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PubMed1996

The role of radiotherapy in the management of extrahepatic bile duct cancer: an analysis of 145 consecutive patients treated with intraluminal and/or external beam radiotherapy.

PURPOSE: To determine the feasibility of high dose radiotherapy and to evaluate its role in the management of extrahepatic bile duct (EHBD) cancer. METHODS AND MATERIALS: Between 1983 and 1991, 145 consecutive patients with EHBD cancer were treated by low dose rate intraluminal 192Ir irradiation (ILRT) either alone or in combination with external beam radiotherapy (EBRT). Among the primarily irradiated, 77 patients unsuitable for surgical resection, 54 were enrolled in radical radiotherapy, and 23 received palliative radiotherapy. Fifty-nine received postoperative radiotherapy, and the remaining 9 preoperative radiotherapy. The mean radiation dose was 67.8 Gy, ranging from 10 to 135 Gy. Intraluminal 192Ir irradiation was indicated in 103 patients, and 85 of them were combined with EBRT. Expandable metallic biliary endoprosthesis (EMBE) was used in 32 primarily irradiated patients (31 radical and 1 palliative radiotherapy) after the completion of radiotherapy. RESULTS: The 1-, 3-, and 5-year actuarial survival rates for all 145 patients were 55%, 18%, and 10%, for the 54 patients treated by radical radiotherapy (mean 83.1 Gy), 56%, 13%, and 6% [median survival time (MST) 12.4 months], and for the 59 patients receiving postoperative radiotherapy (mean 61.6 Gy), 73%, 31%, and 18% (MST 21.5 months), respectively. Expandable metallic biliary endoprosthesis was useful for the early establishment of an internal bile passage in radically irradiated patients and MST of 14.9 months in these 31 patients was significantly longer than that of 9.3 months in the remaining 23 patients without EMBE placement (p < 0.05). Eighteen patients whose surgical margins were positive in the hepatic side bile duct(s) showed significantly better survival compared with 15 patients whose surgical margins were positive in the adjacent structure(s) (44% vs. 0% survival at 3 years, p < 0.001). No survival benefit was obtained in patients given palliative or preoperative radiotherapy. Gastroduodenal complications increased in those receiving doses of 90 Gy or more, and serious biliary bleeding was experienced in three preoperatively irradiated patients. Complications in other patients was tolerable. CONCLUSIONS: High-dose radiotherapy, consisting of ILRT and EBRT, appears to be feasible in the management of EHBD cancer, and it offers a survival advantage for patients not suited for surgical resection and patients with positive margins in the resected end of the hepatic side bile duct. Expandable metallic biliary endoprosthesis assists the internal bile flow and may lengthen survival after high dose radiotherapy.

Adult↗
PubMed2004

A randomised clinical trial of radiotherapy plus cisplatin versus radiotherapy alone in stage III non-small cell lung cancer.

This study was designed to compare high-dose fractionated radiotherapy alone versus the same radiotherapy plus cisplatin in stage III non-small cell lung cancer (NSCLC). We randomly assigned 176 patients with stage III non-small cell lung cancer to one of two treatments; fractionated radiotherapy alone at dose of 64 Gy for 6-7 weeks (2 Gy given 32 times, in five fractions a week) or radiotherapy in the same schedule, combined with 20mg/m2 cisplatin 1 h before radiotherapy, given on days 1-5 of the second and sixth treatment weeks. The frequency of loco-regional progression was 68% among the patients who received radiotherapy plus cisplatin and 86% among those who received radiotherapy alone (P = 0.0001). The probability of survival free of disease after 3 years was 10% among the patients assigned to radiotherapy plus cisplatin and 0% among those treated only with radiotherapy (P = 0.0006). Overall survival at 3 years was 10% among those given radiotherapy plus cisplatin and 2% among those who received radiotherapy alone (P = 0.00001). Multivariate analysis demonstrated that radiotherapy plus cisplatin significantly improved loco-regional progression-free survival and overall survival, irrespective of radiation dose. The addition of cisplatin to fractionated radiotherapy prolongs loco-regional progression-free interval and survival in stage III non-small cell lung cancer.

Aged↗
PubMed2004

A meta-analysis of randomised trials suggests a survival benefit for combined radiotherapy and radical cystectomy compared with radical radiotherapy for invasive bladder cancer: are these data relevant to modern practice?

