Chronological Analysis of Acute Hematological Outcomes after Proton and Photon Beam Craniospinal Irradiation in Pediatric Brain Tumors.

PURPOSE: This study aimed to compare the early hematological dynamics and acute toxicities between proton beam craniospinal irradiation (PrCSI) and photon beam craniospinal irradiation (PhCSI) for pediatric brain tumors. MATERIALS AND METHODS: We retrospectively reviewed patients with pediatric brain tumors who received craniospinal irradiation (CSI). The average change in hemoglobin levels (ΔHbavg), absolute lymphocyte counts (ΔALCavg), and platelet counts (ΔPLTavg) from baseline values was evaluated and compared between the PrCSI and PhCSI groups at 1 and 2 weeks after the initiation of CSI, 1 week before and at the end of radiotherapy, and 3-4 weeks after the completion of radiotherapy using t test and mixed-model analysis. RESULTS: The PrCSI and PhCSI groups consisted of 36 and 30 patients, respectively. There were no significant differences in ΔHbavg between the two groups at any timepoint. However, ΔALCavg and ΔPLTavg were significantly lower in the PhCSI group than in PrCSI group at every timepoint, demonstrating that PrCSI resulted in a significantly lower rate of decline and better recovery of absolute lymphocyte and platelet counts. The rate of grade 3 acute anemia was significantly lower in the PrCSI group than in in the PhCSI group. CONCLUSION: PrCSI showed a lower rate of decline and better recovery of absolute lymphocyte and platelet counts than PhCSI in the CSI for pediatric brain tumors. Grade 3 acute anemia was significantly less frequent in the PrCSI group than in the PhCSI group. Further large-scale studies are warranted to confirm these results.

High-dose thoracic radiation therapy at 3.0 Gy/fraction in inoperable stage I/II non-small cell lung cancer.

OBJECTIVE: High-dose thoracic radiation therapy (HDTRT) alone has been an alternative to surgery in stage I/II non-small cell lung cancer patients with medical co-morbidities and/or poor performance status. Here, we report on the outcome and safety of HDTRT at 3.0 Gy per fraction for reduced treatment duration. METHODS: HDTRT alone at 3.0 Gy per fraction was given to 35 patients (22 at stage I and 13 at stage II). The median age was 73 years old and 14 patients had ECOG performance above 2. The median radiation dose to the primary lesion was 60 (54-66) Gy over 27 (23-38) days, and the dose to the mediastinum was individualized. RESULTS: After the median follow-up of 24 (3-72) months, local in-field progression developed in 11 patients (31.4%) and distant metastases in 14 (40.0%). The median survival period and the 3- and 5-year overall survival (OS) rates for all patients were 24.0 (95% CI: 13.57-34.43) months, 31.4 and 11.2%. Intercurrent deaths were observed in 11 patients. Treatment-related acute and subacute morbidities were observed in 20 patients (57.1%); however, there was neither treatment interruption nor long-term morbidity. CONCLUSIONS: On the basis of the above observations, we achieved treatment outcomes comparable with those of conventional protracted fractionation schedules at considerably shorter duration and lower cost by HDTRT at 3.0 Gy per fraction.

Phase II study of consolidation chemotherapy after concurrent chemoradiation in cervical cancer: preliminary results.

PURPOSE: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. METHODS AND MATERIALS: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m(2) (Day 1) and 5-fluorouracil 1000 mg/m(2) (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. RESULTS: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). CONCLUSIONS: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile.

Six fractions per week of external beam radiotherapy and high-dose-rate brachytherapy for carcinoma of the uterine cervix: A phase I/II study.

