Serdar Ozkok

High dose rate endobronchial brachytherapy in the management of lung cancer: Response and toxicity evaluation in 158 patients

The aim of this study was to evaluate the symptomatic and endoscopic responses as well as the toxicities in 158 patients with endobronchial lung cancer treated with high dose rate endobronchial brachytherapy (HDR-EB). Forty-three patients with stage III NSCLC were treated with 60Gy external beam radiotherapy (ERT) and three applications of 5Gy each of HDR-EB (group A). Seventy-four patients who did not receive previous RT were treated with 30Gy ERT and two applications of 7.5Gy HDR-EB with palliative intent (group B). Forty-one patients with recurrent tumor who were irradiated previously were treated with three applications of 7.5Gy HDR-EB, with palliative intent (group C). In group A, bronchoscopic complete (CR) and overall response rates (ORR) were 67% and 86%, respectively. Symptomatic improvement was obtained in 58% of patients with cough, 77% of patients with dyspnea and 100% of patients with hemoptysis. Two and 5-year survival rates were 25.5% and 9.5%, respectively and the median survival time (MST) was 11 months. In group B, the bronchoscopic CR and ORR were 39% and 77%, respectively and 28% and 72% in group C. The symptomatic response rates were 57% and 55% for cough, 90% and 78% for dyspnea and 94% and 77% for hemoptysis, with a MST of 7 and 6 months in Groups B and C, respectively. Eighteen patients (11%) died of fatal hemoptysis (FH) with the median time to this event of 7 months. Treatment intent (p<0.001), total BED (p<0.001) and the number of HDR-EB fractions (p<0.001) were significant prognostic factors for FH. HDR-EB provides effective palliation in relieving the symptoms of patients with endobronchial lung cancer, however, there is a risk of developing FH that is associated with a high BED and multiple HDR-EB applications.

High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer.

INTRODUCTION A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients. MATERIALS AND METHODS Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival. RESULTS Therapy regimen was found to be very effective for the palliation of major symptoms, palliation rates were 42.8% for cough, 95.2% for hemoptysis, 88.2% for chest pain and 80.0% for dyspnea. There was a 76.7% tumor response (53.3% complete, 23.3% partial) verified by chest CT scans and bronchoscopy. However, median locoregional disease free survival was 9+/-4 months (95% CI: 1-17) and it was only 9.6% at 5 years. Major side effects were radiation bronchitis (70.0%), esophagitis (6.6%) in the acute period and bronchial fibrosis (25%), esophagial fibrosis (12.5%) and fatal hemoptysis (10.5%) in the late period. Median survival was 11+/-4 months (95% CI: 4-18),and 5-year actuarial survival was 10%. Locoregional disease free survival (P=0.008) and the overall survival was longer (P<0.001) in the patients younger than 60, survival was also improved in the patients with complete response (P=0.019). There were no major complications during catheterisation; early side effects were quite tolerable but severe late complications were around 10%. CONCLUSIONS It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response, however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients.

Postoperative Radiotherapy in the Management of Resected Non–Small-Cell Lung Carcinoma: 10 Years' Experience in a Single Institute

PURPOSE This study reports the long term outcomes of postoperative radiotherapy in patients with resection for non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS A total of 98 patients with resected NSCLC who received postoperative radiotherapy (PORT) between January 1994 and December 2004 were retrospectively analyzed. The most frequently performed surgical procedure was lobectomy (59 patients), followed by pneumonectomy (25), wedge resection (8), and bilobectomy (6). Postoperative radiotherapy was delivered as an adjuvant treatment in 71 patients, after a wedge resection in 8 patients, and after an R1 resection in 19 patients. The PORT was administered using a Co-60 source in 86 patients and 6-MV photons in 12 patients. A Kaplan-Meier estimate of overall survival, locoregional control, and distant metastasis-free survival were calculated. RESULTS Stages included I (n =13), II (n = 50), IIIA (n = 29), and IIIB (n = 6). After a median follow-up of 52 months median survival was 61 months. The 5-year overall survival, locoregional control, and distant metastasis-free survival rates for the whole group were 50%, 78%, and 55% respectively. The RT dose, Karnofsky performance status, age, lateralization of the tumor, and pneumonectomy were independent prognostic factors for OAS; anemia and the number of involved lymph nodes were independent prognostic factors for LC. CONCLUSIONS Doses of PORT of greater than 54 Gy were associated with higher death rate in patients with left-sided tumor, which may indicate a risk of radiation-induced cardiac mortality.

