Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose-volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer.

OBJECTIVE: We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose-volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose-volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). METHODS: The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle(3) system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2-T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V(20 Gy) and V(30 Gy) of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. RESULTS: Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V(20) (Gy), and heart V(30) (Gy) in the DV-gEUD plan were lower than those in the DV plan (p<0.05). CONCLUSIONS: A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV.

Dual arc volumetric-modulated arc radiotherapy (VMAT) of nasopharyngeal carcinomas: a simultaneous integrated boost treatment plan comparison with intensity-modulated radiotherapies and single arc VMAT.

AIMS: To compare the performance of volumetric-modulated arc radiotherapy (VMAT) by dual arc with fixed beam intensity-modulated radiotherapies (IMRTs) and single arc VMAT on nasopharyngeal carcinomas (NPC). MATERIALS AND METHODS: Twenty NPC cases were re-planned using the planning system of the Pinnacle(3®)SmartArc (SA) module to compare the performance of the following four techniques: seven-field (7F) and 18-field (18F) fixed beam IMRT, and single (SA(1)) and dual arc VMAT (SA(2)). The plan was delivered on an Elekta Synergy™ Linac equipped with an 80-leaf 1cm multileaf collimator. Three dose levels of planning target volumes (PTVs) with 70/59.4/54.0Gy in 33 fractions were prescribed and delivered as a simultaneous integrated boost. The conformity index and homogeneity index of the PTVs, the comprehensive quality index (CQI), the normal tissue complication probability for the organs at risk (OARs), and the planning time, delivery efficiency and accuracy were analysed. RESULTS: A significantly inferior conformity index at the three dose levels of PTV and homogeneity index of PTV(70) were observed in SA(1) compared with the other techniques. Comparable conformity index and homogeneity index of the PTV were observed among 7F/18F IMRT and SA(2). Based on the CQI of the 11 OARs, the most efficient dose reduction was observed in 18F IMRT followed in order by SA(2), 7F IMRT and SA(1). The planning time was on average 13.2/24.9/40.1/42.8min for 7F/18F IMRT/SA(1)/SA(2), respectively. With regards to the delivery efficiency compared with 7F IMRT, a 51 and 41% reduction in delivery time was achieved by SA(1) and SA(2), respectively. All techniques presented a high quality assurance pass rate (>98%) of the Γ(3mm,3%) criterion. CONCLUSION: In NPC cases, SA(2) gave superior results in terms of PTV coverage and OAR sparing compared with SA(1) and approached the performance achieved by 18F IMRT, but without sacrificing the delivery efficiency.

Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity.

Matrix metalloproteinase (MMP)-2 plays critical roles in tumor development and in the metastasis of multiple cancers, including human oral cavity squamous cell carcinoma (OCSCC). One of the upstream regulators of MMP-2 is FOXM1, which is overexpressed in a microarray dataset of OCSCC. It is interesting that FLJ10540 exhibits similar gene expression profiles with MMP-2 and FOXM1, raising the possibility that these molecules might participate in MMP-2-elicited cancer progression and metastasis of OCSCC. To examine this connection, we first showed that FLJ10540 was significantly overexpressed in OCSCC. A strong FLJ10540 expression was significantly correlated with an advanced tumor node metastasis stage and the cumulative 5-year survival rate. Thus, an elevated FLJ10540 expression is an indicator of poor survival. Functionally, FLJ10540 had the abilities to stimulate cell migration and invasion in oral cancer cells through increased FOXM1 and MMP-2 expressions. Conversely, the depletion of the FLJ10540 expression by small interfering RNAs suppressed the FOXM1 and MMP-2 protein expressions. The suppression of either FLJ10540 or FOXM1 could cause significant inhibition on cell migratory and invasive ability in oral cancer cells. Finally, the immunohistochemical and western blotting analyses of human aggressive OCSCC specimens showed a significant positive correlation among FLJ10540, FOXM1 and MMP-2 expressions. These findings suggest that FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for OCSCC treatment.