PURPOSE: This study evaluated the treatment results of external beam radiotherapy administered in six fractions per week and high-dose-rate (HDR) brachytherapy for the treatment of cervical cancer. METHODS AND MATERIALS: From July 2000 to July 2003, 43 patients were enrolled in this study. The patients received 45 Gy from a 10-MV photon beam using four-field box or anterior-posterior beams. Parametrial regions and the pelvic side walls were boosted with up to 50.4 Gy using a midline block. The daily fraction dose was 1.8 Gy administered in six-weekly fractions, from Monday to Saturday. HDR brachytherapy was also delivered at doses of 24 Gy to point A in six fractions twice a week. The median follow-up time was 37 months (range, 9-60 months). RESULTS: The median overall treatment time was 51 days for all patients (range, 44-62 days). Thirty-four patients (79.1%) achieved complete remission and 8 (18.6%) achieved partial remission after radiotherapy. Locoregional recurrence occurred in 5 patients (11.6%), and a distant metastasis was encountered in 6 patients (13.9%). The 3-year overall survival, locoregional, and distant metastasis-free survival rates were 74.7%, 87.8%, and 84.7%, respectively. Grade 2 and 3 late rectal complications were encountered in 3 (6.5%) and 1 (2.2%), respectively. There were no Grade 3 late bladder complications. CONCLUSIONS: Six fractions per week of external beam radiotherapy and HDR brachytherapy is an effective treatment for patients with a carcinoma of the uterine cervix and can be used as a possible alternative to concomitant chemoradiotherapy in elderly patients or in patients with co-morbidity.

Radiation therapy for abdominal lymph node metastasis from hepatocellular carcinoma.

BACKGROUND: We report the results of radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma (HCC). METHODS: From 1998 to 2004, 45 cases were treated with radiotherapy (RT), with a dose between 30 and 55 Gy. The radiation response, overall survival, prognostic factors, and complications were evaluated. RESULTS: Thirty-nine cases were able to be evaluated for response: 10 cases showed complete response; 21 cases showed a partial response; and 8 cases showed stable disease. The overall response rate was 79.5%. The response rate was 87.5% for patients receiving >or=40 Gy(10) (biologically effective dose, alpha/beta = 10) and 42.9% for patients receiving <40 Gy(10) (P = 0.02). The median survival time was 10 months for responders and 6 months for nonresponders (P = 0.01). The absence of other concurrent distant metastasis and controllable primary HCC were significant prognostic factors. RT induced gastric or duodenal ulcer development in nine patients. All of these patients had received more than 50 Gy(10), and these complications were not detected among patients receiving <50 Gy(10) (0% vs 37.5%, P < 0.01). CONCLUSIONS: RT was an effective treatment modality, and the absence of concurrent distant metastasis and controllable primary tumor were significant prognostic factors. However, considering the high rate of RT-induced morbidity, 40 Gy(10) to 50 Gy(10) might be the optimal RT dose.

Local radiotherapy for patients with unresectable hepatocellular carcinoma.

PURPOSE: To evaluate the response to local radiotherapy (RT) for unresectable hepatocellular carcinoma (HCC) and to analyze the dose-response relationship and the treatment-related morbidities. METHODS AND MATERIALS: Between 1998 and 2002, 59 patients who were treated with localized RT were evaluated. RT was delivered with a curative intent, and the radiation dose was 30-55 Gy (biologic effective dose of 39.0-70.2 Gy(10) using the alpha/beta ratio of 10 Gy) with 2-3 Gy as a daily dose. The tumor response was evaluated by the change in maximum tumor size on serial CT scans, and the morbidity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. RESULTS: An objective tumor response was achieved in 39 of 59 patients (66.1%) with complete response (CR) in 5 patients and partial response (PR) in 34 patients. More than 50 Gy(10) had a significant response; CR or PR was 72.8% with >50 Gy(10) and 46.7% with < or =50 Gy(10) (p = 0.0299). The 2-year overall survival rate after RT was 27.4% (median survival time: 10 months), and this was affected by the tumor response (p = 0.0640); the 2-year overall survival rate after RT was 50.0% for CR and 21.8% for PR. There was no Grade 3 or 4 acute toxicity, and 3 patients (5.1%) developed gastric or duodenal ulcer. CONCLUSIONS: Radiotherapy for unresectable HCC resulted in 66.1% of tumor response with acceptable toxicity, and the radiation dose seems to be a significant prognostic factor in RT response for HCC.

Clinical outcomes after sentinel lymph node biopsy in clinically node-negative breast cancer patients.