OBJECTIVE: Treatment options for muscle-invasive bladder cancer include radical cystectomy or radical radiotherapy, and the prevailing choice varies by country. The ideal treatment would be a bladder-preserving therapy without compromising survival. The objective of this review was to compare the overall survival after radical surgery (cystectomy) with radical radiotherapy in patients with muscle-invasive cancer. MATERIALS AND METHODS: We searched the Cochrane Controlled Trials Register, Medline, EMBASE, Cancerlit, Healthstar and the Database of Abstracts of Reviews of Effectiveness. Authors of unpublished data were contacted. Randomised trials comparing surgery (alone or with preoperative radiotherapy) with radiotherapy were eligible for assessment. Three reviewers assessed trial quality based on the Cochrane Guidelines. Data were extracted from the text of the article or extrapolated from the Kaplan-Meier plot. The Peto odds ratio was determined to compare the overall survival and disease-specific survival. Analysis was performed on an intention-to-treat basis and treatment actually received. RESULTS: No randomised trials comparing surgery alone with radiotherapy alone were identified. Three randomised trials comparing preoperative radiotherapy followed by radical cystectomy (surgery) versus radical radiotherapy with salvage cystectomy (radical radiotherapy) were eligible for assessment. These trials represented a total of 439 patients, 221 randomised to surgery and 218 to radical radiotherapy. Three trials were combined for the overall survival results, and one was evaluable for the disease-specific survival analysis. The mean overall survival (intention-to-treat analysis) at 3 and 5 years were 45% and 36% for surgery, and 28% and 20% for radiotherapy, respectively. Peto odds ratio (95% confidence interval [CI]) analysis consistently favoured surgery in terms of overall survival. The results were significantly in favour of surgery at 3 years (OR = 1.91, 95% CI 1.30-2.82) and at 5 years (OR = 1.85, 95% CI 1.22 -2.82). On a treatment-received basis, the results were significantly in favour of surgery at 3 years (OR 1.84, 95% CI 1.17-2.90) and 5 years (OR 2.17, 95% CI 1.39-3.38) for overall survival, and at 3 years (OR 1.96, 95% CI 1.06-3.65) for disease-specific survival. CONCLUSIONS: The analysis of this review suggests that there is an overall survival benefit with combined preoperative radiotherapy plus radical surgery compared with radical radiotherapy plus salvage cystectomy in patients with muscle-invasive bladder cancer. However, it must be considered that only three trials were included for analysis, the patient numbers were small and that many patients did not receive the treatment they were randomised to. It must also be noted that many improvements in radiotherapy and surgery have taken place since the initiation of these trials; therefore, the data may not be readily extrapolated to modern practice. Ideally, a new trial comparing modern bladder-sparing therapy with the latest surgical approach to this disease is required.

Cystectomy↗
PubMed1992

A randomized trial comparing platinum-based chemotherapy followed by radiotherapy vs. radiotherapy alone in patients with locally advanced cervical cancer.

Seventy-one patients with stage IIb-IVa cervical cancer were entered on a randomized trial comparing standard pelvic radiotherapy vs. 3 cycles of combination chemotherapy with cisplatin, vinblastine and bleomycin followed by pelvic radiotherapy. Four out of 34 patients randomized to PVB followed by radiotherapy received no PVB and a further 3 patients had only one or 2 cycles of chemotherapy prior to radiotherapy due to drug-related toxicity or progressive disease. After a median follow-up of 3.1 years, no significant difference in survival has emerged between the two randomized groups. However, a difference in the pattern of relapse is emerging with a relatively reduced frequency of systemic relapse in patients receiving chemotherapy prior to local radiotherapy compared to radiotherapy alone. Tumor response was seen following PVB treatment and prior to radiotherapy in 47% of patients. Overall the tumor response rate following completion of radiotherapy was 89% in those treated by radiotherapy and 94% after PVB+radiotherapy. Thirty-three percent of patients randomized to radiotherapy alone relapsed first at a distant (extra pelvic site), and only 18% of patients randomized to initial PVB followed by radiotherapy relapsed systemically initially. When results are presented according to treatment actually given, these trends in patterns of treatment failure are magnified. No treatment-related deaths were reported, and there was no excess of complications with pelvic radiotherapy in the group who had received prior PVB chemotherapy.

