Reirradiation for recurrent head and neck carcinoma.

PURPOSE: To present the outcome and toxicity profile of reirradiation (re-RT) in patients with recurrent head and neck cancer (HNC). METHODS: From 1995 to 2009, 35 patients underwent re-RT at our institution. Twenty-seven (77%) patients were initially diagnosed with stage III/IV disease. The median total doses of irradiation -first and second courses- were 66.0 Gy (range 54.0-70.0) and 55.8 Gy (range 32.5-66.6), respectively. The median time from the first course of irradiation to re-RT was 25.2 months (range 8-136). Six (17%) patients underwent salvage surgery before reirradiation. Concurrent chemotherapy was administered to 18 (51%) patients. RESULTS: With a median follow-up of 12.9 months (range 2.5-109.6), the 1- and 2-year locoregional control (LRC) rates were 41 and 9%, respectively. The 1- and 2-year disease free survival (DFS) rates were 30 and 7%, respectively. The 1- and 2-year overall survival (OS) rates were 42.9 and 7.9%, respectively. Grade 3 acute toxicity was reported in 7 (20%) patients while grade 3-4 late radiation-induced complications were seen in 8 (23%) patients. In univariate analysis, an improvement in OS was observed in patients with initial N0/N1 stage vs. those with N2/N3 stage (p=0.004). Prior neoadjuvant chemotherapy was associated with significantly inferior OS (p=0.028), while neoadjuvant chemotherapy in recurrence was predictive of improved LRC (p=0.041). CONCLUSION: re-RT in HN cancer is associated with poor prognosis, especially in patients with inoperable disease. Complications due to treatment are not infrequent. Nonetheless, our outcomes remain encouraging and applicable to a carefully selected patient population.

Radiotherapy for Hodgkin's lymphoma: too hard to die?

The treatment of Hodgkin's lymphoma (HL) is associated with significant toxicity. The objective of high quality management is to keep the concept of combined modality, while trying to decrease the radiation dose, to diminish to a great extent the irradiated volume and at the same time to reduce the number of chemotherapy courses, introducing the so-called optimisation. New directives should be followed to obtain more effective treatments of HL. Shorter cycles of chemotherapy and the utilization of modern techniques in radiotherapy (RT) constitute fundamental steps to achieve this objective. Analysis of randomized studies supports the inclusion of reduced-field and dose of RT in the radiotherapeutic treatment options for HL. RT is an integral part of the combined-modality therapy (CMT) of HL.

External beam radiotherapy of bladder carcinoma: considerations in determining the irradiation field margins.

PURPOSE: Motions of the bladder and rectum during pelvic irradiation are considered as major causes of geometrical uncertainties. As a result, the volume status of these organs is changed and the definition of the treatment margins is imperative. The aim of this study was, firstly, to determine these margins, comparing series of CT scans, performed at simulation time, with empty (EB) and full bladder (FB) and, secondly, to evaluate the dose volume histograms (DVHs) of tumor and rectum using standard treatment margins. METHODS: Fifteen patients with muscle-invading urinary bladder carcinoma underwent two scan series with EB and FB bladder during radiotherapy (RT) simulation. Gross tumor volume (GTV), clinical target volume (CTV), planning treatment volume (PTV) and organs at risk (OAR) were contoured. Displacements of the bladder wall were determined at all directions. Cumulative DVHs were generated for the volumes of interest. Using the same beam arrangements for both the EB and FB CT series, DVHs were also produced. RESULTS: The mean bladder volume was 119.3±55.9 cm3 and 264.3±145.7 cm3 for EB and FB CT series, respectively (p<0.001). The maximum bladder wall displacement was observed at cranial direction (2.2±0.6 cm for the EB vs. 3.4±1.0 cm for the FB series; p<0.001) and at caudal direction (2.3±0.6 cm for the EB vs. 3.6±1.0 cm for the FB series; p<0.001). Standard anisotropic margins of 2 cm in craniocaudal and posterior-anterior directions and 1.2 cm in lateral direction gave coverage to 75% of all bladder movements caused by FB. Analysis of DVHs and tumor control probability (TCP) calculations gave same results (74%), while normal tissue complication probability (NTCP) of the rectum showed no significant changes. CONCLUSION: CT scans series with empty and full bladder, performed at simulation time, could offer a potential advantage to evaluate the target expansion necessary to cover the bladder wall for each patient, giving more information about safe margining.

Factors associated with outcome in liposarcomas of the extremities and trunk.

