Intensity-modulated radiotherapy for nasopharyngeal carcinoma: the reduction of radiation-induced trismus.

The purpose of this study was to evaluate the degree of radiation-induced trismus after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). From 2003 to 2004, 17 non-metastatic NPC patients treated with parotid-sparing IMRT were enrolled. The maximal interincisal distance (MID) was measured to represent the maximum mouth opening. All 17 patients had both pre- and post-IMRT measurements taken, and the normalized MID (post-IMRT MID/pre-IMRT MID) was analysed to evaluate the percentage decrease in MID after IMRT. The median follow-up time was 20.5 months. One patient had nodal failure and was successfully salvaged with radiotherapy. All 17 patients were alive without cancer at the last follow-up. The average MID before IMRT was 46.2 mm (standard deviation (SD), 8.6 mm). The average MID at 12 months post-IMRT was 45.4 mm (SD, 8.9 mm). The averages of normalized MID were 94% (SD, 3.9%) at 5 months post-IMRT and 98.1% (SD, 4.2%) at 12 months post-IMRT. Based on the satisfactory preservation of normalized MID (average of 98.1% at 12 months post-IMRT), we demonstrate that IMRT reduces radiation-induced trismus in NPC patients. The recovery of normalized MID exists in the period from 5-12 months post-IMRT.

Lymphoepithelioma-like carcinoma of salivary glands: treatment results and failure patterns.

The purpose of this study was to evaluate the treatment results and failure patterns of lymphoepithelioma-like carcinoma (LELC) of salivary glands. From June 1987 to May 2001, nine patients with LELC of salivary glands were treated at our hospital. One patient was excluded due to the loss of clinical follow-up after surgery. For the remaining eight patients, the primary tumour sites were parotid glands (4 patients), submandibular glands (3), and the minor salivary glands in right cheek (1), respectively. Seven patients underwent surgical treatment and post-operative radiotherapy, while the other one patient was treated with surgery only. The total radiation dose to the salivary tumour bed ranged from 39.6 Gy to 67.6 Gy (mean dose: 58.3 Gy and median dose: 59 Gy). The treatment results and failure patterns were analysed. The survival time ranged from 21.4 months to 145.2 months (mean: 69.1 months, median: 54.5 months). At the end of follow-up, six patients were still alive and two died. One patient died of distant metastases 21.5 months after the surgical treatment of LELC. The other case died of intercurrent disease (pontine haemorrhage) 53 months after surgery. No patient had local or regional failure after the treatments. Distant failure was noted in two patients. The patients with LELC of salivary glands were shown to have favourable prognoses. No local or regional failure was noted. However, distant failure developed in two patients. The risk of distant metastasis should be carefully monitored, especially for those patients with more advanced neck node involvement.

Treatment outcomes and prognostic factors in patients with supratentorial low-grade gliomas.

Low-grade gliomas account for 10-15% of all adult primary intracranial tumours. Currently, there is no consensus on the treatment strategy for low-grade gliomas. This study was designed to evaluate the treatment outcomes, prognostic factors and radiation-related late complications, as well as to assess whether or not post-operative radiotherapy has benefit on local control and overall survival in this population. We retrospectively reviewed 93 consecutive adult patients with supratentorial low-grade gliomas diagnosed at our institution from July 1985 to December 1997. All patients underwent surgical intervention and 60 of them received post-operative radiotherapy. With a median follow-up of 110 months for surviving patients, the 5-year overall and progression-free survival rates were 57% and 47%, respectively. 46 patients experienced local progression of disease during the follow-up period. In multivariate analysis, age at diagnosis, extent of surgery and post-operative Karnofsky performance status showed independent prognostic significance for progression-free and overall survival rates. Post-operative radiotherapy had independent prognostic value for progression-free survival. This analysis has changed our practice and we suggest that aggressive surgical resection and post-operative radiotherapy might be considered for patients with low-grade gliomas. Further efforts should be made to optimize radiotherapy techniques and to integrate new therapeutic modalities.

Attenuation of radiation dose by the skull base bone in patients with nasopharyngeal carcinoma: clinical importance.

