In-field Local Recurrence Research Articles

High-dose, Hypo-fractionated X-ray Radiotherapy for Hepatocellular Carcinoma: Tumor Responses and Toxicities

To evaluate the effect of high-dose photon radiation therapy (RT) in patients with hepatocellular carcinoma (HCC) and to analyze dose-response relationship and the factors associated with radiation-induced liver disease (RILD). From 1998 to 2008, forty patients with non-metastatic HCC undergoing curative-attempt radiotherapy by three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT) were reviewed. The median fraction size was 3 Gy/fraction and radiation dose was 40-66 Gy in 14-23 fractions (biologic effect dose of 52.0-85.8 Gy10 using the α/β ratio of 10Gy; median, 74.1Gy10). The fraction size was reduced if bowel was included in the planning tumor volume (PTV) and prescribed dose was determined by the constraints given to the normal liver. Among the 40 patients, regression of tumors was observed in 28 patients (70%), with complete response (CR) in 11 patients (27.5%) and partial response (PR) in 17 patients (42.5%), and stable disease (SD) and progressive disease (PD) was found in 5 patients (12.5%), and r 7 patients (17.5%), respectively. Outcomes of overall survival (OS), in-field local recurrence free survival (IFLRFS) and distant metastasis free survival (DMFS) were significantly better in non-progression group (33 patients with CR, PR or SD) than in progression group (7 patients with PD) by univariate analysis (2-year OS: 45.5% vs. 14.3%, p = 0.022; 2-year IFLRFS: 79.1% vs. 19.0%, p<0.001; 2-year DMFS: 83.0% vs. 33.3%, p<0.001, respectively) and multivariate analysis (p = 0.011, <0.001, 0.001, respectively). There was a positive relationship between radiation dose and tumor response; better tumor response and IFLRFS was found from biologic effect dose 55Gy10 to 74Gy10 (2-year IFLRFS <55Gy10 vs. ≥55Gy10, 17.9% vs. 80.3%, p<0.001; <74Gy10 vs. ≥74Gy10, 48.9% vs. 81.9%, p = 0.012). Eight of 40 patients (20%) developed non-classic RILD (measured by a worsening of Child-Pugh score by 2 or more). Patients with non-classic RILD was associated with Cancer of the Liver Italian Program (CLIP) score 2 or above (p = 0.003). Tumor response of HCC after high-dose irradiation is significantly associated with OS, IFLRFS, and DMFS, and the radiation dose is a significant factor for IFLRFS and RT tumor response. High-dose, hypo-fractionated photon RT is a feasible and effective treatment for HCC patients who meet the criteria for curative attempt and have good liver function (CLIP<2).

Treatment Outcomes of Radiotherapy for Patients With Stage I Esophageal Cancer

To evaluate the effectiveness of radiotherapy for patients with stage I esophageal cancer. From 1995 to 2005, 34 patients with superficial thoracic esophageal squamous cell carcinoma without lymph node metastasis were treated with radiotherapy at our institute. Patient characteristics were as follows: median age, 68 years; range, 47 to 84 years; male:female, 33:1; performance status, 0/1/2/3 = 23/9/1/1; T1a/T1b = 4/30. Median fraction and total doses of external irradiation given were 2.0 Gy and 60 Gy, respectively. Twenty-three patients had local irradiation to the primary lesion only; the remaining 11 patients received regional field irradiation, including one or 2 regional lymph node areas. Only one patient received adjuvant intracavitary radiotherapy after radiotherapy. Thirty of the patients received concurrent chemotherapy, most of the regimens of which included cisplatin and 5-fluorouracil. Adjuvant chemotherapy was performed in 5 patients. Fifteen patients (44%) had coexisting malignancies. The median follow-up was 38 months (range, 8-107 months). The 5-year overall, cause-specific, and local-progression-free survival rates were 50.4%, 91.2%, and 81.1%, respectively. Of the 34 patients, 6 had in-field local recurrence, and one had recurrence in the esophagus outside of the irradiated field. Two patients experienced regional lymph node metastasis outside of the irradiated field, and one had distant metastasis. Two patients received salvage surgery, and 4 patients received salvage intracavitary radiotherapy after local recurrence. A late toxicity greater than grade 2 was not observed in any patient. Radiotherapy is an effective treatment modality for patients with stage I esophageal cancer.