Overexpression of beta2-microglobulin is associated with poor survival in patients with oral cavity squamous cell carcinoma and contributes to oral cancer cell migration and invasion.

beta2-Microglobulin (beta2M), a component of MHC class I molecules, is believed to be associated with tumour status in various cancers. In this study, we examined the expression of beta2M at different malignant stages of oral cavity squamous cell carcinoma (OCSCC). To determine the possible correlation between beta2M expression and various clinical characteristics, 256 samples from patients with OCSCC were evaluated by immunohistochemical staining. Strong beta2M expression was significantly correlated with a relatively advanced tumour stage (P<0.001), positive nodal status (P<0.001), and TNM stage (P<0.001). The cumulative 5-year survival rate was significantly correlated with a relatively advanced tumour stage (P<0.001), positive nodal status (P<0.001), TNM stage (P<0.001), and strong expression of beta2M (P<0.001). Thus, elevated beta2M expression is an indicator of poor survival (P<0.001). In addition, we extended our analysis of beta2M expression to the FaDu and SCC25 oral cancer cell lines. beta2-Microglobulin expression was positively correlated with cell migration and invasion in beta2M-overexpressing transfectants in Transwell chambers. The suppression of beta2M expression using small interfering RNA (siRNA) was sufficient to decrease cell migration and invasion in vitro. Taken together, our results suggest that beta2M expression in the tissues is associated with survival and may be involved in tumour progression and metastasis in OCSCC.

Radiation therapy to non-iatrogenic subcutaneous metastasis in hepatocellular carcinoma: results of a case series.

Non-iatrogenic subcutaneous metastasis of hepatocellular carcinoma (HCC) is rare. The aim of this study was to determine the characteristics of such non-iatrogenic subcutaneous metastases and to review the results of radiation therapy. Patients with HCC who were referred for radiation therapy to a subcutaneous mass from 1 January 1998 to 31 December 2005 were reviewed. Iatrogenic cases were excluded. The patients' characteristics, the properties of the lesion, radiation treatment, treatment response, and survival were studied. 24 subcutaneous metastatic lesions in 21 patients were studied. The patients' mean age was 58.2 years. The average latency period for the occurrence of the metastases was 291 days. The scalp was the most frequent metastatic site. At least a partial response was achieved in 20 of 24 lesions (83.3%), with radiation doses ranging from 8 to 64 Gy. No severe sequelae were recorded. The overall 6-month survival was 43.4%. ECOG (Eastern Cooperative Oncology Group) performance status and radiation dose were statistically significant factors for local treatment response. Performance status was also an independent factor for survival. Radiation therapy of subcutaneous metastases of HCC can achieve satisfactory results, especially in patients with a good performance status.

Implications of quantitative tumor and nodal regression rates for nasopharyngeal carcinomas after 45 Gy of radiotherapy.

PURPOSE: To quantitatively investigate the clinical implications of tumor regression rate (TRR-45) and nodal regression rate (NRR-45) of nasopharyngeal carcinomas (NPC) after receiving 45 Gy of radiotherapy (RT). The values, predictive values, and associated factors of TRR-45 and NRR-45 in NPC are analyzed. METHODS AND MATERIALS: One hundred one patients with newly diagnosed NPC and who were curatively treated by RT alone were included in the study. Tumor volume and nodal volume before treatment and after 45 Gy were obtained from computed tomographic (CT) scans performed at those times and calculated with the assistance of a computer-based imaging analyzing system. TRR-45 (NRR-45) was defined as the ratio of reduced tumor (nodal) volume after 45 Gy to the initial tumor (nodal) volume. TRR-45 (NRR-45) values were stratified into three groups of slow (below 50%), moderate (between 50% and 75%), and rapid (above 75%) change. After conventional RT with 45 Gy, conformal RT for primary tumors was boosted to 70.2-72 Gy for T1-2 tumors, and 75.6-81 Gy for T3-T4 tumors. RT for residual neck masses was boosted by electron beam to 61-75 Gy. RESULTS: The mean value of TRR-45 for all patients was lower than that of NRR-45 for the 78 patients with metastatic neck nodes (70% +/- 4.8% vs. 81% +/- 5%, p = 0.003). The 3-year actuarial neck control rate was better than the primary tumor control rate with statistical significance (98% vs. 85%, p = 0.009). No significant statistical differences concerning local control probability, nodal control probability, or survival rate were found among patients with slow, moderate, or rapid TRR-45 or NRR-45. T-stage was the only significant prognostic factor for locoregional control after multivariate analysis. Tumor volume and T-stage were found to have a statistically significant negative correlation with TRR-45. No associated factor was found to be significantly correlated with NRR-45. CONCLUSION: Slow regression rates of the primary tumor or neck nodes in NPC after receiving 45 Gy of irradiation do not mean ultimately poor radiocurability, but may merely imply slow clearance of the cells damaged during irradiation. The different radiobiological behaviors of the regression rates during treatment, ultimate control probabilities, or associated factors for regression rates of NPC between primary tumors and neck nodes need to be further investigated.