PURPOSE: To evaluate non-sentinel lymph node (LN) status after sentinel lymph node biopsy (SNB) in patients with breast cancer and to identify the predictive factors for disease failure. MATERIALS AND METHODS: From January 2006 to December 2007, axillary lymph node (ALN) dissection after SNB was performed for patients with primary invasive breast cancer who had no clinical evidence of LN metastasis. A total of 320 patients were treated with breast-conserving surgery and radiotherapy. RESULTS: The median age of patients was 48 years, and the median follow-up time was 72.8 months. Close resection margin (RM) was observed in 13 patients. The median number of dissected SNB was two, and that of total retrieved ALNs was 11. Sentinel node accuracy was 94.7%, and the overall false negative rate (FNR) was 5.3%. Eleven patients experienced treatment failure. Local recurrence, regional LN recurrence, and distant metastasis were identified in 0.9%, 1.9%, and 2.8% of these patients, respectively. Sentinel LN status were not associated with locoregional recurrence (p > 0.05). Close RM was the only significant factor for disease-free survival (DFS) in univariate and multivariate analysis. The 5-year overall survival, DFS, and locoregional DFS were 100%, 96.8%, and 98.1%, respectively. CONCLUSION: In this study, SNB was performed with high accuracy and low FNR and high locoregional control was achieved.

Definitive radiation therapy for early glottic cancer: experience of two fractionation schedules.

OBJECTIVES: The authors would report the results of definitive radiation therapy (RT) for early glottic cancer by two different radiation dose schedules. METHODS: From February of 1995 till June of 2008, 157 patients with T1-2N0 glottic cancer were treated with curative RT at Samsung Medical Center. All patients had squamous cell carcinoma, and there were 89 patients (56.7%) with T1a, 36 (22.9%) with T1b, and 32 (20.4%) with T2. Two different radiation dose schedules were used: 70 Gy in 35 fractions to 64 patients (40.8%, group A); and 67.5 Gy in 30 fractions to 93 patients (59.2%, group B). The median treatment durations were 50 days (range, 44 to 59 days) and 44 days (range, 40 to 67 days) in the groups A and B, respectively. RESULTS: The median follow-up durations were 85 and 45 months for the groups A and B. No severe late complication of RTOG grade 3 or higher was observed, and there was no difference in acute or chronic complication between the groups. Twenty-four patients experienced treatment failure: local recurrence only in 19 patients; regional recurrence only in one; combined local and regional recurrence in four; and systemic metastasis in none. The overall 5-year disease-free survival and disease-specific survival rates were 84.7% and 94.8%. The disease-free survival rate in the group B was better (78.3% vs. 90.8%, P=0.031). This difference was significant only in T1 stage (83.4% vs. 94.6%, P=0.025), but not in T2 (62.7% vs. 60.6%, P=0.965). Univariate analysis showed that the tumor extent, cord mobility, T-stage, and the dose schedule had significant influence on the disease-free survival, and multivariate analysis showed that only the tumor extent and the dose schedule were associated with the disease-free survival. CONCLUSION: Superior disease-free survival could be achieved by 2.25 Gy per fraction without increased toxicity over shorter RT duration, when compared with 2.0 Gy per fraction.

A matched-case comparison to explore the role of consolidation chemotherapy after concurrent chemoradiation in cervical cancer.

PURPOSE: The aim of this study was to compare the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) and CCRT alone in patients with locally advanced cervical carcinoma. METHODS AND MATERIALS: Using medical records from January 2001 to December 2007, 39 patients treated with consolidation chemotherapy after CCRT (Group 1) were matched to 39 patients treated with CCRT alone (Group 2). Consolidation chemotherapy consisted of three additional cycles of chemotherapy with cisplatin 60 mg/m2 (Day 1) and 5-fluorouracil 1,000 mg/m2 per day (Days 1-5) given every 3 weeks. The primary endpoint was overall survival. RESULTS: During a median follow-up period of 35 months (range, 8-96 months), 10 (25.6%) and 16 (41.0%) patients showed disease progression in Groups 1 and 2, respectively. Distant recurrence with or without locoregional/lymphogenous recurrence occurred more frequently in Group 2 than in Group 1 (23.1% vs. 7.7%, p=0.06). By contrast, there was no difference in locoregional or lymphogenous recurrence between the two groups. The rate of overall survival was higher in Group 1 than in Group 2 (92.7% vs. 69.9%, p=0.042), whereas the difference in progression-free survival between the groups was not statistically significant (70.1% vs. 55.1%, p=0.079). Although the difference was not statistically significant, neutropenia was more common in Group 1 than in Group 2 (10.9% vs. 4.7%, p=0.07). CONCLUSIONS: Consolidation chemotherapy after CCRT may improve survival and reduce distant recurrence without additional toxicity compared to CCRT alone in patients with locally advanced cervical carcinoma.

Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy.

BACKGROUND: The purpose of this study was to analyze the prognostic factors affecting local control and survival rates for patients with early breast cancer who received breast conserving treatment (BCT) and to find out the optimal treatment according to their risk factors. METHODS: From October 1994 to December 2001, 605 patients with 611 stage I and II breast cancers received BCT, and the results were analyzed retrospectively. BCT consists of breast conserving surgery and whole breast irradiation. All the patients underwent lumpectomy or quadrantectomy. Axillary lymph node dissection or sentinel lymph node biopsy was performed in 608 cases (99.5%). The radiation dose to the whole breast was 50.4 Gy over 5 weeks with a 1.8 Gy daily fraction and with boost doses of 9-14.4 Gy administered to the tumor bed. Adjuvant chemotherapy was performed in most of the patients with axillary lymph node metastasis or tumors larger than 1 cm. The median follow-up period was 47 months. RESULTS: Local relapse, regional relapse and distant metastasis occurred in 15 (2.5%), 16 (2.6%) and 43 patients (7.1%), respectively. The 5-year overall survival, local-relapse-free survival, distant-metastasis-free survival and disease-free survival rates were 95.3%, 97.2%, 91.3% and 88.5%, respectively. On multivariate analysis, age (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.01) affected the local-relapse-free survival. The factors associated with disease-free survival were the T stage (P = 0.05), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.001). Overall survival was associated with the T stage (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and c-erb B2 overexpression (P = 0.05). Patients with more than two factors among (i) age 1 cm, (ii) positive lymph node metastasis and (iii) high nuclear grade showed an inferior 5-year disease-free survival rate compared with others (P = 0.0005). CONCLUSIONS: The most important prognostic factor affecting local control, disease-free survival and overall survival was axillary lymph node metastasis. The nuclear grade influenced local control and disease relapse. Patients with multiple unfavorable risk factors such as positive axillary lymph nodes, high nuclear grade, young age and large tumor showed poorer local control and disease-free survival than patients without any risk factors, and so more aggressive treatment is required for these patients.

High Dose Radiation Therapy Concurrent with Chemotherapy in Locally Advanced Nasopharynx Cancer.

PURPOSE: Here, our results from a prospective treatment protocol of concurrent radiochemotherapy (CRCT), which was conducted for locally advanced nasopharynx cancers, between April 1994 and May 2001, are reported. MATERIALS AND METHODS: A total of 52 consecutive eligible patients were accumulated for this protocol. The median radiation doses to the primary site, involved nodes and uninvolved neck were 72, 61.2 and 45 Gy, using a serial shrinking field technique. The boost techniques were 3-dimensional conformal radiation therapy in 45, intracavitary brachytherapy in 3 and 2-dimensional radiation therapy, with multiple small fields, in 2 patients. Two chemotherapy regimens were used: the first regimen, used in 8 patients during the earlier part of the study duration, consisted of 2 cycles of cisplatin plus 5- fluorouracil every 4 weeks, with concurrent radiation therapy, and 4 cycles with the same agents every 4 weeks, adjuvantly; the second regimen, used in 44 patients during the later part, consisted of 3 cycles of cisplatin every 3 weeks, with concurrent radiation therapy and 3 cycles of adjuvant cisplatin plus 5-fluorouracil every 3 weeks. RESULTS: The median follow-up period of the survivors was 32 months. The male to female ratio was 36/16, with a median age of 48 years. The stages, according to the new AJCC staging system (1997), were IIb in 6, III in 23, IVa in 14 and IVb in 9 patients. Fifty and 32 patients completed the planned radiation therapy and concurrent chemotherapy, respectively. Two patients died, 1 of septic shock during the CRCT and the other of malnutrition during the adjuvant chemotherapy. There were 12 failures in 11 patients: 7 locoregional recurrences, 1 within and 6 outside the radiation target volume, and 5 distant metastases. The locoregional control, disease-free survival and overall survival rates were 84.3, 78.8 and 92.8% at 3 years, respectively. CONCLUSION: High dose radiation therapy, coupled with concurrent chemotherapy, was judged a highly effective treatment for locally advanced nasopharynx cancers.