or a precursor of 5-FU-based concurrent CRT (median, 50.4 Gy) and total mesorectal excision were conducted for all patients. The median follow-up duration was 43 months (range, 16 to 118 months). The primary end point was disease-free survival (DFS). The secondary end points were overall survival (OS), locoregional control, toxicity, and sphincter preservation rate. RESULTS: The 5-year DFS rate was 72.1% and 48.6% for the preoperative and postoperative CRT group, respectively (p = 0.05, the univariate analysis; p = 0.10, the multivariate analysis). The 5-year OS rate was not significantly different between the groups (76.2% vs. 69.0%, p = 0.23). The 5-year locoregional control rate was 85.2% and 84.7% for the preoperative and postoperative CRT groups (p = 0.98). The sphincter preservation rate of low-lying tumor showed significant difference between both groups (58.1% vs. 25.0%, p = 0.02). Pathologic tumor and nodal down-classification occurred after the preoperative CRT (53.7% and 77.8%, both p < 0.001). Acute and chronic toxicities were not significantly different between both groups (p = 0.10 and p = 0.62, respectively). CONCLUSION: The results confirm that preoperative CRT can be advantageous for improving down-classification rate and the sphincter preservation rate of low-lying tumor in rectal cancer.

High-dose radiotherapy using helical tomotherapy for vertebral metastasis: early clinical outcomes and cord dose specification.

OBJECTIVE: For several decades, radiotherapy has been widely used to treat metastatic vertebral tumors. This study was designed to assess the feasibility and early clinical outcomes of high-dose radiotherapy to treat such tumors, using helical tomotherapy. METHODS: Between June 2009 and December 2011, 51 sites in 36 patients were treated with high-dose radiotherapy using helical tomotherapy for vertebral metastasis. Treatment outcomes and dosimetric analyses of spinal cord were retrospectively evaluated. RESULTS: Median follow-up was 11.5 months (range, 6-34.6) for surviving patients. The median total dose and the number of fractions in the primary helical tomotherapy arm were 2700 cGy and 3 fractions, respectively. Actuarial 6-month local control rates were 85.7%, and symptomatic vertebral compression fractures developed in five patients after a median of 4.2 (range, 2.9-5.7) months. Among 13 patients with 19 metastatic sites who showed pre-treatment impairment in neurologic function, five patients (with seven sites) in whom symptoms were mild showed improvement in neuronal function. The median pre-treatment pain visual analog scale score of 7 decreased to a median of 3 after helical tomotherapy (P < 0.001) at a median of 1 month (range, 0.5-3.2) of follow-up. No significant morbidity developed during follow-up except for one grade 3 esophagitis. CONCLUSIONS: The use of helical tomotherapy to treat metastatic vertebral tumors appears to be both safe and reliable in terms of local tumor control and early pain relief. Local progression and the risk of compression fracture in patients with pre-existing spinal instability remain the principal factors of limiting improved clinical and functional outcomes. Optimal dose-fractionation schemes and appropriate patient selection are required to achieve better outcomes with high-dose radiotherapy using helical tomotherapy.

Treatment outcome in patients with vulvar cancer: comparison of concurrent radiotherapy to postoperative radiotherapy.

PURPOSE: To evaluate outcome and morbidity in patients with vulvar cancer treated with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy. MATERIALS AND METHODS: The records of 24 patients treated with radiotherapy for vulvar cancer between July 1993 and September 2009 were retrospectively reviewed. All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven patients were treated with primary concurrent chemoradiotherapy, one patient was treated with primary radiotherapy alone, four patients received palliative radiotherapy, and twelve patients were treated with postoperative radiotherapy. RESULTS: Twenty patients were eligible for response evaluation. Response rate was 55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute skin complications of grade III or more during radiotherapy. Late complications were found in 8 patients. 50% (6/12) of patients treated with lymph node dissection experienced severe late complications. One patient died of sepsis from lymphedema. However, only 16.6% (2/12) of patients treated with primary radiotherapy developed late complications. CONCLUSION: Outcome of patients with vulvar cancer treated with radiotherapy showed relatively good local control and low recurrence. Severe late toxicities remained higher in patients treated with both node dissection and radiotherapy.

