Concurrent Chemotherapy and Proton Beam Therapy for Esophageal Cancer

Proceedings of the 51st Annual ASTRO Meeting

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Does Concurrent Chemoradiotherapy Compromise the Delivery of Subsequent Sequential Gemcitabine in Locally Advanced Pancreatic Cancer?

Z. Symon1, T. Rabin1, Y. Kundel2, I. Gluck1, I. Wolf1, D. Aderka1, M. Ben-David1, R. Catane1, M. Pfeffer1 1

Sheba Medical Center, Ramat Gan 52621, Israel, 2Davidoff Cancer Center, Petach Tikva, Israel

Purpose/Objective(s): Gemcitabine has become the mainstay of chemotherapy in the treatment of pancreatic cancer. Whether concurrent chemoradiotherapy is detrimental or provides any benefit over treatment with gemcitabine alone in the treatment of locally advanced pancreatic cancer is controversial. The aim of this study is to determine whether concurrent chemoradiation compromises the ability to deliver sequential chemotherapy in clinical practice. Materials/Methods: Pharmacy and medical records of 42 consecutive patients treated with conformal 3-D radiation and concurrent gemcitabine for locally advanced pancreatic cancer were examined. Gemcitabine was given intravenously at 1000 mg/m2 weekly during radiation, and continued weekly at 1000 mg/m2 following radiation for 3 weeks on, one week off until disease progression. A subset of six patients had received 3 or more weekly cycles of gemcitabine prior to radiation therapy (mean of 8.5 cycles, range 3-17) The gross tumor volume (GTV) was defined as the primary tumor identifiable on CT scan, including enlarged nodes greater than 1 cm. Clinically uninvolved regional lymph node basins were not included. The clinical target volume (CTV) was the GTV plus 0.5 cm, or the tumor bed and was extended by an additional 0.5 cm for the PTV. Radiation dose was either 15 fractions of 2.4 Gy or 25 fractions of 1.8Gy. Results: During radiotherapy, 34 patients (79%) received weekly gemcitabine as prescribed and 8 patients received fewer cycles. Following radiation, 22 patients (51.1%) continued to receive sequential chemotherapy for at least 3 cycles (mean of 9.5 cycles range 3-36). The median absolute dose of gemcitabine was 1749 mg/ cycle for patients receiving chemotherapy prior to chemo-radiation vs. 1990 mg/cycle for patients who received subsequent chemotherapy following chemo-radiation (p = ns). The median survival was 12.4 months. Grade III-IV gastrointestinal toxicity was observed in 6 patients (17.6%) with 2 patients requiring surgery for small bowel obstruction. One patient developed grade III thrombocytopenia after 15 cycles of gemcitabine. Conclusions: The delivery of sequential weekly gemcitabine until disease progression, following reduced volume conformal chemo-radiation, is feasible and tolerable. The median survival in this cohort was comparable or superior to that reported in contemporary studies. Concurrent conformal chemo-radiation is a valid treatment option and does not compromise the tolerability of subsequent sequential chemotherapy. Author Disclosure: Z. Symon, None; T. Rabin, None; Y. Kundel, None; I. Gluck, None; I. Wolf, None; D. Aderka, None; M. BenDavid, None; R. Catane, None; M. Pfeffer, None.

2242

Analysis of the Factors Which Affect on the Nodal Area Irradiation for Esophageal Cancer: Results of the Patterns of Care Study in Japan

M. Kenjo1, Y. Murakami1, T. Tomita2, S. Saito2, H. Numasaki2, T. Teshima2, M. Mitsumori3 1

Hiroshima University, Hiroshima, Japan, 2Osaka University, Osaka, Japan, 3Kyoto University, Kyoto, Japan

