Palliative total skin electron beam therapy (TSEBT) for advanced cutaneous T-cell lymphoma.

Our aim was to analyze the effectiveness of palliative total skin electron beam therapy (TSEBT) in the management of advanced cutaneous T-cell non-Hodgkin's lymphoma (CTCL). Eighteen patients (median age 59 years) with advanced and therapy-refractory CTCL in stages IIB-IV were treated with TSEBT for the first time. The most common histological subtype was Mycosis fungoides (72%). All patients suffered from lymphoma-associated symptoms. Median daily fractions of 1 Gy were administered up to a median total dose of 25 Gy. The median follow-up period was 11 months. Nine patients (50%) achieved a complete response and seven patients (39%) had a limited response. The actuarial one-year progression-free survival was 24%. Four patients (22%) had continuing remission over a median period of six months. Lymphoma associated symptoms were improved in 16 patients (89%). The median overall survival after receiving TSEBT was 12 months, resulting in an actuarial one-year overall survival of 48%. Treatment related acute effects (grade 1 or 2) were observed in all patients during radiation therapy. Transient grade 3 epitheliolyses developed in five patients (28%), late skin effects (grade 1 and 2) in 16 patients (89%), and hypohidrosis was seen in six patients (33%). We conclude that TSEBT is a very efficient and tolerable palliative treatment for patients with advanced CTCL.

Development and psychometric evaluation of the Basic Documentation for Psycho-Oncology, a tool for standardized assessment of cancer patients.

OBJECTIVE: This study describes the development and psychometric evaluation of the Basic Documentation for Psycho-Oncology (PO-Bado), an expert rating scale designed for the comprehensive assessment of psychosocial and physical distress in cancer patients. While there are many self-report measures (usually used for screening purposes), the PO-Bado is the first standardized clinician-administered instrument to guide professionals in a focused and structured psycho-oncological assessment. METHODS: The validation procedure was performed in 596 patients from different settings of cancer care, including all cancer sites and stages of the disease. The psychometric evaluation included (a) determination of the factorial structure, (b) homogeneity of scales and interrater reliability, (c) convergent and discriminant validities, and (d) examination of sensitivity to change. RESULTS: The final version of the PO-Bado includes two scales: the physical distress scale (four items) and the psychological distress scale (eight items). A manual and an interview guideline were developed alongside. The psychometric properties suggest that the PO-Bado is a reliable and valid tool used to assess and to differentiate the distress of patients with cancer, as well as treatment-related changes in distress. CONCLUSION: We suggest that the PO-Bado is a useful tool that is applicable in different oncology settings. It complements self-report measures and provides a structured format for focused psycho-oncological assessment and intervention. The two-dimensional structure allows differentiation between physical and psychological problems, assisting professionals in their diagnostic efforts and in providing appropriate support or treatment. When used consistently across professions and settings, the PO-Bado can form the basis for audit and interdisciplinary communication.

Postoperative electron beam radiotherapy for keloids: objective findings and patient satisfaction in self-assessment.

AIM: To evaluate the role of postoperative radiotherapy in the management of keloids. METHODS: Forty-seven patients with a combined total of 60 keloids were treated with 6-MeV electron beam radiotherapy after surgical excision of the keloids. Mean daily fractions of 4 Gy (range, 3-5 Gy) were administered up to a total dose of 16 Gy (range, 12-18 Gy). The median follow-up was 70 months. Patients were asked to complete a questionnaire addressing their satisfaction with the treatment results. This self-assessment was compared with the clinical outcome. RESULTS: Four keloids (7%) relapsed completely, and five recurrences (8%) were classified as limited relapses. All recurrences were observed at sites of high stretch-tension. Keloid-associated symptoms, e.g. itching and pain, were improved in 81%. Hypopigmentation was observed in 29 patients (62%), a mild redness of the scar in eight patients (17%), and grade 1 telangiectasias in two patients (4%). No severe complications or secondary malignancies were observed. Self-assessments did not fully correspond to the clinical examination and recurrence status. Twelve patients were not satisfied with the treatment result, but only two of these relapsed completely. Three relapsed patients described the result of therapy as excellent or good. CONCLUSION: Postoperative electron radiotherapy is well tolerated and very effective in preventing keloid recurrence. To avoid an overestimation of cosmetic outcome, patients should be informed about achievable results before therapy starts.

