DEGRO guidelines for the radiotherapy of non-malignant disorders. Part II: Painful degenerative skeletal disorders.

BACKGROUND AND PURPOSE: The purpose of this article is to summarize the updated DEGRO consensus S2e guideline recommendations for the treatment of benign painful degenerative skeletal disorders with low-dose radiotherapy. MATERIALS AND METHODS: This overview reports on the role of low-dose radiotherapy in the treatment of enthesiopathies (shoulder syndrome, trochanteric bursitis, plantar fasciitis, and elbow syndrome) and painful arthrosis (knee, hip, hand, and finger joints). The most relevant aspects of the DEGRO S2e Consensus Guideline Radiation Therapy of Benign Diseases 2014 regarding diagnostics, treatment decision, dose prescription as well as performance of radiotherapy and results are summarized. RESULTS: For all indications mentioned above, retrospective and some prospective analyses have shown remarkable effects in terms of pain relief. Nevertheless, the Level of Evidence (LoE) and the Grade of Recommendation (GR) vary: LoE 1b-4 and GR A-C. CONCLUSION: Low-dose radiotherapy for painful degenerative skeletal disorders is effective in the majority of the patients and therefore it may be a reasonable therapeutic alternative when simple and non-invasive methods have been used without persistent success. For all discussed entities, single fraction doses of 0.5-1.0 Gy and total doses of 3.0-6.0 Gy/series applied with 2-3 fractions per week are recommended.

Intensified local treatment and systemic therapy significantly increase survival in patients with brain metastases from advanced breast cancer - a retrospective analysis.

BACKGROUND: Brain metastases have evolved from a rare to a frequently encountered event in advanced breast cancer due to advances in palliative systemic treatment. PATIENTS AND METHODS: All Patients treated at our centre from 1994 to 2004 with WBRT for brain metastases from breast cancer were included. We performed a multivariate analysis (Cox regression) to explore which factors are able to influence significantly cerebral time to progression (TTP) and overall survival (metastatic sites [visceral versus non-visceral], Karnofsky performance score [KPS], age, intensified local treatment [boost irradiation, neuro-surgical resection] further systemic treatment). RESULTS: Overall 174 patients, median age 51 years, range 27-76 years, were included. Median TTP was 3 months (m), range 1-33+ m. Median overall survival was 7 m, range 1-44 m. Factors significantly influencing TTP were KPS (p = 0.002), intensified local treatment (p < 0.001), and palliative systemic treatment (p = 0.001). Factors significantly influencing survival were intensified local treatment (p = 0.004), metastatic sites (p = 0.008), KPS (p = 0.006), and palliative systemic treatment (p < 0.001). CONCLUSION: As shown by the significant influence of metastatic sites, some patients die from their advanced systemic tumour situation before they would die from cerebral progression. In other individuals however, intensified local treatment and systemic treatment appear to influence cerebral time to progression and overall survival.

Ultrasound-guided interstitial brachytherapy in the treatment of advanced vaginal recurrences from cervical and endometrial carcinoma.

BACKGROUND: In advanced vaginal recurrences of cervical and endometrial carcinomas therapeutic options are rare because of preceding therapy. PATIENTS AND METHODS: 23 patients developing advanced vaginal recurrences of cervical and endometrial carcinomas were included. 15 patients started with external-beam therapy to the pelvis and eight patients after preceding radiotherapy underwent brachytherapy alone. All patients had ultrasound-guided implantation of transvaginal or transperineal interstitial needles for brachytherapy. Median prescribed total dose was 64 Gy. RESULTS: 18 patients (78%) achieved complete remission. Six patients are alive without tumor and one with tumor after a median follow-up of 64 months. 14 patients died of tumor and two of intercurrent disease. 5-year disease-specific survival and local control rate were 43% and 47%, respectively, in patients with complete remission. Univariate analysis found time to relapse > 2 years, initial diameter < or = 4 cm, initial volume < 15 cm(3), no extension to the pelvic side wall, volume before brachytherapy < 7.5 cm(3), brachytherapy coverage index > 0.8, and prescribed total dose > 64 Gy being positive predictors for local control and survival. CONCLUSION: The use of ultrasound guidance for placement of interstitial needles in template-based brachytherapy of advanced recurrent gynecologic malignancies is a feasible, safe, and cheap method with encouraging results. Today, ultrasound imaging can be also used to some extent for treatment planning which requires further development. Patient- and treatment-related prognostic factors can be defined.