Journal Article↗
PubMed1996

Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck.

BACKGROUND: In 1992, we reported the first analysis of a randomized trial comparing alternating radiotherapy and chemotherapy with radiotherapy alone in the treatment of squamous cell carcinoma of the head and neck. The results of that 3-year analysis indicated that the combined treatment had superior efficacy. PURPOSE: After an additional 2 years of follow-up, we again compared the efficacy of the two treatment regimens, with attention paid to differences in overall survival, progression-free survival, and locoregional relapse-free survival. METHODS: One hundred fifty-seven patients with untreated, unresectable squamous cell carcinoma of the head and neck were randomly assigned to receive either chemotherapy (four courses of cisplatin [20 mg/m2] and fluorouracil [200 mg/m2], given daily for 5 consecutive days during weeks 1, 4, 7, and 10) plus radiotherapy (three courses of 20 Gy each, given in fractions of 2 Gy per day during weeks 2-3, 5-6, and 8-9) or radiotherapy alone (70 Gy total dose, given in fractions of 2 Gy per day, 5 days per week). Eighty patients received the combined therapy, and 77 were treated with radiotherapy alone. Responses, failures, and toxic effects associated with the two treatment regimens were compared. Overall survival, progression-free survival, and locoregional relapse-free survival were calculated according to the Kaplan-Meier method; the logrank test was used to compare survival parameters between the two patient groups. Reported P values are two-sided. RESULTS: As reported previously, toxic effects associated with the combined therapy included both chemotherapy- and radiotherapy-related effects; however, the incidence and severity of mucositis were nearly identical among patients in the two treatment arms. The combined treatment was associated with a statistically significant increase in the frequency of complete response (i.e., the disappearance of clinically detectable disease for at least 4 weeks) (43% for the combined-treatment group compared with 22% for the radiotherapy-only group; P = .037, chi-squared test). Five-year estimates of overall survival in the combined-treatment group compared with the radiotherapy-only group were 24% (95% confidence interval [CI] = 14%-40%) and 10% (95% CI = 4%-24%), respectively (P = .01, logrank test). The estimates of progression-free survival at 5 years in the combined-treatment group compared with the radiotherapy-only group were 21% (95% CI = 11%-37%) and 9% (95% CI = 3%-22%), respectively (P = .008, logrank test). Finally, the 5-year estimates of locoregional relapse-free survival were 64% (95% CI = 36%-84%) in the combined-treatment group and 32% (95% CI = 10%-65%) in the radiotherapy-only group (P = .038, logrank test). CONCLUSIONS AND IMPLICATIONS: The superiority of alternating chemotherapy and radiotherapy over radiotherapy alone in treating unresectable squamous cell carcinoma of the head and neck seen at 3 years was confirmed at 5 years. However, additional trials must be conducted before considering the combined approach as standard therapy.

Antimetabolites, Antineoplastic↗
PubMed1992

Endometrial carcinoma in patients aged 75 years or older: outcome and complications after postoperative radiotherapy or radiotherapy alone.

A retrospective analysis is reported of 89 patients at least 75 years old (median age 79 years) treated with irradiation for endometrial carcinoma between 1972 and 1989, the median follow-up being 39 months. In 66 patients radiotherapy was given postoperatively and in one case preoperatively, 22 patients were treated with radiotherapy alone: intravaginal insertions exclusively in 22 patients (median dose 60 Gy to the mucosa) and combined with external radiotherapy in 53 patients (median external target dose 45 Gy; three or four fields, all treated daily, 1.8 to 2.0 Gy per fraction, five fractions per week; 30 Gy to the vaginal mucosa with low-dose rate). A few patients were treated with external radiotherapy or intrauterine insertions only. 65% of the patients treated with radiotherapy alone and 34% of the patients receiving postoperative radiotherapy had FIGO stage II or III disease. Five-year actuarial overall survival and disease-free survival for all patients with adenocarcinomas treated with curative intent was 47.5% and 57.2%, respectively. In 48 patients with surgical stages I and II, treated with postoperative adjuvant radiotherapy, overall actuarial survival is 58.2% and disease-free survived 65.5% at five years. After postoperative vaginal insertions only, no vaginal recurrence occurred. With combined external and intravaginal radiotherapy in surgical stage I and II, 4/36 patients (11%) showed a recurrence in the vagina only, the abdominal and pelvic recurrence rate being 8.3%. Grade 3 to 4 late toxicity was observed in 6/53 patients (11.3%) treated with external and intravaginal radiotherapy. However, in patients receiving external radiotherapy less than 45 Gy and intravaginal radiotherapy 30 to 40 Gy, as is standard postoperative adjuvant treatment today, only one grade 3 late toxicity was observed in 17 patients (5.9%). We conclude, that treatment of elderly patients with adenocarcinoma of the uterus should follow the same pattern as in younger patients, the acute side-effects and late toxicity of radiotherapy being similar.