PURPOSE: Liposarcomas are malignant tumors that arise from primitive mesenchymal cells rather than mature adipose tissue. We aimed to evaluate the outcomes of patients with extremities and superficial trunk liposarcomas in relation to some clinicopathological factors. METHODS: Sixty-three surgically treated patients with liposarcoma, with mean age 53 years, were included in this study. The 5-and 10-year survival rates were analyzed with respect to local recurrences, distant metastases and death with the Kaplan-Meier method. Cox models estimated univariate and multivariate hazard ratios for each candidate predictor of interest. RESULTS: The 5-year overall survival was 77.8% (95% CI 65.5-87.3) and the 10-year overall survival was 63.5% (95% CI 50.4-75.3). The 5-and 10-year recurrence-free survival were 60% and 57%, respectively. The 5-and 10-year metastasis-free survival were 86% and 84%, respectively. In univariate analysis factors that were significantly associated with outcomes were grade III tumors, amputation procedures, use of chemotherapy and development of local recurrences. No significant association was observed in multivariate analysis. CONCLUSION: Patients with liposarcoma surviving for 5 years, have also a high probability to be alive at 10 years. The development of metastases is observed within the first 5-years from diagnosis. Metastatic disease after that period is rare. The possibility of local recurrence is not negligible after the 5th year of follow up.

The role of radiation dose in a combined therapeutic protocol for the prevention of heterotopic ossification after total hip replacement.

PURPOSE: To present the results of a prospective study which aimed to evaluate the efficacy of radiation dose in a combined protocol using postoperative radiotherapy (RT) and indomethacin for the prevention of heterotopic ossification (HO) in patients undergoing total hip arthroplasty (THA) and are at high risk for HO development. METHODS: Seventy-one patients with a mean age of 63 years received either a single dose of 7 Gy or a fractionated dose of 10 Gy in 5 fractions of 2 Gy within the 3 postoperative days. Concurrently all patients received 75 mg of indomethacin for 15 days. Patients were analysed for radiographical evidence of HO development and clinically with the Merle d'Aubigné score at 1 year. RESULTS: At 12 months combined RT and indomethacin achieved excellent prophylaxis of HO. The overall radiographical incidence of HO was 7.04% (95% CI 2.33-15.67), while no patient with clinically significant HO (Brooker III-IV) was seen. There was no statistically significant difference between the two RT protocols. In a subgroup of 12 patients with bilateral THA the incidence of HO in the non-irradiated hips was statistically significantly higher compared with the irradiated hips. All patients had improved joint mobility and function during follow up compared with the preoperative period. No statistically significant differences regarding the Merle d'Aubigné score was documented between the 2 RT groups. No acute or late side effects related to RT were noted. CONCLUSION: This study demonstrated the efficacy of combined RT and indomethacin in preventing heterotopic ossification after total hip arthroplasty. Fractionated total dose of 10 Gy seems to offer no further benefit compared to a single dose of 7.0 Gy.

Heterotopic ossification after total hip arthroplasty (THA) in congenital hip disease: comparison of two different prophylactic protocols.

INTRODUCTION: We aimed to evaluate retrospectively the efficacy of combined postoperative radiotherapy and indomethacin compared to indomethacin alone for the prevention of heterotopic ossification (HO) in high-risk patients with congenital disease of hip (CDH) undergoing total hip arthroplasty (THA). MATERIALS AND METHODS: Fifty-five patients received indomethacin alone (Group A), while 44 patients received the combined protocol (Group B). Patients >or=55 years were enrolled in Group B and those younger than 55 years in Group A. Patients were evaluated radiologically for the presence of HO 6 months after the operation. RESULTS: The incidence of HO in Group A was 34.5% (95% confidence interval 22.2-48.6%), while the respective incidence in Group B patients was 27.3% (95% CI 15.0- 42.8%). The difference was not statistically significant (p=0.5). No significant treatment-related side effects were reported. CONCLUSIONS: This is the first study evaluating the impact of HO prophylaxis in an immiscible population of patients with secondary arthritis due to CDH undergoing THA. Further future randomised evidence is required in order to ascertain the observed trend towards improved efficacy of the combined protocol for HO development.

Radical therapy for muscle-infiltrating bladder cancer (cystectomy or radiotherapy): does age affect the final therapeutic benefit for the patient?

