Falk Roeder

Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases

BACKGROUND The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). PATIENTS AND METHODS A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo)radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied. RESULTS Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC. CONCLUSIONS Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Highly effective treatment of skull base chordoma with carbon ion irradiation using a raster scan technique in 155 patients: first long-term results.

The current study was conducted to evaluate the long‐term results of irradiation with carbon ions in a raster scanning technique in patients with skull base chordomas.

IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent head and neck cancer.

AbstractPurpose:In this retrospective investigation, the outcome and toxicity after reirradiation with concurrent cetuximab immunotherapy of recurrent head and neck cancer (HNC) in patients who had contraindications to platinum-based chemotherapy were analyzed.Materials and Methods:Ten patients with locally advanced recurrent HNC were retrospectively evaluated. In 9 cases, histology was squamous cell carcinoma, in one case adenoid cystic carcinoma. External beam radiotherapy was part of the initial treatment in all cases. Reirradiation was carried out using step-and-shoot intensity-modulated radiotherapy (IMRT) with a median dose of 50.4 Gy. Cetuximab was applied as loading dose (400 mg/m2) 1 week prior to reirradiation and then weekly concurrently with radiotherapy (250 mg/m2).Results:The median overall survival time after initiation of reirradiation was 7 months; the 1-year overall survival (OS) rate was 40%. Local failure was found in 3 patients, resulting in a 1-year local control (LC) rate of 61%. The 1-year locoregional control (LRC) rate was 44%, while the 1-year distant metastasis-free survival (DMFS) was 75%. Acute hematological toxicity was not observed in the group. Severe acute toxicity included one fatal infield arterial bleeding and one flap necrosis. Severe late toxicities were noted in 2 patients: fibrosis of the temporomandibular joint in 1 patient and stenosis of the cervical esophagus in another.Conclusions:IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent HNC is feasible with acceptable acute toxicity. Further investigations are necessary to determine the clinical role of this therapy concept.ZusammenfassungZiel:In dieser Untersuchung analysierten wir Behandlungsergebnis und Toxizität nach kombinierter Re-Bestrahlung mit simultaner Cetuximab-Immuntherapie von rezidivierten HNO-Tumoren bei Patienten mit Kontraindikation gegen platinhaltige Chemotherapie.Patientengut und Methode:10 Patienten mit lokal fortgeschrittenen rezidivierten HNO-Tumoren wurden retrospektiv ausgewertet. In 9 Fällen lag histologisch ein Plattenepithelkarzinom, in einem Fall ein adenoidzystisches Karzinom vor. In jedem Fall war eine Strahlentherapie Teil des initialen Behandlungskonzeptes. Die Re-Bestrahlung wurde mittels Step-and-shoot-IMRT mit einer medianen Dosis von 50,4 Gy durchgeführt. Cetuximab wurde als „Loading Dose“ (400 mg/m2) eine Woche vor Re-Bestrahlung und danach wöchentlich simultan zur Bestrahlung (250 mg/m2) verabreicht.Ergebnisse:Das mediane Gesamtüberleben nach Re-Bestrahlung war 7 Monate; das 1-Jahres-Gesamtüberleben betrug 40%. Ein Lokalrezidiv trat bei 3 Patienten auf, was zu einer 1-Jahres-Lokalkontrolle von 61% führte. Die 1-Jahres-lokoregionäre Kontrolle betrug 44%. Das 1-Jahres-Metastasen-freie Überleben war 75% (siehe Abbildungen 1–4). Eine akute hämatologische Toxizität wurde in diesem Kollektiv nicht gesehen. Schwere Akuttoxizitäten waren eine fatale arterielle Blutung und eine Flap-Nekrose. Als schwere Spättoxizität trat eine Fibrose der Pterygiodmuskulatur bzw. des Kiefergelenks sowie eine zervikale Ösophagusstenose auf (vgl. Tabellen 2 u. 3).Schlussfolgerungen:Bei rezidivierten HNO-Tumoren ist eine IMRT-Re-Bestrahlung mit 50 Gy und simultaner Cetuximab- Immuntherapie mit einer akzeptablen Toxizität durchführbar. Es sind weitere Untersuchungen nötig, um den Stellenwert dieser Therapieform zu überprüfen.

