Lutz Moser

Proton Beam Therapy of Parapapillary Choroidal Melanoma

PURPOSE To analyze the functional outcome with regard to the development of visual acuity and radiation-induced optic neuropathy of patients with parapapillary choroidal melanoma treated with proton beam therapy. DESIGN Clinical case series, retrospective study. METHODS We evaluated 147 consecutive patients with parapapillary choroidal melanoma who received proton beam therapy as primary tumor treatment at the Helmholtz Center in Berlin from 1998 to 2005. A cumulative dose of 60 Cobalt Gray Equivalents (CGE) was delivered to the tumor and the optic disc received a minimum of 50 CGE. Kaplan-Meier analysis was used to assess ocular outcome and survival rates. For trend analysis of functional development, Wilcoxon-Mann-Whitney U test was used to compare the medians of 2 groups and Kruskal-Wallis test was used in the case of more than 2 groups. RESULTS The mean follow-up time was 6.5 years (range 0.3-11.7 years). The most common side effects were radiation-induced optic neuropathy, retinopathy, and cataract. The median visual acuity before and within the first year after therapy was 0.4 logMAR (20/50), lapsing to 1.3 logMAR (20/400) after 3 years and 1.4 logMAR (20/500) after 5 years. During follow-up, no light perception developed in 17 cases (11.6%), mostly attributed to radiation-induced retinopathy, optic neuropathy, and secondary glaucoma. Enucleation was carried out in 14 patients (9.5%) because of local recurrence or severe side effects. CONCLUSION Radiation-induced optic neuropathy is an expected issue after proton beam therapy of parapapillary choroidal melanoma, and visual impairment is common during long-term follow-up, but some useful vision can be preserved in a considerable number of patients.

Adjuvant and neoadjuvant chemoradiation or radiotherapy in rectal cancer—a review focusing on open questions

BackgroundThe therapy of rectal cancer has been a matter of debate since decades, especially with regard to the benefits of neoadjuvant or adjuvant therapies. Principles of additional therapies have been established nearly two decades ago and are questioned nowadays on the basis of more recently modified operative techniques. Benefits and sequelae of therapies have to be balanced against each other, and it seems somewhat likely that a more differentiated strategy than simply stating that every patient with stage II and III rectal cancer needs chemoradiation or radiotherapy will, in long term, be recommended.ConclusionIt should be kept in mind that results of centers of excellence and of phase-III studies with their positively selected patient populations are not representative for all the patients with rectal cancer and physicians treating them.

Salvage proton beam therapy in local recurrent uveal melanoma.

PURPOSE To evaluate survival and ocular outcome in recurrent uveal melanoma treated with proton beam therapy as salvage therapy. DESIGN Retrospective, interventional case series. METHODS We evaluated 48 patients with local recurrence of uveal melanoma after primary treatment with brachytherapy, transpupillary thermotherapy, proton beam therapy, laser photocoagulation, CyberKnife radiation, or photodynamic therapy. All patients received proton beam therapy as a salvage therapy at the Helmholtz Zentrum Berlin between July 2000 and December 2010. Kaplan-Meier analysis was used to obtain survival rates. RESULTS The Kaplan-Meier estimator for local tumor control was 92.1% at 10 years after secondary treatment with proton beam therapy. Local recurrence developed in 3 patients; 1 of them underwent enucleation. During follow-up, 20.8% of the patients died (16.7% of metastasis, 4.1% of other causes or not specified). The most frequent surgical interventions were phacoemulsification (20.8%) and pars plana vitrectomy (10.4%). The Kaplan-Meier estimators were 77.4% for survival and 70.1% for the absence of metastasis 10 years after the primary treatment. CONCLUSIONS Proton beam therapy as a salvage treatment resulted in high local tumor control rates in recurrent uveal melanoma, especially if the primary therapy was transpupillary thermotherapy or plaque brachytherapy. Preservation of the globe was possible in most patients. Enucleations were indicated only in case of re-recurrences of uveal melanoma, but not because of secondary complications like intractable pain or secondary glaucoma. Retreatment was associated with vision deterioration, but loss of vision remained exceptional. Further larger prospective studies are needed to confirm the presented results of our retrospective analysis.