Purpose/Objective(s): The benefit of the prophylactic nodal irradiation for esophageal cancer is unknown. The purpose of this study is to reveal the executing rates and to investigate the factors which affect on the regional radiotherapy (RT) for esophageal cancer patients. This study is based on data of the two Patterns of Care Studies in Japan (1999-2001 and 2003-2005). Materials/Methods: Detail records of 651 patients with thoracic esophageal cancer were accumulated from nationwide 109 facilities including academic (55) and nonacademic (54) institutions using the two-stage cluster random sampling. Inclusion criteria are as follows; thoracic esophageal cancer, Karnofsky Performance Status (KPS) score .=60, without distant metastasis, without prior or concurrent malignancies, treated with external beam radiotherapy and without surgery. Median age was 70 years and median KPS score was 80. 98% had squamous cell carcinoma histology. Main primary tumor was located on upper-thoracic esophagus (Ut) in 19% of the patients, mid-thoracic (Mt) in 55% and lower-thoracic (Lt) in 23%. 19% had T1 disease, 49% had T2-3 and 26 % had T4. 51% had clinically N1 disease. Length of main tumor was 5cm in 63%. 63% received chemotherapy. 56% of the patients received 3-dimmentional (3-D) RT planning and 70% were treated with multi-leaf-collimator (MLC) equipped machine. Results: Median longitudinal field size of RT was 18cm. Supraclavicular, mediastinal and upper abdominal nodal area irradiation were done in 28%, 77% and 27% of the all patients, Each nodal area RT was done in 61%, 90%, 12% of the patients who had primary site in Ut, respectively, in 23%, 81%, 24% of Mt patients and in 14%, 62%, 45% in Lt. The ratios of supraclavicular RT for Mt were 36% of the patients = 75 y/o (p\0.01); 17% of T1 patients, 23% of T2-3 and 28% of T4 (p = 0.15); 14% of N0 patients and 34% of N1 (p \ 0.01); 28% of the patients treated in academic institutions and 18% in nonacademic (p = 0.02); 29% of the patients who received 3-D planning and 16% of 2-D planning (p \ 0.01); 29% of the patients who used MLC and 17% of fixed block (p = 0.04). The ratios of upper abdominal RT for Lt were 60% of the patients = 75 y/o (p \ 0.01); 18% of T1 patients, 52% of T2-3 and 52% of T4 (p = 0.01); 29% of N0 patients and 60% of N1 (p \ 0.01); 48% of the patients treated in academic institutions and 42% in nonacademic (p = 0.44); 57% of the patients who received 3-D planning and 29% of 2-D planning (p \ 0.01); 56% of the patients who used MLC and 38% of fixed block (p = 0.06). 83% of the all patients completed planned treatment. Conclusions: This study revealed that the patients’ age affected on the decision making of nodal RT. Clinical target volume settings might be influenced not only by the tumor status but also by the RT planning processes. Author Disclosure: M. Kenjo, None; Y. Murakami, None; T. Tomita, None; S. Saito, None; H. Numasaki, None; T. Teshima, None; M. Mitsumori, None.

2243

Concurrent Chemotherapy and Proton Beam Therapy for Esophageal Cancer

G. Xiaomao1, Z. X. Liao2, R. Komaki2, H. Wen2, J. Y. Chang2, M. O’Reilly2, M. Jeter2, K. Bucci2, J. Ajani2, J. D. Cox2 1

Fudan University, Cancer Hospital, Shanghai, China, 2The University of Texas M. D. Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Concurrent chemoradiation with or without surgery is the treatment of choice for patients with esophageal cancer. Proton beam therapy has been used as a single modality for inoperable patients. However, there has no experience

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I. J. Radiation Oncology d Biology d Physics

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Volume 75, Number 3, Supplement, 2009

in using proton concurrently with chemotherapy for esophageal cancer. The purpose of the study is to report the preliminary results of concurrent chemotherapy and proton beam therapy compared with intensity modulated radiation for locally advanced esophageal cancer. Materials/Methods: We treated 53 and 18 esophageal cancer patients with either intensity modulated radiation (IMRT) or proton beam therapy (PBT) between 2004 and 2008. Patient-, disease, treatment parameters, and toxicity were compared between the two groups. Kaplan-Meier Survival estimates on overall survival (OS) and disease specific survival (DSS) was calculated from the end day of radiotherapy. The differences between the groups were tested using Logrank analysis. Results: There was no difference in sex, gender, histology, stage, smoking status between the groups. The patients in PCT group were older (p = 0.0084), all consumed alcohol (p = 0.002), had better performance status (0.005), and more N1 disease (p = 0.044). Median IMRT dose was 50.4 Gy (range, 45-66Gy), and median PCT dose was 50.4 (range 36-54) Cobalt Gray Equivalent (CGE). All patients had concurrent chemotherapy. Treatment related esophagitis, pneumonitis, and dermatitis were low in either group. No statistically significant differences exist in treatment related esophagitis, pneumonitis, dermatitis, or the rates of OS and DSS between the two groups. Conclusions: Our preliminary results show that PCT treatment with concurrent chemotherapy for esophageal cancer is feasible. Additional analyses on metabolic and pathological response in patients treated in the 2 groups are ongoing. Author Disclosure: G. Xiaomao, None; Z.X. Liao, None; R. Komaki, None; H. Wen, None; J.Y. Chang, None; M. O’Reilly, None; M. Jeter, None; K. Bucci, None; J. Ajani, None; J.D. Cox, None.