Phase II Study of Loading-Dose Ibandronate Treatment in Patients with Breast Cancer and Bone Metastases Suffering from Moderate to Severe Pain

Background: The aim of this study was to determine the efficacy and safety of loading-dose intravenous (i.v.) ibandronate in women with breast cancer and bone metastases. Patients and Methods: In this prospective, phase II, open-label study, 13 women with breast cancer, bone metastases, and moderate/severe bone pain received ibandronate 6 mg/day (i.v. loading-dose 15 min infusion over 3 consecutive days) with follow-up until day 14. Endpoints included pain response (primary), duration until pain response, analgesic use, Karnofsky index, safety (including hematologic, biochemical, and urine examinations), and adverse events. Results: Pain intensity decreased on days 7 and 14 versus day 1 (mean visual analogue scale score: 3.2 ± 2.2 and 3.0 ± 2.1 versus 6.1 ± 0.9, respectively; p < 0.01 for both). Mean time to pain response was 8.2 ± 3.3 days. Mean rate of analgesic use decreased (69.2%, 16.7% and 15.4% on days 1, 7 and 14, respectively). Mean Karnofsky index score increased (80.8 ± 13.1 and 80.8 ± 13.2, on days 7 and 14 versus 77.7 ± 11.7 on day 1; p < 0.05 on both days). Conclusion: Bone pain and analgesic use decreased in women with breast cancer and bone metastases following loadingdose i.v. ibandronate which was well-tolerated with no renal safety concerns.

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results.

AIMS AND BACKGROUND There has been a trend to replace cisplatin with carboplatin in the treatment of small-cell lung carcinoma. The goal of the present study was to determine the efficacy of carboplatin and etoposide followed by thoracic radiotherapy in patients with previously untreated limited disease small-cell lung carcinoma. METHODS From February 2001 to March 2007, 47 patients with limited disease small-cell lung cancer were enrolled in the study. Etoposide, 100 mg/m2, was administrated intravenously on days 1-3 in combination with carboplatin, AUC 6, on day 1 every 21 days for 6 cycles. In cases considered to have non-progressive disease following induction chemotherapy, thoracic radiotherapy was given with in a once daily fraction of 2.0 Gy, 5/wk, up to 50-60 Gy. RESULTS Forty-one patients were evaluated. Median age was 62 (range, 40-78), 88% of patients were male. ECOG PS was 0-1 in 38 patients. Seven of the 41 patients (17.5%) had pleural effusion (one malignant) and 7 patients (17.5%) had involved supraclavicular lymph nodes. Ninety percent of patients had elevated serum lactate dehydrogenase levels. Median follow-up was 13.5 mo. A total of 209 cycles of chemotherapy was administered (median, 6; range, 1-6). Thoracic irradiation was given to 33 patients. The overall response rate to combined modality on an intention-to-treat basis was 73%. Median survival time was 13.7 months (95% CI, 10.3-17.1), and median progression-free survival was 9.5 months (95% CI, 8.6-10.4). Two- and four-year overall survival was 23% and 7%, respectively. Grade 3-4 neutropenia and leukopenia were the most common adverse events and occurred in 46.0% and 24.0% of the patients, respectively. Six (14%) patients experienced febrile neutropenia. Three patients (7%) died of sepsis and neutropenic fever. Non-hematological toxicities were mild. CONCLUSIONS Carboplatin and etoposide chemotherapy followed by thoracic radiotherapy in LD-SCLC appears to be unsatisfactory.