Radiotherapy for localised and advanced Merkel cell carcinoma of the skin: a single institution case series.

Merkel cell carcinoma (MCC) is a rare malignant tumour of the skin with a tendency to rapid local progression, frequent spread to regional lymph nodes and distant metastases. We report results with radiotherapy in the treatment of MCC.Thirty-nine patients with histologically proven MCC were treated. Fifteen patients had stage I disease (12 primary, 3 recurrent tumours). Twenty-one patients had stage II disease (10 primary, 11 recurrent tumours). Thirty patients were treated with surgery and adjuvant radiotherapy. Six patients with inoperable disease received radiotherapy alone. Three patients in stage III with distant metastases were treated with palliative radiotherapy. For stage I patients, 3-year loco-regional control (LC), disease-specific survival (DSS) and overall survival (OS) rates were 90%, 100%, and 100%, respectively. For stage II patients, LC, DSS, and OS were 78%, 55%, and 29%, respectively. LC did not differ significantly between stage I and II patients. But, patients presented to radiotherapy directly after operation showed significantly improved LC compared to patients referred in recurrent situation (p = 0.039). Two of six inoperable patients treated with radiotherapy alone relapsed locally. In the current study, surgery and immediate adjuvant radiotherapy resulted in strong loco-regional control. Radiotherapy alone is suggested only in inoperable or metastatic MCC.

Patterns of failure and local control after intraoperative electron boost radiotherapy to the presacral space in combination with total mesorectal excision in patients with locally advanced rectal cancer.

PURPOSE: To evaluate local control and patterns of failure in patients treated with intraoperative electron beam radiotherapy (IOERT) after total mesorectal excision (TME), to appraise the effectiveness of intraoperative target definition. METHODS AND MATERIALS: We analyzed the outcome of 243 patients with rectal cancer treated with IOERT (median dose, 10 Gy) after TME. Eighty-eight patients received neoadjuvant and 122 patients adjuvant external beam radiotherapy (EBRT) (median dose, 41.4 Gy), and in 88% simultaneous chemotherapy was applied. Median follow-up was 59 months. RESULTS: Local failure was observed in 17 patients (7%), resulting in a 5-year local control rate of 92%. Only complete resection and absence of nodal involvement correlated positively with local control. Considering IOERT fields, seven infield recurrences were seen in the presacral space, resulting in a 5-year local control rate of 97%. The remaining local relapses were located as follows: retrovesical/retroprostatic (5), anastomotic site (2), promontorium (1), ileocecal (1), and perineal (1). CONCLUSION: Intraoperative electron beam radiotherapy as part of a multimodal treatment approach including TME is a highly effective regimen to prevent local failure. The presacral space remains the site of highest risk for local failure, but IOERT can decrease the percentage of relapses in this area.

Radiotherapy for orbital lymphoma : outcome and late effects.

PURPOSE: To analyze the effectiveness of radiotherapy in the management of orbital non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: 42 patients (median age 64.5 years) were reviewed retrospectively. The median follow-up period was 58 months. 26 patients had stage IE orbital lymphoma (22 indolent, four aggressive NHLs). 16 patients had advanced NHLs in stages II-IV with orbital involvement (eleven indolent, five aggressive NHLs). The median radiation dose was 40 Gy (20-46 Gy) for indolent lymphoma and 44 Gy (20-48 Gy) for aggressive lymphoma. Patients with stage IE were treated with at least 30 Gy. RESULTS: The 5-year local control rate for patients with stage I was 100%, the 5-year overall survival 91%. Two distant relapses were found, but no lymphoma-related death was detected. The 5-year local control rate for patients in stages II, III, and IV was 80%. Two local failures were detected. The 5-year overall survival for the advanced stages was 47%, nine patients with stages III and IV died due to systemic progression of lymphoma. Acute, radiotherapy-related complications grade 3/4 were not observed. Late effects grade 1/2 were documented in 45%. Six patients, treated with doses of > 36 Gy, developed grade 3 complications (four cataract, two dryness). CONCLUSION: Radiotherapy alone yields excellent local control and overall survival rates in orbital lymphoma stage IE. Local irradiation is also well tolerated and effective in advanced NHL stages with orbital infiltration. Doses of > 36 Gy resulted in an increase of late complications.

