Seong Soo Shin

Fractionated stereotactic body radiation therapy for medically inoperable stage I lung cancer adjacent to central large bronchus.

PURPOSE To assess the body-framed stereotactic body radiation therapy (SBRT) results and toxicity for medically inoperable stage I lung cancer adjacent to central large bronchus and then compare the results with those of SBRT in peripheral lung tumor in the aspects of survival and SBRT-related pulmonary toxicities. MATERIALS From June 1999 to May 2006, 32 patients diagnosed as stage I, T1N0 or T2N0, resectable NSCLC were treated with body-frame based fractionated SBRT. Thirty-one patients had several medical problems conflicting surgical procedure. Stereotactic body frame was used for improving setup accuracy. Doses of 10-20 Gy per fraction were delivered to the planning target volume (PTV) up to a total dose of 40-60 Gy with three to four fractions on consecutive days. Centrally located tumor was defined as the tumor within 2 cm apart from large bronchial tree, and was subdivided into bronchial (main/lobar bronchus) and peribronchial (segmental or distal). RESULTS Median follow-up was 26.5 months. The 6-month major response rate, including complete or partial response, was 53.1%. One patient showed progressive disease 1 month after SBRT. The 1- and 2-year actuarial local tumor control rates were both 85.3%. Overall survival was 70.9% at 1 year and 38.5% at 2 years, and survival was not correlated with SBRT dose. Of 9 patients with centrally located tumors, three (33%) experienced Grades 3-5 pulmonary toxicities. Eight patients showed partial or complete bronchial stricture and secondary loss of normal lung volume. Median time to bronchial stricture was 20.5 months. Overall survival did not differ by tumor location. CONCLUSIONS SBRT in this fractionation should not be given to central lung tumors because it can cause the late major airway toxicities in some patients. More protracted hypofractionated treatment regimen may be more safe than that used usually in SBRT for central lung tumors.

High-dose Extended-Field Irradiation and High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Cervical Cancer With Positive Para-Aortic Lymph Nodes

PURPOSE To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. METHODS AND MATERIALS We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). RESULTS The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. CONCLUSION Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors

The aim of this study was to evaluate the treatment outcomes of stereotactic body radiation therapy for treating primary or metastatic thoracic tumors using a stereotactic body frame. Between January 1998 and February 2004, 101 lesions from 91 patients with thoracic tumors were prospectively reviewed. A dose of 10–12 Gy per fraction was given three to four times over consecutive days to a total dose of 30–48 Gy (median 40 Gy). The overall response rate was 82%, with 20 (22%) complete responses and 55 (60%) partial responses. The one- and two-year local progression free survival rates were 90% and 81%, respectively. The patients who received 48 Gy showed a better local tumor control than those who received less than 48 Gy (Fisher exact test; p = 0.004). No pulmonary complications greater than a RTOG toxicity criteria grade 2 were observed. The experience of stereotactic body frame based radiation therapy appears to be a safe and promising treatment modality for the local management of primary or metastatic lung tumors. The optimal total dose, fractionation schedule and treatment volume need to be determined after a further follow-up of these results.

Guiding curve based on the normal breathing as monitored by thermocouple for regular breathing

Adapting radiation fields to a moving target requires information continuously on the location of internal target by detecting it directly or indirectly. The aim of this study is to make the breathing regular effectively with minimizing stress to the patient. A system for regulating patients breath consists of a respiratory monitoring mask (ReMM), a thermocouple module, a screen, inner earphones, and a personal computer. A ReMM with thermocouple was developed previously to measure the patients respiration. A software was written in LabView 7.0 (National Instruments, TX), which acquires respiration signal and displays its pattern. Two curves are displayed on the screen: One is a curve indicating the patients current breathing pattern; the other is a guiding curve, which is iterated with one period of the patients normal breathing curve. The guiding curves were acquired for each volunteer before they breathed with guidance. Ten volunteers participated in this study to evaluate this system. A cycle of the representative guiding curve was acquired by monitoring each volunteers free breathing with ReMM and was then generated iteratively. The regularity was compared between a free breath curve and a guided breath curve by measuring standard deviations of amplitudes and periods of two groups of breathing. When the breathing was guided, the standard deviation of amplitudes and periods on average were reduced from 0.0029 to 0.00139 (arbitrary units) and from 0.359 s to 0.202 s, respectively. And the correlation coefficients between breathing curves and guiding curves were greater than 0.99 for all volunteers. The regularity was improved statistically when the guiding curve was used.