Actuarial Analysis↗
PubMed1993

Pituitary adenomas: long-term results for radiotherapy alone and post-operative radiotherapy.

PURPOSE: Analysis of prognostic factors and long-term results of treatment of pituitary adenomas. METHODS AND MATERIALS: The study involved a retrospective review of outcome in a series of 268 patients with pituitary adenomas, treated at the Queensland Radium Institute from January 1962 to December 1986. The study population included 108 patients treated with radiotherapy alone and 160 patients treated by surgery and post-operative radiotherapy. In each group, univariate and multivariate analyses were conducted of possible prognostic factors including age, sex, performance status, tumor type, tumor extent, visual disturbance, radiotherapy dose, and field size. RESULTS: For radiotherapy alone, the 10-year progression-free survival rate was 60%, and overall tumor control was obtained in 77%. Univariate analysis suggested that tumor type and radiotherapy field size were of prognostic significance. Multivariate analysis confirmed that Prolactinoma subtype and increasing radiotherapy field size were independently predictive of reduced progression-free survival. Long-term visual complications occurred in 1% of patients treated by radiotherapy alone. In patients treated by surgery and post-operative radiotherapy, the 10-year progression-free survival rate was 77%, and overall tumor control was achieved in 83%. Univariate analysis suggested that tumor type, completeness of surgical excision, and radiotherapy dose were predictive of outcome. However, on multivariate analysis, only the extent of surgical excision predicted prognosis independently. Long-term visual sequelae were noted in 3% of patients treated by surgery and post-operative radiotherapy. CONCLUSION: Both radiotherapy alone and post-operative radiotherapy are effective in long-term control of pituitary adenomas, and produce acceptably low complication rates.

Adenoma↗
PubMed2003

The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001--summary and conclusions.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) and published in 1996. The assessment reviewed the scientific literature up to 1993 on the use of radiotherapy in the treatment of solid tumours, and estimated the costs associated with radiotherapy. It also described the current practise of radiotherapy in Sweden 1992 and compared practise with scientific knowledge. The SBU has now conducted a follow-up study on radiotherapy for cancer, including a review of the scientific literature from 1994 and a prospective survey of radiotherapy practise in Sweden 2001. The following conclusions were drawn: The role of radiotherapy as an important form of treatment for cancer with both curative and palliative intent has been further confirmed. The use of radiotherapy in Sweden has increased and is now at the internationally recommended level. Radiotherapy in Sweden is mostly given in accordance with the scientific evidence but may still be underutilized in certain situations. The resources for radiotherapy are being utilized more efficiently. The costs of radiotherapy are still 5% of the total cost of cancer care, while the cost of an individual treatment (fraction) has decreased. The need for radiotherapy capacity will increase. In addition, half of the treatment equipment will have to be replaced in the next few years.

Female↗
PubMed1993

[Radiotherapy in adults with localized supradiaphragmatic stages CS I/II of Hodgkin's disease. 2. The special aspects of radiotherapy: dosage, fractionation, focal volumes, risks, conclusions].