The role of delineation education programs for improving interobserver variability in target volume delineation in gastric cancer

OBJECTIVE To assess whether delineation courses for radiation oncologists improve interobserver variability in target volume delineation for post-operative gastric cancer radiotherapy planning. METHODS 29 radiation oncologists delineated target volumes in a gastric cancer patient. An experienced radiation oncologist lectured about delineation based on contouring atlas and delineation recommendations. After the course, the radiation oncologists, blinded to the previous delineation, provided delineation for the same patient. RESULTS The difference between delineated volumes and reference volumes for pre- and post-course clinical target volume (CTV) were 19.8% (-42.4 to 70.6%) and 12.3% (-12.0 to 27.3%) (p = 0.26), respectively. The planning target volume (PTV) differences pre- and post-course according to the reference volume were 20.5% (-40.7 to 93.7%) and 13.1% (-10.6 to 29.5%) (p = 0.30), respectively. The concordance volumes between the pre- and post-course CTVs and PTVs were 467.1 ± 89.2 vs 597.7 ± 54.6 cm3 (p < 0.001) and 738.6 ± 135.1 vs 893.2 ± 144.6 cm3 (p < 0.001), respectively. Minimum and maximum observer variations were seen at the cranial part and splenic hilus and at the caudal part of the CTV. The kappa indices compared with the reference contouring at pre- and post-course delineations were 0.68 and 0.82, respectively. CONCLUSION The delineation course improved interobserver variability for gastric cancer. However, impact of target volume changes on toxicity and local control should be evaluated for further studies. Advances in knowledge: This study demonstrated that a delineation course based on current recommendations helped physicians delineate smaller and more homogeneous target volumes. Better target volume delineation allows proper target volume irradiation and preventing unnecessary normal tissue irradiation.

Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer: Short versus long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer

The optimal timing of surgery following preoperative chemoradiotherapy (CRT) is controversial. This trial aimed to compare pathological complete response (pCR) rates obtained after an interval of 8 weeks or less versus more than 8 weeks.

Practice patterns for oropharyngeal cancer in radiation oncology centers of Turkey.

Aims and Background The aim of the study was to review the current clinical practices of radiation oncologists involved in the treatment of oropharyngeal cancer. Methods and Study Design The daily practices of radiation oncology centers for patients diagnosed with oropharyngeal cancer in 2010 were evaluated by a two-part questionnaire that separately assessed the information of the participating center and the charts of the treated patients. Results A total of 22 centers participated in the study, and 105 oropharyngeal cancer patients reported for our review. The use of positron emission tomography was a common practice in staging and radiotherapy planning. Multidisciplinary head and neck cancer clinics were available in 14 (64%) centers and were absent in 8 centers. Thirty-six of the 105 patients were not evaluated by a multidisciplinary clinic before the initiation of therapy, and adjuvant radiotherapy administration was found to be higher in this group. Percutaneous endoscopic gastrostomy tube placement was not a routine practice in any of the centers. Seventy-five patients received chemotherapy – 46 concurrently with radiotherapy and 29 as induction chemotherapy. Two centers administered conventional radiotherapy alone, 20 centers conformal radiotherapy, and 7 centers were able to provide intensity-modulated radiotherapy. Conclusions Across all the centers there were small differences in the pretreatment evaluation of patients with oropharyngeal cancer. The greatest difference was in the technical delivery of radiation, with most of the centers using conformal radiotherapy despite the increasing availability of intensity-modulated radiotherapy. The use of chemotherapy has more readily adopted the current international standards in the treatment of oropharyngeal cancer.

Postoperative gemcitabine alone and concurrent with radiation therapy in locally advanced pancreatic carcinoma.

Aims and background To evaluate the treatment results of gemcitabine alone and concurrent with radiotherapy after R0/R1 resection of locally advanced pancreatic cancer. Methods and study design From 1999 to 2005, 55 patients with stage II resected pancreatic cancer treated with gemcitabine-based radiochemotherapy were retrospectively evaluated. Initially, one cycle of induction gemcitabine was administered and followed by weekly gemcitabine concurrent with radiotherapy. After the completion of radiochemotherapy, patients received 3 additional courses of gemcitabine. Results Thirteen patients were stage IIA and 42 were stage IIB. Forty-six patients (83.6%) had R0 and 9 patients (16.4%) had R1 resection. All of the patients received induction chemotherapy and radiotherapy, all but 3 received concurrent radiochemotherapy, and 46 (84%) patients received maintenance chemotherapy. During induction, concurrent and maintenance phases of the protocol, 11%, 13.5% and 19.5% of the patients had at least one ≥grade 3 toxicity, respectively. Within a median 47 months (range, 34–105) of follow-up, 4 (7.3%) patients had isolated local recurrence, 5 (9%) patients had local recurrence and distant metastases, and 27 (49%) had only distant metastases. Median disease-free survival and overall survival were 13 (range, 4-105) and 19 months (range, 6-105), respectively. In multivariate analysis, nodal stage, AJCC stage and number of lymph nodes dissected were the significant factors affecting disease-free survival whereas Karnofsky performance status was the only significant factor for overall survival. Conclusions The prognosis for pancreatic cancer remains poor despite adjuvant radiochemotherapy. More aggressive treatments should be considered in patients with unfavorable prognostic factors.