Pilot study in the treatment of endometrial carcinoma with 3D image-based high-dose-rate brachytherapy using modified Heyman packing: clinical experience and dose-volume histogram analysis.

PURPOSE: The aim of this study was to evaluate dose distribution within uterus (clinical target volume [CTV]) and tumor (gross tumor volume [GTV]) and the resulting clinical outcome based on systematic three-dimensional treatment planning with dose-volume adaptation. Dose-volume assessment and adaptation in organs at risk and its impact on side effects were investigated in parallel. METHODS AND MATERIALS: Sixteen patients with either locally confined endometrial carcinoma (n = 15) or adenocarcinoma of uterus and ovaries after bilateral salpingo-oophorectomy (n = 1) were included. Heyman packing was performed with mean 11 Norman-Simon applicators (3-18). Three-dimensional treatment planning based on computed tomography (n = 29) or magnetic resonance imaging (n = 18) was done in all patients with contouring of CTV, GTV, and organs at risk. Dose-volume adaptation was achieved by dwell location and time variation (intensity modulation). Twelve patients treated with curative intent received five to seven fractions of high-dose-rate brachytherapy (7 Gy per fraction) corresponding to a total dose of 60 Gy (2 Gy per fraction and alpha/beta of 10 Gy) to the CTV. Four patients had additional external beam radiotherapy (range, 10-40 Gy). One patient had salvage brachytherapy and 3 patients were treated with palliative intent. A dose-volume histogram analysis was performed in all patients. On average, 68% of the CTV and 92% of the GTV were encompassed by the 60 Gy reference volume. Median minimum dose to 90% of CTV and GTV (D90) was 35.3 Gy and 74 Gy, respectively. RESULTS: All patients treated with curative intent had complete remission (12/12). After a median follow-up of 47 months, 5 patients are alive without tumor. Seven patients died without tumor from intercurrent disease after median 22 months. The patient with salvage treatment had a second local recurrence after 27 months and died of endometrial carcinoma after 57 months. In patients treated with palliative intent, symptom relief was achieved. No severe acute and late side effects (Grade 3/4) were observed. CONCLUSIONS: Sectional image-based three-dimensional treatment planning on computed tomography and magnetic resonance imaging is feasible in definitive brachytherapy of endometrial carcinoma and enables by the use of dwell time and location adaptation a sufficient coverage of GTV and major parts of CTV. Local control in this limited number of patients is excellent and rate of side effects minimal.

Retrospective analysis of re-irradiation in malignant glioma: a single-center experience.

INTRODUCTION: Malignant gliomas are brain tumors deriving from the brain's glia cells. Primary treatment comprises resection, irradiation and chemotherapy, but these tumors almost always recur. In this situation, palliative chemotherapy is relatively well established, but a second local treatment is sometimes possible. We evaluated the safety and efficacy of re-irradiation in patients with recurrent malignant glioma. PATIENTS AND METHODS: Twenty-two patients were treated with a second irradiation for recurrent or progressive glioma. Patients either received hypo-fractionated stereotactic treatment or conventionally fractionated conformal therapy, depending on tumor size. Wherever possible, a second resection was performed. Time to progression (TTP) and survival were estimated using the Kaplan-Meier product-limit method. RESULTS: Median age was 31 (8-77) years. Median TTP after onset of re-treatment was 4 (1-31) months. Median overall survival was 7 (1-46) months, and overall survival from primary diagnosis was 49 (7-136) months. Significantly longer TTP (P = 0.008) and overall survival (P = 0.005) were observed in re-resected patients than in those without a second surgical intervention. CONCLUSION: Re-irradiation in malignant glioma is a feasible and safe treatment option, and the benefit appears to be especially large in re-resected patients. To make a final conclusion possible, larger prospective trials are warranted.