For patients with Morbus Hodgkin and CS I/II of the low risk group and primary radiotherapy recommended treatment fields are: regional field for isolated high cervical involvement, mantle field for isolated mediastinal involvement and extended mantle field for the other patients. Omission of the infradiaphragmatic irradiation volume for PS I/II may be regarded as an advantage, which must be compared with the risk of a staging laparotomy, whereas the low risk of undertreatment of a small part of patients with CS I/II PS III probably does not outweigh the risk of the laparotomy. Equal efficacy of chemotherapy alone for these patients has not been proven sufficiently and important questions concerning long-term risks are unanswered. Ongoing studies will show, whether combinations with reduced chemotherapy or other types of chemotherapy and local radiotherapy are superior. Details of the mantle field borders and blocking are described. In most patients with adjuvant radiotherapy after complete remission after chemotherapy, the recommended target volume includes only the regions with proven involvement before chemotherapy. Details of the mediastinal treatment volume for patients with adjuvant radiotherapy after chemotherapy for bulky mediastinal disease are given. According to some recent analysis of a large body of dose-effect data, the recommended target doses in primary irradiation are between 36 and 40 Gy for regions with proven involvement and between 30 and 36 Gy for electively treated regions. The recommended target dose per fraction is between 1.5 and 1.8 Gy and less than 2 Gy in various critical tissues. According to the recent recommendations, the maximal total doses in mantle field radiotherapy to the spinal cord should be 38 Gy for radiotherapy alone and 36 Gy for radiotherapy combined with chemotherapy. The maximal total dose to the whole heart should be 15 Gy and for the other parts between 30 and 35 Gy. After chemotherapy with MOPP oder MOPP-like regimes, there is a cumulative risk of leukaemia between 2.2 and 11.9%. After radiotherapy alone, there is only a very low risk of leukaemia after radiotherapy and chemotherapy to the risk after chemotherapy. Most long-term studies show an increased risk of solid second malignancies associated with radiotherapy with a relative risk of approximately two. In the analyzed studies, the cumulative risk of solid second malignancy after seven to 15 years is between 7 and 11.2% after radiotherapy, between 7 and 11.7% after chemotherapy and between 7 and 11.7% after radiotherapy and chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1999

Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group.

BACKGROUND: Radiotherapy in addition to systemic treatment after mastectomy prolongs survival in high-risk breast-cancer patients. However, adjuvant radiotherapy has a potential association with ischaemic heart disease. We assessed morbidity and mortality from ischaemic heart disease in patients treated with postmastectomy radiotherapy. METHODS: Between 1982 and 1990, we randomly assigned 3083 women at high risk of breast cancer, after mastectomy, adjuvant systemic treatment with (n=1538) or without (n=1545) radiotherapy. An anterior photon field was used against the periclavicular region and the axilla. The chest wall was treated through two anterior shaped electron fields, one including the internal mammary nodes. The intended dose was 48-50 Gy in 22-25 fractions, at four to five fractions per week. We obtained information on morbidity and mortality of ischaemic heart disease over a median of 10 years. Analysis was by intention to treat. FINDINGS: More women in the no-radiotherapy group than in the radiotherapy group died of breast cancer (799 [52.5%] vs 674 [44.2%]), whereas similar proportions of each group died from ischaemic heart disease (13 [0.9%] vs 12 [0.8%]). The relative hazard of morbidity from ischaemic heart disease among patients in the radiotherapy compared with the no-radiotherapy group was 0.86 (95% CI 0.6-1.3), and that for death from ischaemic heart disease was 0.84 (0.4-1.8). The hazard rate of morbidity from ischaemic heart disease in the radiotherapy group compared with the no-radiotherapy group did not increase with time from treatment. INTERPRETATION: Postmastectomy radiotherapy with this regimen does not increase the actuarial risk of ischaemic heart disease after 12 years.

Adult↗
PubMed2004

Preoperative radiotherapy combined with intraoperative radiotherapy improve results of total mesorectal excision in patients with T3 rectal cancer.