Clinical Phase I/II trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis

BackgroundLocal control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered.Methods/designThe trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy) followed by surgery and IORT (10–12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population.DiscussionThe present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity.Trial registrationNCT01566123

Intensity modulated radiotherapy (IMRT) in benign giant cell tumors – a single institution case series and a short review of the literature

BackgroundGiant cell tumors are rare neoplasms, representing less than 5% of all bone tumors. The vast majority of giant cell tumors occurs in extremity sites and is treated by surgery alone. However, a small percentage occurs in pelvis, spine or skull bones, where complete resection is challenging. Radiation therapy seems to be an option in these patients, despite the lack of a generally accepted dose or fractionation concept. Here we present a series of five cases treated with high dose IMRT.Patients and MethodsFrom 2000 and 2006 a total of five patients with histologically proven benign giant cell tumors have been treated with IMRT in our institution. Two patients were male, three female, and median age was 30 years (range 20 -- 60). The tumor was located in the sacral region in four and in the sphenoid sinus in one patient. All patients had measurable gross disease prior to radiotherapy with a median size of 9 cm. All patients were treated with IMRT to a median total dose of 64 Gy (range 57.6 Gy to 66 Gy) in conventional fractionation.ResultsMedian follow up was 46 months ranging from 30 to 107 months. Overall survival was 100%. One patient developed local disease progression three months after radiotherapy and needed extensive surgical salvage. The remaining four patients have been locally controlled, resulting in a local control rate of 80%. We found no substantial tumor shrinkage after radiotherapy but in two patients morphological signs of extensive tumor necrosis were present on MRI scans. Decline of pain and/or neurological symptoms were seen in all four locally controlled patients. The patient who needed surgical salvage showed markedly reduced pain but developed functional deficits of bladder, rectum and lower extremity due to surgery. No severe acute or late toxicities attributable to radiation therapy were observed so far.ConclusionIMRT is a feasible option in giant cells tumors not amendable to complete surgical removal. In our case series local control was achieved in four out of five patients with marked symptom relief in the majority of cases. No severe toxicity was observed.

Correlation of Patient-Related Factors and Dose- Volume Histogram Parameters with the Onset of Radiation Pneumonitis in Patients with Small Cell Lung Cancer

Purpose:To analyze the association of patient- and treatment-related factors with the onset of radiation pneumonitis in a homogeneously treated cohort of patients suffering from small cell lung cancer (SCLC).Patients and Methods:242 patients with SCLC staged as limited disease, who had been treated with chemotherapy and three-dimensional conformal radiotherapy, were retrospectively analyzed. Pneumonitis was defined by typical symptoms and radiographic findings and judged clinically relevant, if drug administration and hospitalization were necessary. Patient- (age, gender, smoking history, performance status, tumor localization, benign lung disease) and treatment-related parameters (V10–V40, mean lung dose [MLD]) were analyzed using χ2-tests for categorical parameters and logistic regression for continuous variables.Results:33 patients (13.6%) developed a clinically relevant pneumonitis, of whom three patients died. All cases of pneumonitis developed within 120 days. None of the patient-related parameters correlated significantly with the onset of pneumonitis. Considering treatment-related parameters, a significant correlation of V30 in regard to total lung and V40 in regard to ipsilateral, contralateral and total lung to the risk of pneumonitis was found. So, the estimated risk of a clinically relevant pneumonitis increased from 10% given a V30 of 13% to 30% given a V30 of 35%. In contrast, no significant correlation was found for V10 and V20 and only a trend for MLD.Conclusion:In this series, high-dose radiation volume parameters, i.e., V30 and especially V40, were identified as the most important factors for the development of radiation pneumonitis. Low-dose radiation volume parameters and clinical parameters played an inferior role in predicting the pneumonitis risk.ZusammenfassungZiel:Überprüfung der Assoziation von patienten- und therapiebezogenen Faktoren mit dem Auftreten einer radiogenen Pneumonitis in einem homogen behandelten Patientenkollektiv mit kleinzelligem Bronchialkarzinom (SCLC).Patienten und Methodik:242 Patienten mit SCLC im Stadium „limited disease“, welche mittels Chemotherapie und dreidimensionaler konformaler Radiotherapie behandelt waren, wurden retrospektiv analysiert. Pneumonitis wurde durch das Auftreten typischer Symptome und radiologischer Befunde definiert und als klinisch relevant eingestuft, wenn medikamentöse Behandlung und Klinikeinweisung nötig waren. Patienten- (Alter, Geschlecht, Rauchanamnese, Allgemeinzustand, Tumorlokalisation, gutartige Lungenerkrankung) und behandlungsbezogene Parameter (V10–V40, mittlere Lungendosis [MLD]) wurden mittels χ2-Tests für kategoriale Parameter und logistischer Regression für kontinuierliche Parameter analysiert.Ergebnisse:33 Patienten (13,6%) entwickelten eine klinisch relevante Pneumonitis, drei Patienten starben. Alle Pneumonitisfälle traten innerhalb von 120 Tagen auf. Für keinen der patientenbezogenen Parameter fand sich eine signifikante Korrelation mit dem Auftreten einer Pneumonitis. Hinsichtlich der behandlungsbezogenen Parameter zeigte sich eine signifikante Korrelation der V30 (gesamte Lunge) sowie der V40 (ipsilaterale, kontralaterale oder gesamte Lunge) mit dem Pneumonitisrisiko. So erhöhte sich das geschätzte Risiko einer klinisch relevanten Pneumonitis von 10% bei einer V30 von 13% auf 30% bei einer V30 von 35%. Im Gegensatz hierzu fanden sich keine signifikanten Korrelationen für V10 und V20 und nur ein Trend für die MLD.Schlussfolgerung:Hochdosis-Volumen-Parameter, d.h. V30 und besonders V40, konnten in dieser Serie als wichtigste Faktoren bezüglich der Entwicklung einer radiogenen Pneumonitis identifiziert werden. Niedrigdosis-Volumen-Parameter und klinische Parameter spielten eine untergeordnete Rolle bei der Vorhersage des Pneumonitisrisikos.