[Pain and quality of life following palliative radiotherapy of bone metastases]. / Der Einfluss palliativer Strahlentherapie auf Schmerz und Lebensqualität bei Patienten mit Knochenmetastasen.

BACKGROUND AND PURPOSE: Palliative irradiation is used to provide pain relief and to increase quality of life. Most studies exclude patients with advanced cancer disease and, therefore, a positive selection results. This prospective clinical study investigates the effect of palliative radiotherapy on pain and quality of life of patients with painful bone metastases. PATIENTS AND METHODS: 263 patients with bone metastases due to advanced cancer were observed with respect to pain and quality of life during a 2-month course of radiotherapy. Missing data were substituted by the LOCF method (last observation carried forward) to prevent a biased reduction of data. RESULTS: Radiotherapy resulted in pain relief. In the complete group, pain medication was not increased. Quality of life was not affected positively. Side effects of radiotherapy increased remarkably. CONCLUSION: Radiotherapy leads to pain relief. However, risks and benefits must be considered critically due to side effects.

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer.

BACKGROUND: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

Intraoperative electron-beam therapy for primary and recurrent retroperitoneal soft-tissue sarcoma.

PURPOSE: This study assesses the long-term outcome of patients with retroperitoneal soft-tissue sarcomas treated by maximal resection in combination with intraoperative electron-beam therapy (IOERT) and postoperative external-beam radiotherapy. METHODS AND MATERIALS: From 1991 to 2004, 67 patients were treated with curative intent for primary (n = 26) or recurrent (n = 41) retroperitoneal soft-tissue sarcoma. All patients underwent maximal resection in combination with IOERT (mean dose, 15 Gy), 45 patients underwent additional postoperative EBRT, and 20 patients were previously irradiated. RESULTS: The 5-year actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from metastatic disease of all patients was 64%, 28%, 40%, and 50%, respectively. The 5-year LC inside the IOERT field was 72%. For patients who completed IOERT and EBRT after R0-resection 5-year and 10-year OS was 80%, and 5-year and 10-year LC was 100%. Only 1 of the 21 patients after R0-resection and only 8 of 34 patients after R1-resection compared with 9 of 12 patients after R2-resection experienced inside IOERT-field relapse. Grade II or higher late complications were seen in 21% of the patients, but only 2 patients required surgical intervention because of late complications. CONCLUSION: In selected patients, IOERT results in excellent local control and survival, with acceptable morbidity.

Influence of intraoperative and postoperative radiotherapy on functional outcome in patients undergoing standard and deep anterior resection for rectal cancer.

PURPOSE: This study was designed to investigate the influence of intraoperative and postoperative radiotherapy on functional outcome after rectal resection for rectal cancer. METHODS: One hundred patients who underwent deep or standard anterior resection for rectal cancer were included in this follow-up study. All patients filled out questionnaires regarding morbidity and functional outcome; a subgroup (n = 63) underwent further clinical evaluation. The results were stratified according to radiation: Group I, no radiation (n = 37); Group II, only intraoperative radiation (n = 12); Group III, intraoperative and postoperative radiation (n = 51). RESULTS: Anal continence measured by Kirwan-Parks classification and Wexner score was significantly different within the three groups (P < 0.005, P < 0.0001), whereas continence impairment was least in Group I and greatest in Group III. Patients in Group III demonstrated a significantly worsecategory in the Kirwan-Parks classification and worse Wexner scores compared with patients in Group I (P < 0.0001). Patients only having undergone intraoperative radiotherapy had a significantly worse continence (Kirwan-Parks classification) than patients without any radiotherapy (P < 0.05). More patients after intraoperative and postoperative radiation therapy complained of fragmented stools (P < 0.05) and urgency (P < 0.05) compared with patients only having undergone surgery; the need to wear pads was higher (P = 0.001). Vector volume manometry revealed better resting sphincter function in Group I compared with Group III (P < or = 0.005). CONCLUSIONS: Patients with anterior resection for rectal cancer who undergo full-dose radiotherapy have significantly more impairment of anorectal function than patients without radiotherapy. Patients who were only exposed to intraoperative radiotherapy showed moderate impairment of continence function, suggesting that the influence of radiotherapy on anal function may be dose-dependent and application-dependent.

Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma.

PURPOSE: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 153 patients who were treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. RESULTS: Five-year overall survival and 5-year local control rates were 77% and 78%, respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2-4 was observed in 23% and late toxicity Grade 2-4 in 17% of patients. CONCLUSIONS: Treatment with IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma.

Combination of external-beam radiotherapy with intraoperative electron-beam therapy is effective in incompletely resected pediatric malignancies.

PURPOSE: Intraoperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. METHODS AND MATERIALS: The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. RESULTS: After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In 1 child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. CONCLUSIONS: Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients.

Frameless image guidance improves accuracy in three-dimensional interstitial brachytherapy needle placement.

PURPOSE: The aim of this work was to adapt a computer-assisted real-time three-dimensional (3D) navigation system for interstitial brachytherapy procedures. METHODS AND MATERIALS: The 3-D navigation system Surgical Planning and Orientation Computer System (SPOCS; Aesculap, Tuttlingen, Germany) was adapted for use in interstitial brachytherapy. A special needle holder with mounted infrared-emitting diodes (IRED) for 3D navigation-based needle implantation was developed. Measurements were made on a series of different phantoms to study the feasibility and the overall accuracy and precision of the navigation system with regard to single-needle application and volume implants (multiple-needle implantations). In all, 250 single implants and 20 volume implants were performed. Accuracy was measured as the target registration error (TRE) between the preoperatively defined and the achieved target position. RESULTS: Analyses of the 250 different targets showed a mean TRE for single-needle applications of 1.1 mm (SD +/- 0.4 mm), 0.9 mm (SD +/- 0.3 mm), and 0.7 mm (SD +/- 0.3 mm) in the x, y, and z direction, respectively. The maximal deviation was 2.3 mm. The corresponding TRE in the x, y, and z direction for volume implants was 1.6 mm (SD +/- 0.4 mm), 1.9 mm (SD +/- 0.6 mm), and 1.0 mm (SD +/- 0.4 mm), respectively. The maximum deviation was 2.9 mm. CONCLUSIONS: The adaptation of a commercially available surgical planning and navigation system to interstitial brachytherapy is feasible. It enables virtual planning and improved accuracy in 3D interstitial needle implantation.

Decreased detection rate of disseminated tumor cells of rectal cancer patients after preoperative chemoradiation: a first step towards a molecular surrogate marker for neoadjuvant treatment in colorectal cancer.

OBJECTIVE: To compare the detection rates for rectal cancer cells in blood and bone marrow in patients with or without preoperative chemoradiation. SUMMARY BACKGROUND DATA: Previous reports have postulated a resistance of disseminated tumor cells to antiproliferative agents because of tumor cell dormancy. METHODS: Blood samples from 142 patients (pre, intra-, and postoperative samples) and bone marrow samples from 127 patients undergoing resection of rectal adenocarcinoma were analyzed for tumor cells using a cytokeratin (CK) 20-reverse transcription polymerase chain reaction. The results were stratified according to preoperative therapy. RESULTS: In patients without preoperative chemoradiation, tumor cell detection in blood and bone marrow correlated to tumor stage (Cochran Armitage trend test, P < 0.05). Tumor cells were detected in 34 of 103 (33%) bone marrow and 65 of 117 (55.6%) blood samples of patients without neoadjuvant treatment versus in 4 of 24 (16.7%) bone marrow and in 10 of 25 (40%) blood samples of patients with neoadjuvant treatment. The tumor cell detection rate was significantly lower in the group having undergone chemoradiation (binary logistic regression analysis, P < 0.05). The overall and disease-free survival were significantly worse in patients with tumor cell detection in the bone marrow after neoadjuvant therapy. CONCLUSIONS: Preoperative chemoradiation is associated with a decreased detection rate of rectal cancer cells in blood and bone marrow. These findings may explain the observed clinical benefit of patients with rectal cancer receiving chemoradiation. This is the first study suggesting that detection of disseminated rectal cancer cells may be useful for assessing the efficacy of neoadjuvant therapy.

Combination of early bisphosphonate administration and irradiation leads to improved remineralization and restabilization of osteolytic bone metastases in an animal tumor model.