PURPOSE: To measure the degree of attenuation of radiation dose by the skull base bone in patients with nasopharyngeal carcinoma (NPC) and to study its clinical importance. MATERIALS AND METHODS: Isodose distribution in 11 patients with NPC who received bilaterally opposed large-field irradiation (1.8 Gy per fraction) was studied with a three-dimensional treatment planning system with tissue inhomogeneity correction. Also studied were the sites of local tumor recurrence in 37 patients with NPC and skull base destruction (>/=0.5 cm) or intracranial invasion treated with radiation therapy from January 1989 to December 1992. Regression analyses were performed. RESULTS: In the dosimetric study, the low-dose areas (<1.65 Gy) were located at the level of the skull base in all 11 patients. A significantly positive correlation between the maximum width of the skull base bone and the low-dose volume (<1.65 Gy) was demonstrated (P =.003, linear regression). In the clinical study, local tumor recurrence was noted in 18 patients (49%). The sites of local recurrence included skull base in 16 patients (43%) and nasopharynx in six patients (16%). Wider skull base bone was a significant predictor of skull base recurrence after radiation therapy (P =.03, logistic regression). CONCLUSION: Herein demonstrated is the inadequacy of the radiation dose over the skull base due to attenuation by the skull base bone. The relationship between width of skull base bone and skull base tumor recurrence also is established.

High external parametrial dose can increase the probability of radiation proctitis in patients with uterine cervix cancer.

OBJECTIVE: The aim of this study was to evaluate the relationship between external parametrial dose and radiation proctitis after external irradiation and high-dose-rate intracavitary (HDR-IC) brachytherapy among patients with cervical cancer. METHODS: From May 1993 through December 1996, 191 patients with stage IB-IVA cervical cancer were managed by curative-intent radiotherapy. External irradiation to the whole pelvis (44-45 Gy/ 22-25 fractions) was delivered to all patients initially. One hundred twenty-seven patients received additional bilateral parametrial and sidewall boost (5.4-14.4 Gy/ 3-8 fractions) with 4-cm midline shielding. HDR-IC brachytherapy, 19.2-24 Gy/ 5 fractions to Point A, was given after external irradiation. Patients receiving an external dose of 44-45, 50-54, and >54 Gy were categorized as no parametrial boost (NPMB), low parametrial boost (LPMB), and high parametrial boost (HPMB) group, respectively. The actuarial proctitis rate was compared among the three groups. RESULTS: Three-year overall and Grade 2-4 proctitis rates were 30 and 15%, respectively. Overall proctitis rates were 12, 34, and 51% in the NPMB, LPMB, and HPMB groups (P < 0.0001), respectively. Grade 2-4 proctitis rates were 5, 17, and 27% in the NPMB, LPMB, and HPMB groups (P = 0.0022), respectively. In multivariate analysis of overall and Grade 2-4 radiation proctitis, external parametrial dose was the only independent prognostic factor (P = 0.0002 and 0.0030, respectively). CONCLUSION: Regardless of central shielding after 44-45 Gy whole pelvis irradiation, more patients with high external parametrial dose developed radiation proctitis. Incomplete midline shielding of the upper rectum may be the cause. Diminishing the external beam doses further may decrease rectal complications.

Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors.

BACKGROUND AND PURPOSE: To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer. MATERIALS AND METHODS: From July 1987 through July 1994, 109 women with stage II and III breast cancer receiving modified radical mastectomies were managed by postoperative electron beam irradiation. Doses of 46 to 50.4 Gy were delivered to the chest wall covered with bolus, internal mammary nodes, supraclavicular nodes and axillary lymph nodes via 12 or 15 MeV single portal electron beam. Seventeen patients received additional 10-16 Gy surgical scar boost via 9 MeV electron beam. Comparison of pre-treatment and post-treatment chest X-ray films were used to monitor the development of pulmonary fibrosis. RESULTS: Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P<0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P<0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis. CONCLUSIONS: In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis.

Concomitant boost radiation therapy for inoperable non-small-cell lung cancer: preliminary report of a prospective randomized study.

PURPOSE: The radiation therapy results for patients with inoperable non-small-cell lung cancer (NSCLC) have been disappointing. Tumor dose escalation using concomitant boost technique (CBT) has been shown to improve local control in a few prospective studies. This trial was carried out to prospectively assess the radiation response and acute toxicity of CBT in comparison to the conventional treatment technique (CTT). METHODS AND MATERIALS: Ninety-seven consecutive eligible patients were entered in this prospective clinical trial between November 1994 and February 1998. Patients were randomized to receive either CBT (43 patients) or CTT (54 patients) radiation therapy. These patients either refused chemotherapy or were judged as unsuitable for chemotherapy. Patients in the CBT group received 46.8 Gy in 26 fractions using large fields that encompassed the gross and occult disease. A concomitant boost of 18.2 Gy (0.7 Gy per fraction) was delivered to the gross disease using small fields with 1.5-cm margins. The small fields were treated concurrently with the large fields and the total dose to the tumor area was 65 Gy in 26 fractions. Patients in the CTT group received 70.8 Gy in 38 fractions. The acute toxicity between each group was compared. The response rate was analyzed and compared by treatment group, gender, age, stage, histology, initial Karnofsky performance score (KPS), severity of acute toxicity, and maximum body weight loss (MBWL) during treatment course. RESULTS: The demographic parameters such as sex, age, and stage were evenly distributed in each treatment group. The majority of these patients had Stage IIIA and IIIB disease. Overall median treatment times were 39 days for the CBT group of patients and 62 days for the CTT group. No treatment-related mortality was found. There were 2 patients in the CTT group with acute RTOG Grade 3 lung toxicity, and no Grade 3 lung or esophageal toxicity was observed in CBT group. The response rates, assessed by radiographic images, were 69.8% and 48.1% for the CBT and CTT patients, respectively. Univariate and multivariate analysis revealed that patients in the CBT group, patients with better KPS, and patients with more severe acute toxicity had a higher response rate. CONCLUSION: This study demonstrates that concomitant boost radiation therapy is tolerable, and produces a superior response rate than conventional radiation therapy for patients with inoperable NSCLC. The length of treatment was reduced from 38 to 26 treatment days, almost a 30% reduction.

Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial.

PURPOSE: To evaluate the influence of oral glutamine on radiation-induced oral mucositis in the radiotherapy of head and neck cancer. METHODS AND MATERIALS: From July 1997 through June 1998, 17 patients with head and neck cancer receiving primary or adjuvant irradiation were randomized to either glutamine suspension (16 g in 240 ml normal saline) (n = 8) or placebo (normal saline) (n = 9) arm. Patients were instructed to swish the test solutions (30 ml) four times per day. All patients received half-mouth irradiation at least. Patients were treated 1.8 Gy per fraction daily, 5 days a week. We evaluated the grading of oral mucositis daily fraction at each day of treatment until 45 Gy/25 fractions. World Health Organization (WHO) step analgesic medication and body weight change were compared between the two arms. RESULTS: The duration of objective oral mucositis > or = Grade 1 (p = 0.0097), Grade 2 (p = 0.0232), and Grade 3 (p = 0.0168) was shorter in the glutamine arm. Mean maximum grade of objective oral mucositis was less severe in the glutamine arm (1.6 vs. 2.6) (p = 0.0058). Glutamine did not reduce the duration and severity of subjective oral mucositis except for duration > or = Grade 3 (p = 0.0386). In the analysis of mean maximum WHO step of analgesic medication, there was no statistical difference (p = 0.5374) between the two arms. Mean body weight change was also not significantly different (p = 0.8070). CONCLUSIONS: Oral glutamine may significantly reduce the duration and severity of objective oral mucositis during radiotherapy. It may shorten the duration of > or = Grade 3 subjective mucositis.

Radiation therapy in primary central nervous system lymphoma.

BACKGROUND: Treatment of primary central nervous system lymphoma (PCNSL) in Chinese individuals has rarely been reported. Therefore, this article presents our experience in managing PCNSL with radiotherapy. METHODS: A thorough review was made of the medical records of 13 patients diagnosed with PCNSL at Kaohsiung Chang Gung Memorial Hospital from 1988 through 1997. The clinical characteristics, treatment modalities, and results were analyzed as well. RESULTS: Thirteen patients diagnosed with PCNSL were identified, of which 10 cases originated in the brain whereas three were of spinal origin. Seven of the patients were man and six were women, with a mean age of 54.9 +/- 13.1 years (range 29 to 74 years). Diffuse large cell lymphoma (11 cases) was the most common histology. Limb weakness (11 cases) and headache (7 cases) were the most common complaints at presentation. Nine patients received radiation therapy alone and four patients received radiation therapy plus chemotherapy after surgical resection or biopsy. Follow-up computed tomography (CT) scans 3 to 4 months after the completion of radiotherapy revealed that nine patients (69%) had a complete response and four (31%) had a partial response. Local recurrence occurred in five patients (56%) treated with radiation therapy alone and in one patient (25%) treated with combined modalities. The overall actuarial survival rate was 54% at 2 years and 27% at 5 years. CONCLUSION: Results in this study indicate that the initial response to radiotherapy is satisfactory. However, a local relapse frequently occurs. Future considerations should focus on new modes of treatment, such as three-dimensional conformal radiation therapy for dose escalation or a combination of chemotherapy and radiotherapy.

Management of choroidal melanomas with linear accelerator-based stereotactic radiosurgery.