Outcomes and prognostic factors of cervical cancer after concurrent chemoradiation.

AIM: Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced cervical cancer. This study was undertaken to evaluate the outcomes and the prognostic factors for cervical cancer after CCRT. MATERIAL AND METHODS: The medical records of 174 patients with International Federation of Gynecology and Obstetrics stage IB1-IVA who were treated at three affiliated hospitals of the Catholic University of Korea between January 1999 and December 2008 were reviewed and analyzed. Patients received pelvic radiotherapy with one of three regimens of cisplatin-based chemotherapy concurrently and high-dose rate brachytherapy. The radiation field was extended to include para-aortic lymph nodes, if necessary. RESULTS: The median follow-up period was 29.5 months (range, 5-96 months). Using multivariate analysis, stage (P = 0.014), tumor size (P = 0.043), and clinical response (P = 0.001) had a significant effect on overall survival. Similarly, progression-free survival (PFS) was influenced by stage (P = 0.004), tumor size (P = 0.02), clinical response (P = 0.011), and normalized squamous cell carcinoma antigen level after CCRT (P = 0.007). The 5-year survival rates were 91.7% (standard error, 5.8%) for stages IB1-IIA, 71.5% (standard error, 7.8%) for stage IIB, 44.9% (standard error, 7.8%) for stage III, and 20.9% (standard error, 12.0%) for stage IVA. A total of 151 out of 174 patients (86.8%) completed the planned treatment. Toxicities were manageable with supportive therapy. CONCLUSIONS: Cisplatin-based CCRT is well-tolerated. Good clinical response revealed a favorable correlation to survival. A maximal effort to achieve this goal might prolong survival in patients with cervical cancer.

Long-term follow-up of preoperative pelvic radiation therapy and concomitant boost irradiation in locally advanced rectal cancer patients: a multi-institutional phase II study (KROG 04-01).

PURPOSE: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. METHODS AND MATERIALS: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. RESULTS: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P=.045) and N (P=.032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P=.025) and overall survival (P=.031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. CONCLUSION: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and survival.

The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer.

Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p < 0.0001). The area under the receiver operating curve of serum CEA for the prediction of brain metastasis was 0.724 (p = 0.0001). The present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

The role of postoperative pelvic radiation in stage IV rectal cancer after resection of primary tumor.

PURPOSE: To evaluate the effect of pelvic radiotherapy (RT) in patients with stage IV rectal cancer treated with resection of primary tumor with or without metastasectomy. MATERIALS AND METHODS: Medical records of 112 patients with stage IV rectal cancer treated with resection of primary tumor between 1990 and 2011 were retrospectively reviewed. Fifty-nine patients received synchronous or staged metastasectomy whereas fifty-three patients did not. Twenty-six patients received pelvic radiotherapy. RESULTS: Median overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS) of all patients was 27, 70, and 11 months, respectively. Pathologic T (pT), N (pN) classification and complete metastasectomy were statistically significant factors in OS (p = 0.040, 0.020, and 0.002, respectively). RT did not improve OS or LRFS. There were no significant factors in LRFS. pT and pN classification were also significant prognostic factors in PFS (p = 0.010 and p = 0.033, respectively). In the subgroup analysis, RT improved LRFS in patients with pT4 disease (p = 0.026). The locoregional failure rate of the RT group and the non-RT group were 23.1% and 33.7%, showing no difference in the failure pattern of both groups (p = 0.260). CONCLUSION: Postoperative pelvic RT did not improve LRFS of all metastatic rectal cancer patients; however, it can be recommended to patients with pT4 disease. A complete resection of metastatic masses should be performed if possible.

Lymphovascular invasion is a significant prognosticator in rectal cancer patients who receive preoperative chemoradiotherapy followed by total mesorectal excision.