Oxygenation status of cervical carcinomas before and during spinal anesthesia for application of brachytherapy.

BACKGROUND AND PURPOSE: To date, no information is available concerning the impact of spinal anesthesia on the oxygenation status of carcinomas of the uterine cervix. The aim of this study was therefore to determine the influence of spinal anesthesia on the oxygenation status of cervical carcinomas. PATIENTS AND METHODS: In ten patients with cervical carcinoma who received spinal anesthesia for a first application of brachytherapy, intratumoral pO2 measurements (pO2 histography system, Eppendorf-Netheler-Hinz, Hamburg, Germany) were performed. Systemic parameters were documented prior to and during spinal anesthesia. Patients breathed room air spontaneously. For further evaluation, all intratumoral pO2 values were pooled, and overall median pO2 values and fractions of hypoxic pO2 values < or = 5 mmHg were calculated. Overall median pO2 values in the subcutis were also calculated. RESULTS: There were no significant changes of systemic parameters, median subcutaneous pO2 values, median intratumoral pO2 values, and the fractions of hypoxic pO2 values < or = 5 mmHg in the tumor upon administration of spinal anesthesia. The variability of measured pO2 values increased during spinal anesthesia, although substantial changes in the oxygenation status were only seen in individual cases (n = 2). CONCLUSION: This study shows for the first time that the oxygenation status of cervical carcinomas, in general, is not influenced by spinal anesthesia prior to application of brachytherapy. To conclude, the data presented suggest that reliable pO2 measurements can be performed under spinal anesthesia. At the same time, since no substantial changes in tumor oxygenation were observed, spinal anesthesia should not affect the O2-related efficacy of high-dose-rate brachytherapy.

Surgery and adjuvant radiation therapy of endometrial stromal sarcoma.

OBJECTIVE: In the treatment of endometrial stromal sarcoma, it is still not clear whether adjuvant radiation therapy improves the outcome. We wish to summarize the experiences we gathered from treating 15 patients over a period of 18 years, and to compare these to results from literature. PATIENTS AND METHODS: According to the 1989 FIGO classification for endometrial carcinoma, 11 (73%) of the 15 patients analyzed presented stage I, 1 presented stage II, and 3 presented stage III sarcoma. Of these, 11 patients (73%) had high grade stromal sarcoma and 4 had low grade stromal sarcoma. All patients were treated with surgery and adjuvant radiation therapy. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed on 11 patients (73%), vaginal hysterectomy and bilateral salpingo-oophorectomy on 2 patients, and total abdominal hysterectomy on 2 patients. Combined radiotherapy was performed on 13 patients (93%), while isolated brachytherapy and isolated external beam therapy were each performed on 1 patient. External beam therapy was administrated in daily fractions of 1.6-2.0 Gy up to a total dose of 37-57 Gy to the pelvis. RESULTS: Follow up ranged from 23 to 170 months (mean: 80 mths). 10 patients (67%) are still alive without tumor, and 5 patients have died. Of these, one died due to intercurrent disease, one due to breast-cancer, and 3 due to endometrial stromal sarcoma, presenting distant metastases within one year after therapy. Only one patient presented with an additional local recurrence. The overall actuarial survival and the disease specific survival rate was 72% and 79% respectively after 5 years, and 60% and 79% after 10 years. The overall local control rate was 93% after 5 years. There were no severe acute side effects and no late side effects. CONCLUSION: In our experience, the most effective treatment for patients with endometrial stromal sarcoma is total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant radiation therapy, due to the excellent local monitoring possibilities in all stages of disease, and a good disease specific survival in early stages.