PURPOSE: To discuss the technical aspect, dose prescription, clinical results, and biological responsiveness of linear accelerator-based stereotactic radiosurgery for choroidal melanoma. METHODS: From March 1995 to December 1995, three choroidal melanoma patients were treated with Linac-based radiosurgery in our department. Two patients underwent one dose of radiosurgery with 18 and 20 Gy in single fraction, respectively. The third patient received two doses of radiosurgery with a total dose of 35 Gy. RESULTS: Follow-up time ranged from 19 to 25 months (median: 24 months). One patient had near-total regression, while the other two patients had partial response on the last MR images. Visual acuity was deteriorated in all patients. One patient developed a radiation-induced cataract in the treated eye. CONCLUSION: Linac-based radiosurgery is technically feasible for management of choroidal melanoma. Although visual acuity was not improved in these patients, they appreciated the preserving of the eyeball without affecting their general appearance.

The prognostic factors of lung cancer patients with brain metastases treated with radiotherapy.

PURPOSE: To analyze the prognostic factors of lung cancer with brain metastases (BM) and evaluate the role of cranial irradiation on survival. METHODS AND MATERIALS: From 1987 to 1994, 159 lung cancer patients with CT scan documented BM were reviewed. All of them underwent cranial irradiation (median radiation dose: 30 Gy). Chemotherapy and surgery of BM were performed in 21 and 10 cases, respectively. RESULTS: Overall median survival was 3.5 months and one year survival rate was 10.69%. Univariate analysis showed that the significant factors were performance status, age, total radiation dose to brain, BM as the first metastasis, neurosurgery, symptoms of urine/stool incontinence, and synchronous BM. Multivariate analysis indicated that (1) performance status (p = 0.0002), (2) total radiation dose (p = 0.0032), (3) BM as the first metastasis (p = 0.0449), (4) neurosurgery (p = 0.0233), (5) symptoms of urine/stool incontinence (p = 0.0002), and (6) the presence of a midline shift on cranial CT scans (p = 0.0063) were significant prognostic factors. CONCLUSION: The prognosis of BM in lung cancer patients is extremely poor. Radiotherapy appears as an effective means of palliation with 75% overall symptomatic response rate. Higher radiation dose (> or = 30 Gy) and neurosurgery are associated with longer survival. Good performance status, BM as the first metastasis, absence of sphincter dysfunction, and midline shift on CT scans are favorable prognostic predictors. The role of midline shift is very interesting and needs to be explored further.

The correlation of acute toxicity and late rectal injury in radiotherapy for cervical carcinoma: evidence suggestive of consequential late effect (CQLE).

PURPOSE: To correlate the acute toxicity during pelvic irradiation and the development of late rectal injury following radiation therapy for cervical carcinoma. METHODS AND MATERIALS: Two hundred and twenty patients treated with curative-intent radiation therapy between November 1987 and January 1992 were analyzed. Patients were treated initially with external beam irradiation, 40-44 Gy/20-22 fractions to whole pelvis, followed by high dose rate intracavitary brachytherapy, 7.2 Gy to point A for 3 fractions. Severity of diarrhea during radiation therapy was scored according to six criteria: fecal characteristics, frequency, onset, prescription of antidiarrheal agents, body weight loss during irradiation, and extramedical care needed. Patients were categorized as group ND (no obvious diarrhea), group MD (moderate diarrhea), and group SD (severe diarrhea) for sum score 0-1, 2-5, and > or = 6, respectively. The rate of radiation proctitis was expressed, analyzed, and compared with actuarial proctitis-free rate and prevalence. RESULTS: 1) According to the score, 76 (35%), 89 (40%), and 55 (25%) patients were categorized as group ND, group MD, and group SD, respectively. Distribution of patients and treatment characteristics among the three groups appeared similar. Patients treated with a larger field size, > or = 16.5 cm2, tended to have increased severity of diarrhea. 2) Overall, 103 patients (47%, 103 of 220) developed radiation proctitis. Twenty-one patients were in group ND (28%, 21 of 76), 43 in group MD (48%, 43 of 89), and 39 in group SD (71%, 39 of 55). 3) The five-year actuarial proctitis-free rate was 72, 52, and 29% for group ND, MD, and SD, respectively (p < 0.005). 4) Taking time evolution and recoverability into account, the effect of diarrhea on the prevalence of radiation proctitis remained statistically significant at the first through the fourth year after irradiation. 5) Severity of radiation proctitis and severity of diarrhea were not correlated (Spearman's rank correlation coefficient r(s) = 0.229, p = 0.098). 6) Cox's multivariate analysis revealed that severity of diarrhea was the only factor that significantly correlated with the development of radiation proctitis. CONCLUSION: Patients with increased acute toxicity and diarrhea during radiation therapy of cervical carcinoma significantly increased the risk of late rectal injury. This result suggested that early excessive damage of acute-responding component of rectal wall may play an important role in the initiation of late rectal injury. Radiation proctitis can be accounted, in part, as a consequential late effect.