Concurrent chemoradiotherapy or radiotherapy alone for locally advanced cervical cancer in elderly women.

Aims and background To evaluate the efficacy and toxicity of concurrent chemoradiotherapy or radiotherapy alone in elderly patients with locally advanced cervical carcinoma (stage IB2-IVA). Methods and study design We retrospectively reviewed the medical records of 105 women aged ≥65 years who received radiotherapy (group I, n = 61) or concurrent chemoradiotherapy (group II, n = 44). Patients received a median dose of 76.4 Gy to point A, including 30-35 Gy of high-dose intracavity brachytherapy. The concurrent chemoradiotherapy group received platinum-based chemotherapy. Results The median follow-up was 65 months for surviving patients. There was no significant difference in compliance to radiotherapy between the two groups. Most acute toxicities were hematologic; acute hematologic and gastrointestinal toxicity were significantly more common in group II. Five-year overall survival and cancer-specific survival rates were, respectively, 53.5% and 66.6% in group I and 61.8% and 68.8% in group II. Performance status, comorbidity index, tumor size, and stage were independent prognostic factors for overall survival, whereas stage was the only prognostic factor for cancer-specific survival. Conclusions The analysis showed no benefit of concurrent chemoradiotherapy with respect to overall survival and cancer-specific survival in elderly women. A prospective study is needed to determine the role of concurrent chemoradiotherapy in this population. Free full text available at www.tumorionline.it

Feasibility and outcome of concurrent chemoradiotherapy for recurrent cervical carcinoma after initial surgery.

Aims and background The prognosis for recurrent cervical carcinoma following initial surgery is dismal even when aggressive radiotherapy or salvage surgery is used. We retrospectively reviewed hospital records to evaluate the efficacy and feasibility of concurrent chemoradiotherapy as a salvage treatment. Methods From 1999 to 2007, 47 patients received salvage chemoradiotherapy. Involved-field irradiation was delivered at a median dose of 64.8 Gy (range, 36–100.2), including brachytherapy boost in 10 patients. Pelvic re-irradiation was performed in 4 of the 12 women who had a previous history of pelvic radiotherapy. All but one patient received cisplatin-based concomitant chemotherapy during radiotherapy. Results The median overall follow-up period was 27 months and for surviving patients was 57 months. The interval between initial surgery and recurrence was 22 months (range, 4–203), and the median recurrent mass size was 4 cm (range, 0.5–11). In 34 patients, recurrent tumors were confined to the pelvis (21 central and 13 peripheral). Grade 3–4 acute hematologic toxicity was the most frequent toxicity and was observed in 29 (62%) women. Five-year actuarial cumulative incidence of severe gastrointestinal and genitourinary toxicity was 13% and 7%, respectively. Thirty-three patients (70%) showed a complete response and 9 (19%) a partial response following salvage chemoradiation. Five-year overall and disease-free survival rates were 44% and 41%, respectively. Conclusions Salvage chemoradiotherapy appears to be a feasible treatment option for women with recurrent cervical carcinoma following surgery. The treatment had a high salvage rate and acceptable late complication rate, despite being associated with substantial acute toxicity.

Treatment outcome of postoperative radiotherapy for retroperitoneal sarcoma

Purpose To evaluate the treatment outcome and prognostic factor after postoperative radiotherapy in retroperitoneal sarcoma. Materials and Methods Forty patients were treated with surgical resection and postoperative radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008. Treatment volume was judged by the location of initial tumor and surgical field, and 45-50 Gy of radiation was basically delivered and additional dose was considered to the high-risk area. Results The median follow-up period was 41.4 months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8% and disease free survival was 31.5%. The 5-year locoregional recurrence free survival was 61.9% and distant metastasis free survival was 50.6%. In univariate analysis, histologic type (p = 0.006) was the strongest prognostic factor for the OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also effect on the OS. Histologic type (p = 0.004) was unique significant prognostic factor for the actuarial local control. Conclusion Retroperitoneal sarcoma still remains as a poor prognostic disease despite the combined modality treatment including surgery and postoperative radiotherapy. Selective dose-escalation of radiotherapy or combination of effective chemotherapeutic agent must be considered to improve the treatment result especially for the histopathologic type showing poor prognosis.