Hormone-Refractory and Metastatic Prostate Cancer – Palliative Radiotherapy

Prostate cancer progression is commonly manifested by obstructive uropathy, regional lymphatic metastases and hematogenous metastases to the axial skeleton. Radiotherapy is a mainstay in the palliation of symptomatic metastatic prostate cancer and is most often used for the palliation of painful metastatic bone lesions, resulting in a relief of pain in about 80-90% of patients and a reduction of analgesics. In metastatic disease compromising the integrity of the spinal cord or a nerve root, radiotherapy can be used as an urgent intervention to minimize neurological dysfunction and local progression or as an adjunct to surgical decompression. Local progression is often associated with hematuria, ureteric obstruction and perineal discomfort. Symptoms of metastatic lymphadenopathy like leg edema and back discomfort caused by pelvic or paraaortic metastases are related to the immediate anatomic structures affected. Radiotherapy for localized hormone-refractory prostate cancer has an excellent local control rate; nevertheless, the prognosis is poor, the majority of patients failing with distant metastasis within few years. The role of radiotherapy in hormone-refractory and metastatic prostate cancer, considering the patients individual situation, are presented and discussed.

Neoadjuvant proton beam irradiation followed by transscleral resection of uveal melanoma in 106 cases

Aims To describe results after neoadjuvant proton beam irradiation followed by transscleral resection of large uveal melanoma. Methods Retrospective interventional case series, including 106 consecutive patients. Local tumour control, enucleation and metastasis development were assessed with survival curves. Predictors of local recurrence and metastasis were investigated with log-rank testing. Results Mean follow-up was 3.2 years. Local recurrence occurred in five cases with an estimated risk of 4.2% and 10.4% at 3 and 5 years after treatment, respectively. Enucleation was performed in 10 cases with an estimated risk of 9.2% and 18.4% at 3 and 5 years, respectively. Significant risk factors for local recurrence were not evident. Metastasis was estimated to occur in 28.4% at 3 years and 40.3% at 5 years, correlating with patients age only (p=0.01). Seventy four patients (69.8%) underwent vitreoretinal surgery for complications after tumour resection. Median visual acuity (VA) was 20/50 at diagnosis and 20/400 in the third year after treatment. VA preservation of 20/200 or better was achieved in 33 patients (31.1%). Conclusion Neoadjuvant proton beam irradiation may help to prevent local recurrence after transscleral resection. Additional vitreoretinal surgery was frequently needed in the presented series. The majority of patients avoided enucleation and functional blindness.

Long-term results after proton beam therapy for retinal papillary capillary hemangioma.

PURPOSE To evaluate the potential benefit and risk of proton beam therapy in the treatment of symptomatic retinal papillary capillary hemangioma. DESIGN Retrospective interventional case series. METHODS This study included patients presenting with symptomatic exudative retinal papillary capillary hemangioma with or without association with von Hippel-Lindau disease. All patients were treated either as a first or a secondary treatment option by proton beam therapy between 2001 and 2009. The minimum follow-up was 30 months. RESULTS Eight eyes of 8 patients (3 male and 5 female, with a mean age of 36 years [range 22-80 years]) were treated for symptomatic papillary retinal hemangioma. The median interval between onset of macular edema and proton beam therapy was 1.7 months (range 0.5-3.3 months). The median follow-up period was 84 months (range 32-106 months) between proton beam treatment and last follow-up. Exudation completely resolved in all but 1 patient after 4.2 months on average (range 2.8-7.2 months). Mean visual acuity prior to proton beam irradiation was 0.7 logMAR (0.2 DIN (DIN 58220 norm)) (range 2-0.3 logMAR) and declined to 0.8 logMAR (0.16 DIN; range 2-0.1 logMAR) at last follow-up examination (no statistical significance, P=.071). CONCLUSION The anatomic outcome after proton beam therapy for retinal papillary hemangioma is convincing, whereas functional outcome may be compromised because of tumor location, long-persisting macular edema, extensive exudation, and poor initial visual acuity. In patients with extended retinal detachment surgical intervention was still necessary. Although proton beam therapy is proven to be a therapeutic option, treatment will remain challenging.

Diagnostik und Therapie choroidaler Melanome

BACKGROUND Prognosis evaluation of patients with choroidal and ciliary melanoma has experienced recent progress through tumour sampling and cytogenetic analysis of metastatic risk. By allocating tumor extension, height and linear basal diameter to defined TNM stages, an estimation of prognosis can also be made without invasive tissue sampling. METHODS Therapeutic strategies of organ preserving irradiation using different sources have clearly come to the forefront. RESULTS Due to microscopic haematogenous spreading of tumour cells prior to treatment, the metastatic risk following radiation of any form is not influenced in comparison to primary enucleation. CONCLUSION However, metastatic disease still remains a fatal condition which currently may only be influenced by early detection and treatment of uveal melanomas.

Histopathological regression grading matches excellently with local and regional spread after neoadjuvant therapy of rectal cancer.