Intratumoral regional differences of DNA ploidy of gastrointestinal stromal tumors: a flow cytometric study.

BACKGROUND: Mesenchymal neoplasms of the gastrointestinal tract remain controversial in regard to both diagnostic criteria and prognostic factors. In order to investigate whether DNA ploidy in a single area of a tumor can be representative of the entire tumor, multiple samples from the same tumor were analyzed in 79 cases of gastrointestinal stromal tumors. METHODS: Forty-three male and 36 female patients, aged 11 to 80 years with stromal tumors of the GI tract were selected. Flow cytometric DNA ploidy analysis was done on tissue cut from paraffin blocks by using the modified technique of Hedley et al. RESULT: All 34 benign stromal tumors displayed a concordant diploid DNA content. Eighteen (40%) of the 45 malignant stromal tumors (13 low-grade, 5 high-grade) were diploid. Aneuploid and polyploid DNA stemlines were found in 10 cases (43.4%) of low-grade stromal tumors, and in 17 cases (77.2%) of high-grade stromal tumors. DNA polyploidy was identified in 21 (46.7%) of 45 malignant stromal tumors. Also, aneuploid populations were accompanied by diploid populations. CONCLUSION: DNA content correlated well with histologic category. Tumor aneuploidy was more frequently seen in tumors of advanced stage, but no relationship was seen between tumor stage and the presence of tumor heterogeneity. Differences in ploidy levels were thus not necessarily associated with apparent differences in histologic patterns. The mechanism responsible for regional differences in DNA ploidy in the same tumor remain unexplained. Several hypotheses are reviewed.

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.

Dermatofibrosarcoma protuberans: treatment results of 35 cases.

BACKGROUND AND PURPOSE: This study evaluates the treatment results of patients with dermatofibrosarcoma protuberans. PATIENTS AND METHODS: Between August 1987 and July 1998, 35 consecutive patients with pathologically proved dermatofibrosarcoma protuberans received surgery with or without radiation therapy. Their treatment results were analyzed retrospectively. RESULTS: The patient ages ranged from 5 to 67 years (median 37 years). There were 24 males and 11 females. The anatomic sites of tumor were: trunk in 21, extremity in eight, and head and neck region in six. The maximal dimension of tumor ranged from 1.5 to 25 cm. Surgery techniques included local excision and wide excision with or without graft or flap. Adjuvant radiation therapy was given to 11 patients, with a dose ranging from 46 to 68 Gy (one pre-operative, ten post-operative). At a median follow-up of 50 months (range 11-131 months), there were 11 patients (nine patients without radiation therapy) who developed local failure. Salvage therapy (excision with or without radiation therapy) was given to all of them, and ten achieved disease control. Some patients had treatment-related moderate cosmetic or functional problems. CONCLUSIONS: Dermatofibrosarcoma protuberans is a malignancy of a high cure rate, and adjuvant radiation therapy can reliably decrease the local recurrence rate and prevent mutilation and functional deficit caused by repeated surgery.

Healing of superior vena cava defect in mediastinal seminoma with invasion.

We present an unusual case of mediastinal seminoma with direct intraluminal invasion into the superior vena cava (SVC) and extension to the right atrium. Magnetic resonance imaging demonstration of the SVC defect due to tumor invasion was important for determining treatment strategy because rapid posttherapeutic tumor regression may increase the risk of SVC rupture. Gradual healing of the SVC defect at the tumor entrance site was attained using a tailored treatment plan with radiotherapy and chemotherapy.