Long-term outcomes of concomitant chemoradiotherapy incorporating high-dose-rate brachytherapy to treat locally advanced cervical cancer.

AIM AND BACKGROUND We reviewed the long-term clinical outcomes of patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT) incorporating high-dose-rate (HDR) intracavitary brachytherapy (ICBT) in terms of toxicity, local control and survival rates. In addition, we identified prognostic factors for overall and disease-free survival. METHODS AND STUDY DESIGN . Two hundred and nine patients with stage IB2-IVA cervical cancer underwent curative cisplatin-based CCRT plus HDR ICBT. Women with stage IB2-IIB disease were given 41.4 Gy of external radiotherapy followed by 35 Gy (in 7 fractions) of ICBT. Women with stage IIIA-IVA were given 50.4 Gy followed by 30 Gy (in 6 fractions) of ICBT. Patients with parametrial disease or pelvic lymphadenopathy were given parametrial boosts via external beam radiation at a dose of up to 65 Gy to thickened and 60 Gy to unthickened parametrial regions. RESULTS One hundred and thirty (62%) patients experienced acute grade 3-4 hematological toxicities and 11 (5%) patients had late grade 3 gastrointestinal or genitourinary complications. Complete responses occurred in 168 (80%) women as determined by clinical and imaging studies. The median follow-up period was 52 months for surviving patients and the 5-year overall and disease-free survival rates were 74% and 67%, respectively. Multivariate analysis indicated that tumor size and paraaortic lymph node involvement were prognostically significant in terms of overall survival, and that tumor diameter was a significant prognostic factor and pelvic lymph node status a marginally significant prognostic factor for disease-free survival. CONCLUSIONS Patients treated with our current HDR ICBT protocol have acceptably low late complication rates and local control and survival rates comparable to those reported in other studies. Tumor diameter was an important prognostic factor in terms of both overall and disease-free survival, emphasizing the need for modern ICBT methodologies.

Prospective Phase II Study of Preoperative Chemoradiation with Capecitabine in Locally Advanced Rectal Cancer

PURPOSE Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer. MATERIALS AND METHODS A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m(2) capecitabine in two portions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation. RESULTS Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed. CONCLUSION Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.

Hypofractionated intensity-modulated radiotherapy using simultaneous integrated boost technique with concurrent and adjuvant temozolomide for glioblastoma.

AIMS AND BACKGROUND We assessed the therapeutic efficacy of combined hypofractionated intensity-modulated radiotherapy with temozolomide in patients with primary glioblastoma. METHODS AND STUDY DESIGN Thirty-nine patients with histologically confirmed glioblastoma were accrued. Using the simultaneous integrated boost technique, a dose of 50 Gy in 5-Gy fractions was applied to the gross tumor volume, together with 40 Gy in 4-Gy fractions and 30 Gy in 3-Gy fractions to the 1- and 2-cm margins from the gross tumor volume, respectively. Patients were also treated with concurrent temozolomide during intensity-modulated radiotherapy, followed by six cycles of adjuvant temozolomide. RESULTS Median follow-up was 16.8 months (range, 4.3-54.3). Tumor progression was observed in 28 patients (71.8%), and the median time to progression was 6.8 months. Median survival was 16.8 months, and it was affected significantly by the extent of surgery. During adjuvant temozolomide treatment, 3 patients (9.7%) developed grade 3-4 hematologic or hepatic toxicity. Radiation necrosis developed in 7 patients (17.9%) and massive necrosis, requiring emergency surgery, in 1 patient (2.6%). CONCLUSIONS The regimen of hypofractionated intensity-modulated radiotherapy with temozolomide showed a relatively good outcome in patients with glioblastoma. Further studies are required to define the optimal fraction size for glioblastoma using this highly sophisticated radiation technique.