PURPOSE: The survival advantage of preoperative radiotherapy in patients with rectal cancer is still a matter of debate, because its incremental benefit in the total mesorectal excision setting is unclear. This study was designed to evaluate early and long-term results of preoperative radiotherapy plus intraoperative radiotherapy in a homogeneous population of T3 middle and lower rectal cancer patients submitted to total mesorectal excision. METHODS: A series of 113 patients with middle and lower T3 rectal cancer consecutively submitted to total mesorectal excision at a single surgical unit from 1991 to 1997 were divided into two groups according to type of neoadjuvant treatment: preoperative radiotherapy (38 Gy) plus intraoperative radiotherapy (10 Gy; n = 69), and no preoperative treatment (total mesorectal excision; n = 44). Standard statistical analyses were used to evaluate early (downstaging, intraoperative factors, hospital morbidity, and mortality rates) and long-term results (recurrence and survival). RESULTS: Overall, 68.2 percent of patients were downstaged by the preoperative regimens (T0 specimens in 3 cases). Postoperative complications were comparable in the two groups. Five-year, disease-specific survival was 81.4 and 58.1 percent in preoperative radiotherapy plus intraoperative radiotherapy group and total mesorectal excision group, respectively (P = 0.052). Corresponding figures for disease-free survival were 73.1 and 57.2 percent in the two groups, respectively (P = 0.096). The rates of local recurrence at five years were 6.6 and 23.2 percent in preoperative radiotherapy plus intraoperative radiotherapy and total mesorectal excision groups, respectively (P = 0.017). CONCLUSIONS: Preoperative radiotherapy plus intraoperative radiotherapy associated with total mesorectal excision reduce local recurrence rate and improve survival in T3 rectal cancer compared with total mesorectal excision alone.

Adult↗
PubMed1999

Oxygenation of cervical cancers during radiotherapy and radiotherapy + cis-retinoic acid/interferon.

PURPOSE: We have evaluated the tumor tissue pO2 in cervical cancers during radiotherapy with special emphasis on the course of the pO2 in primarily hypoxic tumors and in patients treated with radiotherapy plus 13-cis-retinoic acid/interferon-alpha-2a. METHODS AND MATERIALS: From June 1995 through April 1997, 49 patients with squamous cell carcinoma FIGO IIB-IVA of the cervix who were treated with definitive radiotherapy with curative intent underwent polarographic measurement of tumor tissue pO2 with an Eppendorf pO2-histograph prior to and during radiation treatment. Radiotherapy consisted of external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus high dose rate (HDR) brachytherapy. Twenty-two patients had additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) and interferon-alpha-2a (IFN-alpha-2a). Therapy with cRA/IFN in these patients started 2 weeks before radiotherapy; during this induction period, cRA was administered in a dosage of 1 mg per kilogram body weight orally daily and IFN-alpha-2a in a dosage of 6x10(6) I.U. subcutaneously daily. After start of external radiotherapy (XRT), cRA/IFN was continued concomitantly with radiotherapy in reduced doses (0.5 mg cRA per kg body weight orally daily plus 3x10(6) I.U. IFN-alpha-2a subcutaneously three times weekly until the end of the radiation treatment). PO2 measurements were performed prior to radiotherapy, at 20 Gy, and at the end of radiotherapy. RESULTS: A poor oxygenation defined as a median pO2 of 10 mm Hg or less was present in 15/38 tumors (39%) in which measurements prior to any treatment were done. Low pO2 readings below 5 mm Hg were present in 70% of all tumors prior to treatment. In 13 of 15 hypoxic tumors, pO2 measurements at 19.8 Gy were performed. In these tumors, a significant increase of the median pO2 from 6.0+/-3.1 mm Hg to 20.7+/-21.2 mm Hg was found, p<0.01. The increase in the median pO2 was more pronounced in patients with radiotherapy plus additional cRA/IFN treatment as compared to patients treated with irradiation alone (median pO2 raised from 7.0+/-3.5 mm Hg to 40.9+/-21.3 mm Hg versus 5.7+/-3.1 mm Hg to 14.7+/-17.9 mm Hg). In a multivariate analysis, both the effect of radiation dose (pretreatment versus 19.8 Gy) and the type of treatment (XRT alone versus XRT plus cRA/IFN) had significant impact on the pO2 (P = 0.003 and p = 0.04). In patients with well-oxygenated tumors (pretreatment median pO2>10 mm Hg), 20/23 (87%) achieved a clinically complete response. In patients with primarily hypoxic tumors, 6/6 patients whose primarily hypoxic tumors showed an increase of the median pO2 above 10 mm Hg at 19.8 Gy achieved a complete remission (CR). In contrast, only 4/7 patients with a low pretreatment and persisting low median pO2 achieved a CR. CONCLUSIONS: There are evident changes in the oxygenation of cervical cancers during a course of fractionated radiotherapy. In primarily hypoxic tumors, a significant increase of the median pO2 was found. An additional treatment with cis-retinoic acid/interferon further improved the oxygenation. An impact of the different patterns of oxygenation on local control is to be evaluated.