PURPOSE: This study was designed to identify the significance of lymphovascular invasion as a prognosticator for tumor recurrence and survival in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME). METHODS: Between January 2003 and October 2010, the study included 328 patients with primary rectal cancer who had received preoperative CRT followed by TME. We analyzed the clinicopathologic factors that may be associated with survival, such as age, gender, carcinoembryonic antigen (CEA) value, pathologic T and N stage, tumor response, histologic grade, lymphovascular invasion (LVI), and perineural invasion. RESULTS: Higher pathologic T and N stage, poor tumor response, high-grade histology, and positive LVI were adverse prognostic factors for both disease-free survival (DFS) and overall survival (OS) on the multivariate analysis. Perineural invasion was a significant adverse prognostic factor affecting DFS (P=0.046) but not OS (P=0.08). Increased T and N stage and distant recurrence, but not local recurrence, were significant factors associated with LVI. The LVI-negative group had a higher DFS (71.4 vs. 56.2%, P=0.012) and OS rate (86.7 vs. 63.4%, P=0.020) at 5 years than the LVI-positive group did. CONCLUSIONS: Positive LVI had a negative impact on survival in patients with rectal cancer who received preoperative CRT and TME and is significantly associated with an increased chance of distant recurrence. Based on this finding, more tailored adjuvant chemotherapy is warranted for advanced rectal cancer patients with LVI to reduce the distant dissemination of tumor.

Clinical Responses and Prognostic Indicators of Concurrent Chemoradiation for Non-small Cell Lung Cancer.

PURPOSE: To evaluate treatment outcomes and prognostic factors in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiation. MATERIALS AND METHODS: From January 2005 to June 2009, 51 patients were treated with concurrent chemoradiation for 3 different aims: locally advanced stage III, locally recurrent disease, and postoperative gross residual NSCLC. Median age was 63 years. Distribution of stages by the 6th edition of American Joint Committee on Cancer (AJCC) was as follows: IIIA (37.3%), IIIB (56.9%). Chemotherapy was administered every week concurrently with radiation using one of the following regimens: paclitaxel (60 mg/m(2)), docetaxel+cisplatin (20 mg/m(2)+20 mg/m(2)), cisplatin (30 mg/m(2)). Total radiation dose was 16-66.4 Gy (median, 59.4 Gy). RESULTS: Median follow-up duration was 40.8 months. The overall response rate was 84.3% with 23 complete responses. The median survival duration for the overall patient group was 17.6 months. The 3-year survival rate was 17.8%. A total of 21 patients had recurrent disease at the following sites: loco-regional sites (23.6%), distant organs (27.5%). In the multivariate analysis of the overall patient group, a clinical tumor response (p=0.002) was the only significant prognostic factor for overall survival (OS). In the multivariate analysis of the definitive chemoradiation arm, the use of consolidation chemotherapy (p=0.022), biologically equivalent dose (BED)(10) (p=0.007), and a clinical tumor response (p=0.030) were the significant prognostic factors for OS.The median survival duration of the locally recurrent group and the postoperative gross residual group were 26.4 and 23.9 months, respectively. CONCLUSION: Our study demonstrated that clinical tumor response was significantly associated with OS in the overall patient group. Further investigations regarding the optimal radiation dose in the definitive chemoradiation and the optimal treatment scheme in locally recurrent NSCLC would be required.

Radiation-induced brain injury: retrospective analysis of twelve pathologically proven cases.

PURPOSE: This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). MATERIALS AND METHODS: The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were finally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. RESULTS: Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p = 0.061) and biologically equivalent dose (BED)(3) (p = 0.084) were the only marginally influencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed <6 months after radiotherapy was associated with inferior overall survival rates compared to cases of RIBI that occurred ≥6 months (p = 0.085). CONCLUSION: Our study demonstrated that RIBI could occur in early periods after conventional fractionated brain radiotherapy within normal tolerable dose ranges. Studies with a larger number of patients are required to identify the strong influencing factors for RIBI development.

FDG-PET/CT as prognostic factor and surveillance tool for postoperative radiation recurrence in locally advanced head and neck cancer.