PURPOSE: To evaluate the therapeutic outcome of radical cystectomy and radical radiotherapy in patients with T2N0M0 clinical stage bladder cancer in relation to their age. PATIENTS AND METHODS: Between 1995-2006, 119 patients with clinical stage T2N0M0 bladder cancer were treated with radical radiotherapy (group A) and were divided in 2 subgroups: >70 years old (A1) and 70 years old/B1 subgroup and

Combination chemotherapy with paclitaxel and gemcitabine followed by concurrent chemoradiotherapy in non-operable localized non-small cell lung cancer. A hellenic cooperative oncology group (HeCOG) phase II study.

UNLABELLED: Concurrent chemoradiotherapy has become a standard therapy for locoregionally advanced inoperable nonsmall cell lung cancer (NSCLC). The purpose of this phase II trial was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy following induction with non-platinum chemotherapy in patients with inoperable locally advanced NSCLC. PATIENTS AND METHODS: All patients with locally advanced inoperable NSCLC ECOG performance status (PS): 0-1 following staging received paclitaxel 200 mg/m2 in a 3-h infusion on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 every 21 days for two cycles. The patients with a response or stable disease (SD) continued to receive paclitaxel 60 mg/m2 weekly and radiotherapy 63 Gy given at 1.8 Gy once a day for 7 weeks. RESULTS: Forty-three eligible patients entered the study. The median age was 63 years (range 42-76), male 93%, IIIB 63% and IIIA 37%. Following induction 15 (36.5%) of the patients responded: complete response (CR), 2%; partial response (PR), 33%; and 19 (46.5%) SD. From those with SD, 7 (37%) improved to a PR following concurrent chemoradiotherapy. With a median follow-up of 44 months (95% CI: range 36-53) the median survival was 20.8 months (95% CI: range 15.4-26.3) and time-to-progression 8.4 months (95% CI: range 6.2-10.6). The median survival of those who had improved response from SD to PR was 31.4 months (95% CI: range 18.7-44.1) versus 20.8 months (95% CI: range 5.5-11.3) for those who had no improvement (p=0.20). The commonest grade 3/4 toxicity in induction was neutropenia 12% with 2 febrile neutropenic patients whereas in the concurrent chemoradiotherapy neutropenia, neurotoxicity and oesophagitis were observed in 6% of the patients. CONCLUSION: Concurrent chemoradiotherapy following induction chemotherapy in patients with stage III NSCLC is feasible with reasonable efficacy and acceptable toxicity.

Adjuvant chemo-radiotherapy in patients with gastric cancer.

BACKGROUND: The role of adjuvant therapy in gastric cancer has been controversial. AIM: In this study, we report our experience with adjuvant chemotherapy and radiotherapy in patients with non-metastatic gastric cancer. SETTINGS AND DESIGN: Fifty patients were reviewed and assigned to three therapeutic groups. MATERIALS AND METHODS: Twenty patients received radiotherapy with concomitant administration of 5-fluorouracil and leucovorin on the first and last three days of radiotherapy; 20 patients received a five-day cycle 5-fluorouracil and leucovorin followed four to five weeks later by radiotherapy concomitant with the administration of fluorouracil on the first and the last three days of radiotherapy. Four weeks after radiotherapy two more five-day cycles of chemotherapy were administered; 10 patients received three cycles of cisplatin/docetaxel followed by radiotherapy and three additional cycles of chemotherapy after the completion of radiotherapy. STATISTICAL ANALYSIS: Patients were evaluated for treatment-related toxicity, local recurrences, distant metastases and deaths. We also aimed to make any possible comparisons between different chemo-radiation protocols. RESULTS: Within a median follow-up of 21.5 months seven patients developed local recurrence and 17 patients developed distant metastases. The overall death proportion was 42% (95% CI 28.2-56.8%). Despite the limited number of patients, no statistically significant differences in local recurrences, distant metastases and deaths were observed between the three protocols. Acute and long-term treatment-related toxicity was low and no treatment-related deaths were observed. CONCLUSION: Despite variations of chemotherapy, our study demonstrated that combined chemo-radiotherapy for patients with resected gastric cancer can be administered safely, with acceptable toxicity.

Multi-focal gliosarcoma: a case report and review of the literature.

Gliosarcoma (GS) is an uncommon malignant brain tumor with biphasic tissue pattern consisted of both glial and sarcomatous components. It usually occurs in adult population of middle age. We report a rare case of multi-focal GS that was initially interpreted as metastases of extra-cranial tumor. The histological examination revealed the biphasic pattern of a GS. The patient was treated with postoperative external radiation therapy and had poor prognosis. To our knowledge this is the second published case of GS with multi-focal presentation. In this study we also review the literature on clinicopathological aspects of GS.