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.

Postoperative radiotherapy for supratentorial malignant gliomas.

From January 1988 to December 1996, sixty-five patients with histologically confirmed supratentorial malignant gliomas were treated with postoperative radiation therapy in our department. They were subjected to this analysis according to different clinical and pathologic parameters. The overall 1-year, 2-year survival rate was 57% and 23%, respectively. With univariate analysis, age, postoperative Karnofsky performance status, duration of symptoms, multiplicity of lesions and the extent of surgery were identified as significant prognostic factors. With multivariate analysis, postoperative Karnofsky performance status and the extent of surgery continued to show independent prognostic significance on overall survival.

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.

Computed tomography findings of bony regeneration after radiotherapy for nasopharyngeal carcinoma with skull base destruction: implications for local control.

PURPOSE: To evaluate the response of bony destruction (BD) of the skull base following radiotherapy in nasopharyngeal carcinoma (NPC) and investigate the implications of bony regeneration (BR) on local control and its related factors. METHODS AND MATERIALS: Ninety patients with NPC with skull base destruction clearly demonstrated on computed tomography (CT) were reviewed. These patients have completed the prescribed treatment and received regular CT follow-up. A total of 338 sets of CT images of the head and neck were reviewed. The tumor response and the appearance of BR in the previous destructive part of the skull base were recorded and analyzed. The tumor response was divided into complete, partial, or no response. BR was defined as recalcification or sclerotic change with partial or complete healing in the previous osteolytic bony defect. Local failure was confirmed either by pathological or merely by imaging studies showing progression of tumor in consecutive radiological pictures. RESULTS: The distribution of specific sites of bony destruction (BD) in these patients included the sphenoid bone (68%), paracavernous sinus area (48%), petrous apex (47%), clivus (44%), pterygoid plates (20%), and others (7%). The CT showed 57 patients (63%) had BR. All were observed within 1 year after treatment. Sixty-two patients (69%) had complete tumor response after treatment. Analyzed by logistic regression method, tumor response after treatment was found to have a statistically significant correlation with BR (p = 0.0004). Most BR (55/57) was demonstrated in patients with complete tumor response. The 3-year actuarial local control rate was 54 % in these patients. The local control was quite different in the comparison of patients with BR versus those with persistent BD (77% vs. 21%, p < 0.0001). Multivariate analysis showed that patients with complete tumor response or with BR on imaging had statistically better local control than those without either of the two findings (p < 0.05). CONCLUSION: Appearance of BR at previous destructive skull base following radiotherapy for NPC patients could be clearly demonstrated on CT. Bony regeneration significantly correlated with treatment response and local control. Although the underlying significance of BR was unknown, to predict the outcome after treatment, the appearance of BR shown on CT may imply the complete eradication of tumor in this area.

Local vaginal anesthesia during high-dose-rate intracavitary brachytherapy for cervical cancer.