Adult↗
PubMed2005

Outcome of accelerated radiotherapy alone or accelerated radiotherapy followed by exenteration of the nasal cavity in dogs with intranasal neoplasia: 53 cases (1990-2002).

OBJECTIVE: To compare long-term results of radiotherapy alone versus radiotherapy followed by exenteration of the nasal cavity in dogs with malignant intranasal neoplasia. DESIGN: Retrospective study. ANIMALS: 53 dogs with malignant intranasal neoplasia. PROCEDURE: All dogs underwent radiotherapy consisting of administration of 10 fractions of 4.2 Gy each on consecutive weekdays. For dogs in the surgery group (n=13), follow-up computed tomography was performed, and dogs were scheduled for surgery if persistent or recurrent tumor was seen. RESULTS: Perioperative complications for dogs that underwent surgery included hemorrhage requiring transfusion (2 dogs) and subcutaneous emphysema (8). Rhinitis and osteomyelitis-osteonecrosis occurred significantly more frequently in dogs in the radiotherapy and surgery group (9 and 4 dogs, respectively) than in dogs in the radiotherapy-only group (4 and 3 dogs, respectively). Two- and 3-year survival rates were 44% and 24%, respectively, for dogs in the radiotherapy group and 69% and 58%, respectively, for dogs in the surgery group. Overall median survival time for dogs in the radiotherapy and surgery group (477 months) was significantly longer than time for dogs in the radiotherapy-only group (19.7 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exenteration of the nasal cavity significantly prolongs survival time in dogs with intranasal neoplasia that have undergone radiotherapy. Exenteration after radiotherapy may increase the risk of chronic complications.

Animals↗
PubMedDate not supplied

Predictors of response to chemo-radiotherapy and radiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: The sensitivity of tumors to chemotherapy and radiotherapy differs from one case to another and may be influenced by the expression of biological molecules. The presence of six potential predictive markers in esophageal squamous cell carcinoma (ESCC) was investigated and the data obtained were related to the response of the tumors to chemo-radiotherapy and radiotherapy. MATERIALS AND METHODS: Biopsy specimens were obtained from 61 patients with ESCC before treatment with chemo-radiotherapy (31 patients) or radiotherapy (30 patients). External radiotherapy was delivered by a two-field technique to a total of 60-70 Gray. Concurrent chemotherapy consisted of cisplatin or nedaplatin and 5-fluorouracil administered intravenously. The patients were examined before and after treatment by endoscopy, esophagography and computed tomography. The clinical response was classified as effective (> 50% decrease in primary lesion), or ineffective. Immunohistochemical staining for p53, p21, bax, bcl2, heat-shock protein (Hsp) 27 and Hsp70 was performed on the biopsy specimens before therapy. RESULTS: The primary tumor response was effective in 73.8% (45/61) and ineffective in 26.2% (16/61) of patients. Tumors with p53-positive expression were less sensitive than p53-negative tumors (p = 0.033). p21-positive patients (p = 0.027), and Hsp27-negative (p = 0.0057) and Hsp70-negative patients (p = 0.010) were all good responders. Neither bcl2 nor bax expression was related to the efficacy of therapy. Multivariate analysis revealed that Hsp27 was the most reliable predictor of the effect of chemo-radiotherapy and radiotherapy among the four potential markers. p53-negative and Hsp70-negative patients had a more favorable prognosis than p53- and Hsp70-positive patients (p = 0.039, p = 0.038, respectively). CONCLUSION: Expression of Hsp27 was a good predictor of the response of ESCC to chemo-radiotherapy and radiotherapy.

Adult↗
PubMed2000

Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91.