PURPOSE: To evaluate the prognostic value of metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) on initial positron emission tomography-computed tomography (PET-CT) and investigate the clinical value of SUVmax for early detection of locoregional recurrent disease after postoperative radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A total of 100 patients with locally advanced HNSCC received primary tumor excision and neck dissection followed by adjuvant radiotherapy with or without chemotherapy. The MTV and SUVmax were measured from primary sites and neck nodes. The prognostic value of MTV and SUVmax were assessed using initial staging PET/CT (study A). Follow-up PET/CT scan available after postoperative concurrent chemoradiotherapy or radiotherapy were evaluated for the SUVmax value and correlated with locoregional recurrence (study B). A receiver operating characteristic (ROC) curve analysis was used to define a threshold value of SUVmax with the highest accuracy for recurrent disease assessment. RESULTS: High MTV (>41 mL) is negative prognostic factor for disease free survival (p = 0.041). Postradiation SUVmax was significantly correlated with locoregional recurrence (hazard ratio, 1.812; 95% confidence interval, 1.361 to 2.413; p < 0.001). A cut-off value of 5.38 from follow-up PET/CT was identified as having maximal accuracy for detecting locoregional recurrence by ROC analysis. CONCLUSION: MTV at staging work-up was significantly associated with disease free survival. The SUVmax value from follow-up PET/CT showed high diagnostic accuracy for the detection of locoregional recurrence in postoperatively irradiated HNSCC.

ERCC1 (excision repair cross-complementation group 1) expression as a predictor for response of neoadjuvant chemotherapy for FIGO stage 2B uterine cervix cancer.

OBJECTIVE: Platinum-based neoadjuvant chemotherapy for locally advanced cervical cancer has some benefits for patients responding to chemotherapy. However, no validated clinical or biologic predictor of response to this chemotherapy has been identified to date. METHODS: We employ immunohistochemical analysis to determine the expression patterns of the excision repair cross-complementation group1 (ERCC1) protein in pre-treatment cervical biopsy tissue. In total, 43 stage IIB patients had been enrolled in a previous etoposide and cisplatin neoadjuvant phase II clinical trial, allowing comparison of the effects of cisplatin-based neoadjuvant chemotherapy on response in relation to ERCC1 expression. RESULTS: Among the 43 patients studied, 34 (79.1%) were positive and 9 (20.9%) were negative for ERCC1. Response to chemotherapy (according to RECIST criteria) was observed in all patients with negative ERCC1 expression. In logistic regression analysis, ERCC1 negativity continued to be an independent predictor for responsiveness to neoadjuvant chemotherapy (p=0.021). Among the pretreatment factors, low ERCC1 expression was a significant prognostic factor of disease-free survival in multivariate analysis (p=0.046). CONCLUSIONS: The ERCC1 expression patterns in pretreatment specimens may thus facilitate the prediction of responses to cisplatin-based NAC. We propose that patients expressing low levels of ERCC1 derive the most benefit from cisplatin-based NAC.

The TGF-beta1 dynamics during radiation therapy and its correlation to symptomatic radiation pneumonitis in lung cancer patients.

BACKGROUND: The underlying molecular and cellular mechanisms of radiation pneumonitis (RP) are very complex. Several biological factors need to be considered together with the well known dosimetric parameters for understanding the molecular events in developing RP in lung cancer patients. The aim of this study was to correlate the variations of the cytokine levels in lung cancer patients during radiation therapy (RT) with the occurrence of symptomatic RP. METHODS: Thirty-four lung cancer patients who received three-dimensional conformal radiation therapy were evaluated prospectively. Serial blood samples before, at the beginning, in the middle of, at the end of RT and 2 and 4 weeks after RT were analyzed for IL-1alpha, IL-6, IL-10, TNF-alpha and TGF-beta1 by performing enzyme-linked immunosorbent assay. The predictive values of dosimetric factors for RP were evaluated, too. RESULTS: Overall, 8 patients (23.5%) had grade >or= 2 RP. By serial measurement of cytokines level, only the TGF-beta1 level showed a correlation to the symptomatic RP. None of the other cytokines, IL-1alpha, IL-6, IL-10 and TNF-alpha level was correlated with the risk of RP. The mean pretreatment TGF-beta1 level did not differ between RP and non-RP groups. However, during the period of radiation treatment, the TGF-beta1 level began to increase at the end of RT in the RP group and became significantly higher 4 weeks after RT (p = 0.007). Using an ANOVA model for repeated-measures, we found significant associations between the changes of TGF-beta1 during the time course of the RT and the risk of developing RP (p < 0.001). Most of the dosimetric factors showed a significant association with RP. CONCLUSION: Our results show that the changes of TGF-beta1 could be correlated with RP and the incorporation of the biological parameters into the dosimetric data could be useful for predicting symptomatic RP.