Histopathological regression grading has been shown to predict outcome in chemoradiated rectal cancer. Lymph node spread is still considered the most important single prognostic parameter. Therefore, we investigated the association of regression grading with tumor spread in a single center retrospective cohort. 102 consecutive patients who had undergone neoadjuvant therapy for rectal adenocarcinoma were included. Surgery was performed, including total mesorectal excision. Pathological examination included UICC staging and Dworaks five-tier tumor regression grading. Histological complete response was achieved in 16.7% of cases. Dworaks regression grading and a simplified two tier scheme both correlated excellently with ypT, ypN and UICC stage. However, cases with poor histological response were strongly represented in ypN0. Tumor regression grading is a reliable method for assessment of response to neoadjuvant therapy, but the optimal cut-off for separating good and poor response remains to be established based on clinical outcome.

Proton Beam Therapy Leads to Excellent Local Control Rates in Choroidal Melanoma in the Intermediate Fundus Zone

PURPOSE To evaluate long-term outcomes of proton beam radiotherapy in the treatment of choroidal melanoma of the intermediate zone of the fundus. DESIGN Retrospective interventional single-center study. METHODS The study was a retrospective analysis with long-term follow-up of 62 patients with a minimum tumor-to-disc and tumor-to-fovea distance of 2 mm of choroidal melanoma in the intermediate zone of the fundus. Mean values of tumor prominence, largest basal diameter, and tumor distances to the optic disc and fovea were 7.6, 12.8, 5.2, and 4.6 mm, respectively. All patients were irradiated with a total proton dose of 60 cobalt gray equivalents. RESULTS After proton beam radiotherapy, 71.0% of the patients received subsequent endoresection of the tumor. Only 18 patients (29.0%) did not require additional tumor resection and were analyzed as a separate group. For the total of patients, the median follow-up time was 70.3 months. The 5-year Kaplan-Meier rates of local tumor relapse, enucleation, and distant metastasis were 3.9%, 3.7%, and 13.4%, respectively. Cataract surgery was the most frequent secondary treatment in our cohort. CONCLUSIONS In this study we demonstrate the effectiveness of proton beam irradiation in tumor control and preservation of the globe in the analyzed patients. The rate of metastasis was not higher than previously described. Nevertheless, consecutive tumor surgery is frequently required to maintain the eye in patients with large-sized choroidal melanomas. In conclusion, proton beam radiotherapy allows preservation of the eye in mid-zone choroidal melanomas.

Virtual Simulation of a Boost Field in Adjuvant Radiotherapy of the Breast

Background and Purpose:In CT-based adjuvant radiotherapy of the breast, virtual simulation techniques have been developed. This paper demonstrates a simple virtual simulation of a boost field.Material and Methods:41 fields were planned virtually, 26 as electron beams, 15 as tangential photon beams.Results:Depending on the user’s expertise the geometric accuracy was high; possible sources of error are illustrated. Resulting field sizes tended to be slightly larger compared to conventional simulation when applying the same rules of field definition. Differences in focus-skin distances with consecutive divergence effects as well as partial volume effects were discussed to be causal.Conclusion:Virtual simulation of a boost field has the potential to elegantly link the simplicity of a conventional simulation with the accurate tumor bed identification provided by a CT data set. It was shown to be feasible and favorable with regard to the patient, the medical staff, and the simulator time. Moreover, it offers a visualization of dose distributions, which was found helpful in some cases.Hintergrund und Ziel:Für die CT-geplante adjuvante Strahlentherapie der Brust sind Techniken der virtuellen Simulation entwickelt worden. In dieser Arbeit wird eine einfache virtuelle Simulation eines Boostfeldes demonstriert.Material und Methodik:41 Felder wurden virtuell geplant, 26 als Elektronenfelder, 15 als tangentiale Photonenfelder (Abbildung 1).Ergebnisse:Für erfahrene Anwender war die geometrische Genauigkeit hoch; mögliche Fehlerquellen werden illustriert. Tendenziell waren die resultierenden Felder etwas größer als bei konventioneller Simulation, wenn die gleichen Felddefinitionsregeln angewandt wurden (Tabelle 1). Differierende Fokus-Haut-Abstände mit konsekutiven Divergenzeffekten und Teilvolumeneffekte waren als ursächlich zu diskutieren.Schlussfolgerung:Die virtuelle Simulation eines Boostfeldes hat das Potential, die einfache Technik einer konventionellen Simulation mit der Genauigkeit der Tumorbettidentifizierung im CT-Datensatz elegant zu verbinden. Sie erwies sich als einfach zu handhaben und zeitsparend für die Patientin, das beteiligte medizinische Personal sowie die Simulatornutzung (Tabelle 2). Darüber hinaus ermöglichte sie eine Visualisierung der Dosisverteilung, die in einigen Fällen als hilfreich empfunden wurde (Abbildung 2).