PURPOSE: The German Society of Pediatric Hematology and Oncology (GPOH) conducted a randomized, prospective, multicenter trial (HIT '91) in order to improve the survival of children with medulloblastoma by using postoperative neoadjuvant chemotherapy before radiation therapy as opposed to maintenance chemotherapy after immediate postoperative radiotherapy. METHODS AND MATERIALS: Between 1991 and 1997, 158 patients were enrolled and 137 patients randomized. Seventy-two patients were allocated to receive neoadjuvant chemotherapy before radiotherapy (arm I, investigational). Chemotherapy consisted of ifosfamide, etoposide, intravenous high-dose methotrexate, cisplatin, and cytarabine given in two cycles. In arm II (standard arm), 65 patients were assigned to receive immediate postoperative radiotherapy, with concomitant vincristine followed by 8 cycles of maintenance chemotherapy consisting of cisplatin, CCNU, and vincristine ("Philadelphia protocol"). All patients received radiotherapy to the craniospinal axis (35.2 Gy total dose, 1.6 Gy fractionated dose / 5 times per week followed by a boost to posterior fossa with 20 Gy, 2.0 Gy fractionated dose). RESULTS: During chemotherapy Grade III/IV infections were predominant in arm I (40%). Peripheral neuropathy and ototoxicity were prevailing in arm II (37% and 34%, respectively). Dose modification was necessary in particular in arm II (63%). During radiotherapy acute toxicity was mild in the majority of patients and equally distributed in both arms. Myelosuppression led to a mean prolongation of treatment time of 11.5 days in arm I and 7.5 days in arm II, and interruptions in 35% of patients in arm I. Quality control of radiotherapy revealed correct treatment in more than 88% for dose prescription, more than 88% for coverage of target volume, and 98% for field matching. At a median follow-up of 30 months (range 1.4-62 months), the Kaplan-Meier estimates for relapse-free survival at 3 years for all randomized patients were 0.70+/-0.08; for patients with residual disease: 0.72+/-0.06; without residual disease: 0.68+/-0.09; M0: 0.72+/-0.04; M1: 0.65+/-0.12; and M2/3: 0.30+/-0.15. For all randomized patients without M2/3 disease: 0.65+/-0.05 (arm I) and 0.78+/-0.06 (arm II) (p < 0.03); patients between 3 and 5.9 years: 0.60+/-0.13 and 0.64+/-0.14, respectively, but patients between 6 and 18 years: 0.62+/-0.09 and 0.84+/-0.08, respectively (p < 0.03). In a univariate analysis the only negative prognostic factors were M2/3 disease (p < 0.002) and an age of less than 8 years (p < 0.03). CONCLUSIONS: Maintenance chemotherapy would seem to be more effective in low-risk medulloblastoma, especially in patients older than 6 years of age. Neoadjuvant chemotherapy was accompanied by increased myelotoxicity of the subsequent radiotherapy, causing a higher rate of interruptions and an extended overall treatment time. Delayed and/or protracted radiotherapy may therefore have a negative impact on outcome. M2/3 disease was associated with a poor survival in both arms, suggesting the need for a more intensive treatment. Young age and M2/3 stage were negative prognostic factors in medulloblastoma, but residual or M1 disease was not, suggesting a new stratification system for risk subgroups. High quality of radiotherapy may be a major contributing factor for the overall outcome.

Adolescent↗
PubMed1997

Comparison of accelerated hyperfractionated radiotherapy and conventional radiotherapy for supratentorial malignant glioma.

Between 1988 and 1993, 71 patients with glioblastoma or anaplastic astrocytoma were treated either with accelerated hyperfractionation radiotherapy (1.5 Gy twice daily to a total dose of 69 Gy, n = 35) or with conventional fractionation radiotherapy (1.8 Gy daily to 64.8 Gy, n = 36). Two patients in each group did not complete radiotherapy, leaving 67 evaluable. All patients received the chemotherapeutic regime ACNU intraarterially (50 mg/m2) or intravenously (100 mg/m2) prior to and after radiotherapy. Between 1990 and 1992, 19 patients also received intravenous interferon-beta (3 x 10(6) U, three times weekly) during radiotherapy. The median survival time was 14.5 months for the accelerated hyperfractionation group and 14 months for the conventional fractionation group. The median time to progression was 12 months for the accelerated hyperfractionation group and 9.5 months for the conventional fractionation group. There was no significant difference in either survival (P = 0.89) or progression-free survival (P = 0.25) between the accelerated hyperfractionation and conventional fractionation groups. Interferon therapy was associated with poorer survival. Brain necrosis developed in four out of 10 patients receiving accelerated hyperfractionation radiotherapy plus interferon-beta, but in none of nine patients receiving conventional fractionation radiotherapy plus interferon (P = 0.033). In conclusion, our study failed to demonstrate any possible benefit of accelerated hyperfractionation radiotherapy for malignant glioma. The incidence of brain necrosis may be increased by combining accelerated hyperfractionation radiotherapy and interferon-beta.

Adult↗