Patient and personnel dosimetry in endovascular radiotherapy with 90Sr/90Y sources.

Endovascular brachytherapy (EVBT) is an established treatment to reduce the probability of restenosis after a percutaneous coronary intervention. The purpose of this study was to assess (1) the manufacturer's stated dosimetric data for (90)Sr/(90)Y source trains to be used in EVBT and (2) the procedure-related radiation burden. The radiation fields in water around six (90)Sr/(90)Y source trains were studied using phantoms made of 'solid water' and MD55-2 radiochromic films. The water equivalence of the phantom material was tested by applying quantitative computed tomography. Thermoluminescence dosemeters were used to assess personal radiation burden and crosscheck the dose distribution along the source trains. Technical failure was observed in one source train and this train was excluded from analysis. The measured dose rate in water at 2 mm radial distance was on average 8% higher than the manufacture's stated value (range of measured to stated values 1.05--1.15). The dose rate decreased exponentially with radial distance between 2 and 6 mm. The dose rate in contact with the source viewing window of the delivery devices ranged between 0.5 and 7.5 mGy h(-1). Low-energy photons were the main contributors to personal dose.

Astrocytoma-like multiple sclerosis.

Multiple sclerosis (MS) may sometimes mimic clinically and radiologically a brain tumor. The initial recognition of such cases is essential as it might avoid a surgical intervention and supplementary treatment. However, even in patients who underwent surgery, the appropriate preparation of the specimen is of crucial importance for the correct pathological diagnosis since tumors and non-neoplastic demyelinating lesions share some common histopathological features. We present such a case of multiple sclerosis presenting with features of an astrocytoma and was treated with surgery and additional radiotherapy.

External radiation therapy for endometrial carcinoma: the University Hospital of Ioannina experience.

PURPOSE OF INVESTIGATION: The aim of our study was to present the experience of our department in the treatment of endometrial cancer with postoperative external beam radiotherapy (EBRT) without intracavitary brachytherapy (BRT) and to evaluate the efficacy of such a method. METHODS: We retrospectively retrieved the medical records of all patients with endometrial cancer treated with surgery and EBRT alone (median dose 50.0 Gy). Thirty-one women (median age: 67 years) of all clinical stages were reviewed and analyzed for recurrences (local or metastases) and late post-radiation side-effects. RESULTS: Within a median follow-up of 17 months one patient developed local recurrence and four developed metastases. Overall survival was 97% and disease-free survival was 87%. Three women developed post-radiation colitis. No other treatment-related late side-effects were observed. CONCLUSION: EBRT without BRT achieved an excellent local control in women with endometrial cancer although some of them were candidates for supplementary BRT.

Primary cerebral gliosarcoma: a case presentation with review of the literature.

In this presentation we describe a rare case of a 42- year-old female with a large right frontal gliosarcoma (GS) treated with gross total resection of the tumor and postoperative external radiotherapy. The patient did not respond to treatment and she died 3 months after the end of radio- therapy. We also present a review of the literature on epidemiology, pathogenesis, clinical presentation, diagnosis and treatment of this uncommon clinical entity.

Recurrent prostate cancer: the role of salvage postoperative external radiotherapy in low risk patients.

PURPOSE: The aim of this study was to present the Ioannina Radiation Therapy Department experience in the treatment of postoperative recurrent prostate cancer with postoperative external beam radiotherapy (EBRT) in initially low-risk patients for recurrence. PATIENTS AND METHODS: The medical records of all patients who underwent salvage postoperative EBRT for either biochemical or clinical local recurrence were reviewed. Primary endpoints were the incidence of clinical and biochemical recurrences, metastases and death. RESULTS: A total of 11 patients with biochemical recurrence were included. Four of them had clinical local recurrence as well. Postoperatively, all patients had pT1-T2N0M0 stage and therefore had low risk for recurrence. However, they were admitted for EBRT with recurrent disease with a mean pre-RT prostatic specific antigen (PSA) of 10 ng/ml. The daily dose of radiotherapy (RT) was 1.8 to 2.0 Gy and the median total dose was 64.8 Gy. All of the patients but one achieved PSA nadir value (<0.5 ng/ml) after RT. With a median follow up of 21 months (range 9-42 months), 5 (45.5%) patients had biochemical failure, 2 (18.18%) developed clinical local recurrence, one (9.1%) developed bone metastases and 2 (18.18%) died. No serious long-term toxicity was observed. CONCLUSION: Despite the small sample size of our study that precluded any further analyses on prognostic factors affecting outcomes after salvage EBRT, we achieved satisfactory results regarding local control of disease, metastases and survival.