Intraoperative Electron Radiation Therapy (IOERT) in the management of locally recurrent rectal cancer

BackgroundTo evaluate disease control, overall survival and prognostic factors in patients with locally recurrent rectal cancer after IOERT-containing multimodal therapy.MethodsBetween 1991 and 2006, 97 patients with locally recurrent rectal cancer have been treated with surgery and IOERT. IOERT was preceded or followed by external beam radiation therapy (EBRT) in 54 previously untreated patients (median dose 41.4 Gy) usually combined with 5-Fluouracil-based chemotherapy (89%). IOERT was delivered via cylindric cones with doses of 10–20 Gy. Adjuvant CHT was given only in a minority of patients (34%). Median follow-up was 51 months.ResultsMargin status was R0 in 37%, R1 in 33% and R2 in 30% of the patients. Neoadjuvant EBRT resulted in significantly increased rates of free margins (52% vs. 24%). Median overall survival was 39 months. Estimated 5-year rates for central control (inside the IOERT area), local control (inside the pelvis), distant control and overall survival were 54%, 41%, 40% and 30%. Resection margin was the strongest prognostic factor for overall survival (3-year OS of 80% (R0), 37% (R1), 35% (R2)) and LC (3-year LC 82% (R0), 41% (R1), 18% (R2)) in the multivariate model. OS was further significantly affected by clinical stage at first diagnosis and achievement of local control after treatment in the univariate model. Distant failures were found in 46 patients, predominantly in the lung. 90-day postoperative mortality was 3.1%.ConclusionLong term OS and LC can be achieved in a substantial proportion of patients with recurrent rectal cancer using a multimodality IOERT-containing approach, especially in case of clear margins. LC and OS remain limited in patients with incomplete resection. Preoperative re-irradiation and adjuvant chemotherapy may be considered to improve outcome.

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-Hodgkins 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.

Intensity modulated or fractionated stereotactic reirradiation in patients with recurrent nasopharyngeal cancer

PurposeTo report our experience with intensity-modulated or stereotactic reirradiation in patients suffering from recurrent nasopharyngeal carcinomaPatients and MethodsThe records of 17 patients with recurrent nasopharygeal carcinoma treated by intensity-modulated (n = 14) or stereotactic (n = 3) reirradiation in our institution were reviewed. Median age was 53 years and most patients (n = 14) were male. The majority of tumors showed undifferentiated histology (n = 14) and infiltration of intracranial structures (n = 12). Simultaneous systemic therapy was applied in 8 patients. Initial treatment covered the gross tumor volume with a median dose of 66 Gy (50-72 Gy) and the cervical nodal regions with a median dose of 56 Gy (50-60 Gy). Reirradiation was confined to the local relapse region with a median dose of 50.4 Gy (36-64Gy), resulting in a median cumulative dose of 112 Gy (91-134 Gy). The median time interval between initial and subsequent treatment was 52 months (6-132).ResultsThe median follow up for the entire cohort was 20 months and 31 months for survivors (10-84). Five patients (29%) developed isolated local recurrences and three patients (18%) suffered from isolated nodal recurrences. The actuarial 1- and 2-year rates of local/locoregional control were 76%/59% and 69%/52%, respectively. Six patients developed distant metastasis during the follow up period. The median actuarial overall survival for the entire cohort was 23 months, transferring into 1-, 2-, and 3-year overall survival rates of 82%, 44% and 37%. Univariate subset analyses showed significantly increased overall survival and local control for patients with less advanced rT stage, retreatment doses > 50 Gy, concurrent systemic treatment and complete response. Severe late toxicity (Grad III) attributable to reirradiation occurred in five patients (29%), particularly as hearing loss, alterations of taste/smell, cranial neuropathy, trismus and xerostomia.ConclusionReirradiation with intensity-modulated or stereotactic techniques in recurrent nasopharyngeal carcinoma is feasible and yields encouraging results in terms of local control and overall survival in patients with acceptable toxicity in patients with less advanced recurrences. However, the achievable outcome is limited in patients with involvement of intracranial structures, emphasising the need for close monitoring after primary therapy.

Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer

In this retrospective investigation we analyzed outcome and toxicity after intensity‐modulated reirradiation of recurrent head and neck cancer.