Analysis of Local Control in Patients with Non-Hodgkin’s Lymphoma According to the WHO Classification

To analyze the influence of radiotherapy doses, chemotherapy doses, and clinical parameters on in-field disease control to assess the optimal radiation doses for treatment of non-Hodgkin's lymphoma according to the newly proposed WHO classification. Subjects consisted of 35 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type, 75 diffuse large B-cell lymphomas (DLBCL), 14 follicular lymphomas, 17 extranodal natural killer (NK)/T-cell lymphomas, nasal type, eight unclassified peripheral T-cell lymphomas, four anaplastic large-cell lymphomas, T/null cell type, and five others. 59 patients received radiotherapy alone. 98 patients received CHOP, modified CHOP, or more intensive chemotherapy, and six patients were treated with other combination. No patients with MALT lymphoma had in-field local recurrence. There were no recurrences in DLBCL patients who received chemotherapy in which the doses of adriamycin were > 200 mg/m(2), nor in DLBCL patients who were treated with > 45 Gy. Only nine of 15 patients with T-cell lymphoma treated with < or = 50 Gy and three of five patients treated with > 50 Gy had local control. The dose of adriamycin had no influence on local control of T-cell lymphoma. T/NK-cell lymphomas were more radioresistant than B-cell lymphomas. The prognosis for peripheral T/NK-cell lymphomas is poor even when treated by irradiation combined with chemotherapy.

Clinical Results of Radiation Therapy for Stage I Esophageal Cancer

From 1992 through 2001, 29 patients with stage I esophageal cancer were treated with radiation therapy. All patients had squamous cell carcinoma. Seventeen patients were treated with radiotherapy alone, and 12 were treated with a combination of chemotherapy and radiotherapy. Most of the chemotherapy regimens included cisplatin and/or 5-fluorouracil (5-FU). Twelve patients were treated with intracavitary irradiation (low-dose rate: 6, high-dose rate: 6) after external radiotherapy. Median fraction and total doses of external radiotherapy given were 2.0 Gy and 60.6 Gy, respectively. Median doses of intracavitary irradiation were 18 Gy/6 fractions in low-dose-rate brachytherapy and 13.5 Gy/4.5 fractions in high-dose-rate brachytherapy. The 5-year overall survival rate was 62%. The 5-year local control rate was 44%. Of the 29 patients, 9 had in-field recurrence in the esophagus and 1 had recurrence in the esophagus outside of the irradiated field. Of 9 patients with in-field local recurrence, 1 also developed mediastinal lymph node metastases and 1 had distant metastasis. Radiation therapy is an effective treatment modality for stage I esophageal cancer.

Local resection and brachytherapy confined to the lumpectomy site for early breast cancer: a pilot study.

The commonest site of local breast recurrence after breast conservation surgery is the primary tumor bed. We have tested the feasibility of outpatient high dose rate brachytherapy to the primary tumor bed as the only radiation. Our technique relies on the placement of surgical clips to mark the tumor bed. Between March 1992 and January 1996, 39 patients with clinical T1 T2 breast cancer were enrolled in this pilot study. The first 13 patients had intraoperative implantation of the breast. The remaining 26 patients had outpatient postoperative implantation under general anesthesia (2 patients) or local anaesthesia (24 patients). High dose rate brachytherapy was given twice daily at least 6 hours apart for a total dose of 37.2 Gy in 10 fractions over 5-7 days. Three patients had mild clinical cellulitis responding to oral antibiotics. One patient had a small sinus in the lumpectomy scar requiring local excision to heal. Four patients developed fat necrosis at the lumpectomy site at 4 (1 patient), 13 (1 patient), and 18 months (2 patients) post radiotherapy. Patient rated satisfaction with treatment was high. At a median followup of 20 months, one infield local recurrence has been salvaged by wider resection and postoperative conventional external beam radiation. Except for fat necrosis, which may be associated with this technique, complications have been minimal. Outpatient implantation under local anesthesia is feasible. Longer followup is required to establish the local control rates.

Reduction of the radiation dose for intracranial germinoma: a prospective study

Intracranial germinoma has usually been treated with radiation doses of 50 Gy or more, but it is unclear whether such doses are actually necessary to cure this radiosensitive tumour. At our institution, the standard radiation dose for intracranial germinoma was 60 Gy in the 1960s, but the dose has prospectively been reduced stepwise to 40-45 Gy. In this paper, the treatment outcome was assessed in 84 patients (47 with histologically confirmed disease and 37 diagnosed clinically in the post-computerised tomography era) enrolled in both prospective and retrospective series. The 5 and 10 years survival rates for all 84 patients were 88% and 83% respectively, and the corresponding relapse-free survival rates were 88% and 85%. The 10-year relapse-free survival rate was 88% for 31 patients receiving 19-47 Gy (median 42 Gy) to the primary tumour, 92% for 28 patients receiving 48-52 Gy (median 50 Gy), and 83% for 25 patients receiving 54-62 Gy (median 60 Gy), and there was no significant difference among the three groups. In-field local recurrence only developed in one patient who received 40 Gy over a protracted period and one patient who received 60 Gy. A tumour size < 3 cm and treatment in the post-computerised tomography era were associated with a better prognosis according to univariate analysis, while age, sex, tumour site, treatment volume, the radiation dose to both the primary and the spinal cord and the extent of surgical resection did not influence the prognosis. In contrast, none of these factors had a significant influence in multivariate analysis. In conclusion, intracranial germinomas < or = 4 cm in size can usually be cured with 40-45 Gy of radiation, thus avoiding the major adverse effects of brain irradiation.