PURPOSE: To evaluate the clinical efficacy of local vaginal lidocaine application for pain relief during high-dose-rate (HDR) intracavitary brachytherapy for patients with cervical cancer, and to investigate sequential changes in serum levels of lidocaine during the procedures. METHODS AND MATERIALS: This prospective study was designed to examine the analgesic effect, physical response, and side effects of local anesthesia during HDR intracavitary brachytherapy. Forty patients were enrolled. All patients received 10-15 MV X-rays to the pelvis with a total dose of 45-59.4 Gy 5-6 weeks before undergoing HDR intracavitary brachytherapy. All patients underwent first intracavitary brachytherapy under general anesthesia. These patients were randomly allocated to receive one of two different treatment protocols as follows: (1) treatment session - control session - treatment session - control session; or (2) control session - treatment session- control session - treatment session. In the treatment sessions, topical anesthesia was administered using 4 ml of 10% lidocaine solution sprayed liberally on the cervix and vagina during intracavitary brachytherapy. In the control sessions, a placebo was administered in the same manner during brachytherapy. The Hensche's applicators for brachytherapy were inserted into the cervix and vagina 5 min after lidocaine application. The visual analogue scale (VAS) was used to assess pain and discomfort during brachytherapy. Blood pressure and heart rates were measured to evaluate the physiological response. Another prospective study was then performed to investigate the sequential changes of serum lidocaine levels during the anesthetic procedure. Eleven additional patients with similar disease state and demographic characteristics were enrolled and blood samples were obtained before, and 5, 15, 30, and 45 min after the initiation of lidocaine application. RESULTS: The mean VAS values recorded during the treatment sessions and control sessions were 49.9 +/- 24.1 versus 60.1 +/- 24.8, respectively. The value of VAS in the treatment session was significantly lower than that of the control session (p < 0.001). No statistically significant differences were found in the changes of blood pressure and heart rate and in the incidence of side effects during these two types of sessions (p > 0.05). In the drug-level study, serum levels of lidocaine reached a peak 5 min after the initiation of local anesthesia. The mean peak concentrations (Cmax) of lidocaine were 0.50 +/- 0.45 microg/ml. CONCLUSION: Local vaginal anesthesia with 10% lidocaine solution can significantly decrease the degree of painful sensation during HDR intracavitary brachytherapy, and is safe to administer for the procedure for cervical cancer.

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.

Impact of the extent of parametrial involvement in patients with carcinoma of the uterine cervix.

PURPOSE: A scoring system is proposed to measure the extent of parametrial involvement and predict treatment outcome in patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: 244 patients with FIGO Stage IIB (n = 146) or IIIB (n = 98) carcinoma of the uterine cervix were treated by radical radiotherapy from October 1987 to June 1992. Impact of the extent of parametrial involvement on outcome was studied. All patients were scored by the newly introduced scoring system described as follows: score 1, tumor extending <1/2 the distance to the pelvic side wall; score 2, tumor extending >1/2 the distance to the pelvic side wall but not to pelvic side wall; score 3, tumor extending to the pelvic side wall. The score in each patient was defined as the sum of the scores of both the left and right parametrial tumor extent. RESULTS: There were 53, 47, 61, 34, 25, and 24 patients in score 1, 2, 3, 4, 5, and 6, respectively. All 244 patients were subdivided into three groups described as follows: score 1 and 2, group I; score 3 and 4, group II; score 5 and 6, group III. In univariate analysis, lower score groups had better overall survival rate (OS), disease-free survival rate (DFS), local control rate (LC), and distant metastasis-free rate (DMF) than higher score groups including groups I vs. II, II vs. III, or I vs. III. The differences were all statistically significant except for the difference of the DMF in group I vs. II. In multivariate analysis, score (range 1-6) was also statistically significant in OS (p < 0.0001), DFS (p = 0.0015), LC (p = 0.0032), and DMF (p = 0.0141). CONCLUSIONS: The data suggested that the new scoring system defined by pelvic examination is a convenient, simple, and reliable method of measuring the degree of parametrial extension and predicting the outcome of patients with parametrial disease.

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.

Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment results and prognostic factors.

BACKGROUND: Reports on locoregional control and survival of squamous cell carcinoma of buccal mucosa are scarce in literature. In this study, a single institutions's experience of combined surgery and postoperative radiotherapy (RT) for buccal mucosal malignancy with favorable results was analyzed and presented. The prognostic factors on locoregional control were also discussed. METHODS: From January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal mucosa treated by surgery and RT were reviewed. The distributions according to American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III, 21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45 Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage, histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony structures, and regional lymph nodes) and treatment-related factors (surgical margin, radiation dose, and the time interval between operation and RT) were analyzed to determine their influence on locoregional control. RESULTS: Three-year actuarial locoregional control rate, overall survival rate, and disease-specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22 patients (45%) with recurrent tumors were reoperated, but only 2 patients were successfully salvaged. Positive surgical margin and tumor invasion to skin of cheek were significantly poor prognostic factors on locoregional control by univariate analysis. In multivariate analysis, tumor invasion to skin of cheek was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was the major cause of death for squamous buccal mucosa cancers managed with surgery and RT. Few recurrences could be detected early and successfully salvaged. Skin of cheek involvement is an important prognostic factor for buccal mucosa cancers.