Effects of delayed (24 h postintervention) beta-irradiation therapy after coronary angioplasty and stenting in de novo native coronary artery lesions; Results of a randomized clinical and intravascular ultrasound study.

BACKGROUND: The effects of brachytherapy performed 24 h postintervention in de novo native coronary artery lesions. METHODS AND RESULTS: Thirty-nine patients with 39 de novo coronary artery lesions were randomised to prompt (immediately after intervention, n=21) or delayed (24 h later, n=18) beta brachytherapy ((90)Sr/(90)Y) after been successfully revascularized with stenting. Clinical follow-up data up to 21 months (median time) were compared. After irradiation and at 6-month follow-up, paired volumetric analysis of the stented segment and the 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque, and media (external elastic membrane minus lumen), stent and intima hyperplasia (stent minus lumen). Baseline clinical and angiographic characteristics were similar in the two groups. Postintervention measurements of stent, lumen, and intima hyperplasia volumes as well as postintervention minimum lumen cross-sectional areas were not different. In the stented segments and in the segments 5 mm proximal and distal to the stent, similar changes of all IVUS measurements were measured in the two patient groups, but in the lumen volume at the proximal stent edge of patients irradiated 24 h postinjury. At 21 months median follow-up time, target lesion revascularization (TLR) was performed in 8 patients (38%) in the prompt irradiation group compared with 3 (17%) in the delayed (P=.17). CONCLUSION: Beta irradiation is similarly effective whether performed immediately after percutaneous coronary intervention or 24 h later.

External beam irradiation in angioplasted arteries of hypercholesterolemic rabbits. The dose and time effect.

PURPOSE: To study the dose and time effect of external beam irradiation on the morphometry of both angioplasted and nonangioplasted arteries in a hypercholesterolemic rabbit model. METHODS AND MATERIALS: Eight groups of rabbit femoral arteries were studied: arteries (a) with no intervention, (b) irradiated with a 12-Gy 6 MV X-ray dose, (c) with a 18-Gy, (d) treated with balloon angioplasty, (e) dosed with 12-Gy half an hour post-angioplasty, (f) dosed with 18-Gy half an hour post-angioplasty, (g) dosed with 12-Gy 48 h post angioplasty, (g) dosed with 18-Gy 48 h post angioplasty. RESULTS: External irradiation at either 12 or 18 Gy was not found to change vessel morphometry in noninjured arteries. The 12-Gy dose given soon after angioplasty further increased percentage stenosis (63% on the average), despite the preservation of the lumen cross-sectional area. Positive remodeling was not observed in arteries given 18-Gy half an hour post angioplasty to counterbalance the increased neointimal formation. Therefore, this treatment resulted in a drastic reduction in lumen area and in enhancement of percentage stenosis (84% on the average). On the contrary, the delayed irradiation of the angioplasted arteries at either 12 or 18 Gy was not found to influence any of the studied morphometric parameters 5 weeks after angioplasty. CONCLUSIONS: Uniform external beam irradiation up to 18 Gy was well tolerated by intact femoral arteries. Prompt 12- or 18-Gy irradiations accentuated percentage stenosis. However the lumen cross-sectional area was preserved only at the lower dose point. Delayed irradiation at any dose did not influence the restenosis process.

Thermoluminescence dosimetry for quality assurance in radiation therapy.

A methodology based on thermoluminescence dosimetry was developed to check the output of teletherapy units and the given doses. It was applied in a hospital as a part of an extemal quality audit programme. Over a 7 year period the mean ratios of the output doses measured by TLDs calibrated free-in-air to the doses measured at the hospital in a 6 MV X ray and in a 60Co unit were 1.000 +/- 0.024 (n = 86) and 0.997 +/- 0.027 (n=61), respectively. TLDs in capsules were attached to the patient's body or to a phantom to assess entrance, exit and midline doses and transmission. Factors were determined experimentally to relate the doses measured with TLDs in capsules and inside the body. The accuracy in given doses with pelvic and tangential breast fields and assessed via 752 in vivo measurements, was considered to be adequately good, taking into account the limitations of the equipment available in the hospital.