BACKGROUND: The goal of the current study was to analyze the combined effect of bisphosphonates (BPs) and irradiation on remineralization and restabilization of osteolytic bone metastases in an animal tumor model. METHODS: Bone metastases were induced in male Wistar rats via intraosseous injection of the Walker carcinosarcoma 256B cell line into both proximal tibia metaphyses on Day 1 of the study. Three treatment groups were analyzed. All animals received a single radiation dose of 17 grays (in the form of 6-megaelectron-volt electrons) on Day 7 and were sacrificed on Day 49. Group 1 (the control group) was treated with irradiation only. Groups 2 and 3 received additional BPs (clodronate; daily intraperitoneal injection dose, 20 mg/kg per day). In Group 2, BPs were given before irradiation, on Days 3-6; this schedule later was referred to as early BP treatment. In Group 3, BPs were administered simultaneously with irradiation, on Days 7-10; this schedule later was referred to as simultaneous BP treatment. The endpoints of the study were bone density and microstructural parameters of bone on Day 49. Bone density was measured using X-ray absorption. Microstructural parameters of bone were assessed using histomorphometry. A total of thirty tibiae were analyzed in each group. RESULTS: After irradiation, bone density was significantly higher among animals in the early BP treatment group compared with those in the control group and those in the simultaneous BP treatment group (P = 0.001). Histomorphometric analysis of bone showed significantly better-preserved (P < 0.001) microstructural parameters (bone area, trabecular number, and trabecular separation) in the early BP treatment group compared with the control and simultaneous BP treatment groups. CONCLUSIONS: Early BP administration in combination with irradiation led to improved remineralization and restabilization of osteolytic bone metastases in an animal tumor model.

Open low-field magnetic resonance imaging in radiation therapy treatment planning.

PURPOSE: To evaluate the possibilities of an open low-field magnetic resonance imaging (MRI) scanner in external beam radiotherapy treatment (RT) planning. METHODS AND MATERIALS: A custom-made flat tabletop was constructed for the open MR, which was compatible with standard therapy positioning devices. To assess and correct image distortion in low-field MRI, a custom-made phantom was constructed and a software algorithm was developed. A total of 243 patients (43 patients with non-small-cell lung cancer, 155 patients with prostate cancer, and 45 patients with brain tumors) received low-field MR imaging in addition to computed tomographic (CT) planning imaging between January 1998 and September 2001 before the start of the irradiation. RESULTS: Open low-field MRI provided adequate images for RT planning in nearly 95% of the examined patients. The mean and the maximal distortions 15 cm around the isocenter were reduced from 2.5 mm to 0.9 mm and from 6.1 mm to 2.1 mm respectively. The MRI-assisted planning led to better discrimination of tumor extent in two-thirds of the patients and to an optimization in lung cancer RT planning in one-third of the patients. In prostate cancer planning, low-field MRI resulted in significant reduction (40%) of organ volume and clinical target volume (CTV) compared with CT and to a reduction of the mean percentage of rectal dose of 15%. In brain tumors, low-field MR image quality was superior compared with CT in 39/45 patients for planning purposes. CONCLUSIONS: The data presented here show that low-field MRI is feasible in RT treatment planning when image correction regarding system-induced distortions is performed and by selecting MR imaging protocol parameters with the emphasis on adequate images for RT planning.

Integration of intraoperative radiotherapy (IORT) dose distribution into the postoperative CT-based external beam radiotherapy (EBRT) treatment planing.

In the treatment of malignant disease external beam radiation therapy (EBRT) is often combined with surgery. Intraoperative radiotherapy (IORT) improves the local control by dose escalation. For reasons of recording, improvement and security of the intervention, it would be necessary to merge the IORT-dose distribution with the postoperative CT-based EBRT-planing. The aim of this work was to develop a method to reconstruct the IORT field and register it with the postoperative planing CT. This enables the reconstruction of the IORT dose distribution and merge it with the CT-based EBRT planing data. We use a surface scanner to receive a large amount of surface points which enables us reconstruct the IORT-field and to register it with the CT-based EBRT planning data. Scanning and calculation time is not over 2 seconds, depending mainly on the CPU power. The error of a single point is below 1 mm. The density of the point cloud is approx. 4 per mm2. In this paper we give an overview of our experimental setup and the accuracy of the method.