2244

Radiotherapy and Chemoradiation for Advanced Inoperable Esophageal Cancer

R. Semrau, S. L. Herzog, M. Kocher, R. P. Mueller University of Cologne, Koeln, Germany Purpose/Objective(s): Patients suffering from esophageal cancer mostly present in advanced stages with an unfavorable prognosis. In this large uni-institutional survey efficacy and toxicity of radiotherapy and chemoradiation for advanced inoperable esophageal cancer patients was studied. Materials/Methods: Patients with inoperable adenocarcinoma (AC) or squamus cell carcinoma (SCC) of the esophagus treated with radiotherapy or chemoradiation at University of Cologne between 1995 and 2005 were included. Total dose of radiotherapy was 63Gy (5x1.8Gy weekly). Chemotherapy consisted of Cisplatin (20 mg/m2; d1-5 and d29-33) and 5FU (650-1000mg/m2; d1-5 and d29-33). Treatment toxicity was documented according to CTC v.3.0 criteria. Results: 204 patients with advanced SCC (79%) or AC (21%) of the esophagus were treated (12.3% T1/2; 60,8% T3; 22.1% T4-tumors). 19.6% were N0 and 67.6% N+. The 2-year overall survival probability (OS) was 22% and 15% for SCC-and ACpatient (p = 0.22). The 2-year probability of progression free survival (PFS) was 15 % for SCC and 5 % for AC, respectively (p = 0.041). The 2-year OS for cN0-patients was 41% and for cN+/x patients 15% (p = 0.009). Among those patients being nodal negative the patients having a tumor stage T1 or T2 had a 2-year OS-probability of 50 % compared to 39 % with T3 tumors (p = 0.594). Patients with a T3N0 stage had a 39 % 2-year-OS compared to 15.5 % with T3N+ tumors (p = 0.76). 117 patients received chemotherapy and had a higher 2-year OS compared to those 87 patients that did not (28 % and 11 % respectively; p = 0.002). Female patients had a significantly better 2-year OS (26%) compared with male patients (19% p = 0.035). 43.6% of the patients treated suffered from leucopenia of any grade, (6.9% grade IV). Anemia was observed in 71,5%, with only one grade IV (0.5%). Thrombocytopenia of any grade was seen in 33.3% of patients (2.5% grade IV). Other treatment related toxicities were dermatitis in 65.7% of all cases (1% grade III) and gastrointestinal symptoms in 58,3% (0.5% grade IV). Of all patients 55.4% had to be hospitalized during treatment due to toxicities. There were 6 treatment-related deaths (2.9%). Conclusions: The study population consisted of inoperable patients with advanced tumors (mainly with SCC). SCC-patients had a better prognosis (PFS) than AC-patients. The nodal status is a major prognostic factor for OS in patients with inoperable esophageal cancer. Concurrent chemotherapy positively influenced survival. Treatment toxicity is severe and requires special care including inpatient treatment for patients with lower performance status. Author Disclosure: R. Semrau, None; S.L. Herzog, None; M. Kocher, None; R.P. Mueller, None.

2245

Clinical Significance of p53, pRb, hMLH1 and MDM2 Expression Prior to Preoperative Chemoradiotherapy for Patients with Rectal Cancer

T. K. Nam1, J. S. Lee2, H. R. Kim3, Y. J. Kim3, B. S. Nah1, W. K. Chung1, S. J. Ahn1, J. Y. Song1, M. S. Yoon1, J. U. Jeong1 1 Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, Republic of Korea, 2Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea, 3Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea Purpose/Objective(s): To better define the potential prognostic and predictive role of tumor biomarkers, we evaluated p53, pRb, hMLH1 (a component of the DNA mismatch repair system) and MDM2 (murine double minute 2 oncogene) expression before preoperative chemoradiotherapy (CRT) in patients with rectal cancer and attempted to determine any correlation with treatment outcome. There have been few reports regarding the positive significance of these biomarkers, especially for the use of preoperative CRT for rectal cancer. Materials/Methods: Between March 2000 and May 2007, 45 patients with rectal cancer who had available pretreatment biopsy tissue and who had undergone preoperative CRT were enrolled in this study. Preoperative CRT consisted of a median dose of 50.4 Gy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed at a median seven weeks after CRT. The criteria for