P1-211: Combined modality treatment approach in small cell lung cancer: results of 83 patients

Prognostic analysis of Small Cell Lung Cancer (SCLC) treated with postoperative chemotherapy Shi, Yuankai1 Wang, Huijie2 Zhang, Xiangru2 Sun, Yan1 1 ASCO, Beijing, China 2 CSCO, Beijing, China Background: Several pretreatment characteristics in patients with small-cell lung cancer (SCLC) have been associated with meaningful differences in survival. In patients with limited-stage disease,good PS, female gender, age younger than 70 years, normal LDH,and stage I disease are associated with a more favorable prognosis.In patients with extensive-stage disease, normal LDH and a single metastatic site are favorable prognostic factors. Recently our study revealed that LD stage SCLC treated with multidisciplinary therapy including surgery had beter survival outcome. We try to explore clinical and pathologic factors that affect the prognosis of SCLC treated with postoperative chemotherapy in this retrospective study. Methods: From Jan 1999 to Dec 2004, 111 patients treated with postoperative chemotherapy in our single institute were reviewed retrospectively. Postoperative chemotherapy including platin-contained or non-platin contained standard regime: CE (Carboplatin AUC 5 d1 Etoposide 100mg/m2 d1-5,q3w), EP (cisplatin 60-80/mg2 divided into 3 days/Etoposide 100mg/m2 d1-5,q3w), CAO (Cyclophosphamide 1000mg/m2 d1/Doxorubicin 45 mg/m2 d1/Vincristine 2mg d1, q3w), CAP (Cyclophosphamide 1000mg/m2 d1/Doxorubicin 45 mg/m 2 d1/ cisplatin 60-80/mg2 divided into 3 days, q3w). Postoperative chemotherapy range from 1 to 13 cycles, median cycles 6. Prognostic analysis included clinical and pathologic factors related. Results: The overall median survival time (MST) of SCLC treat with postoperative chemotherapy is 38 months, the 1-,3-,5 year survival rate was 85.6%, 50.6%, 38.7%,respectively. The significant prognostic factors for survival in these series of patients were early stage, female, no lymphnode metastasis, no lymphovascular invasion (P=0.001), and more chemotherapy cycles (p=0.032). According to TNM stage system, the MST of stage IA and IB were not reached,for stage IIB, IIIA and IIIB was 52 months, 24 months and 13 months (P=0.006), respectively. MST of male and female were 35 months and not reached (P=0.042); lymphnode metastasis and no lymphnode metastasis were 26 months and not reached (P=0.001), lymphovascular invasion and no lymphovascular invasion were 15 and 51 months, and MST of received 1-3,4-6 and more than 6 chemotherapy cycles were 26,40months and not reached. For 66 pts with stage III, the MST of postoperative chemotherapy and postoperative chemoradiotherapy were 20 and 40 months, 5 years survival rate were 26.1% and 45.3% (P=0.071). Cox’s multivariate analysis identified sex (P=0.011), lymphovascular invasion (P=0.002), TNM stage (P=0.019), combined radiotherapy (P=0.030) and more chemotherapy cycles (P=0.009) as independent prognostic variables. Conclusion: For SCLC treated with postoperative chemotherapy, TNM stage system was an important prognostic factor, sex, lymphovascular invasion,combined radiotherapy and chemotherapy cycles also affect overall survival time. P1-211 SCLC: Combined Modality Therapy Posters, Mon, Sept 3