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Purpose: Randomized trials examining neoadjuvant chemoradiotherapy followed by surgical resection (nCRT-S) and definitive CRT (dCRT) for esophageal cancer (EC) patients are hampered by use of nonstandard treatment paradigms. Outcomes of nCRT-S versus dCRT in a more common patient population are lacking. We investigated local control and survival, evaluated clinical factors associated with endpoints, and assessed patterns of failure between these cohorts.Methods: We retrospectively analyzed 130 patients with locally advanced EC receiving either dCRT or nCRT-S at our institution from 2000-2012. Inclusion criteria were curatively treated nonmetastatic EC, Karnofsky performance status ≥70%, and receipt of concomitant CRT. Patients were excluded if receiving <41 Gy neoadjuvantly or <50 Gy definitively. Kaplan-Meier analysis was used to evaluate local recurrence (LR), progression-free survival (PFS), and overall survival (OS). Univariate and multivariate Cox proportional hazards modeling addressed factors associated with outcomes. Patterns of failure were enumerated as local, regional, or distant.Results: Mean follow-up was 34.2 months. The 3‑year LR was 10.8% in the nCRT-S group and 21.5% in the dCRT group (p = 0.266). Median PFS were 15.6 and 14.9 months, respectively (p = 0.549). Median OS were 20.6 and 25.9 months, respectively (p = 0.81). On univariate and multivariate analysis, none of the investigated factors was associated with outcomes, although node-positive disease showed a trend for worse OS and PFS. Most common failures in both groups were distant (dCRT 31.2% vs. nCRT-S 21.6%) followed by local in-field recurrences (dCRT 26.9% vs. nCRT-S 10.8%).Conclusions: In this institutional analysis, no significant differences regarding outcomes and patterns of failure were observed between nCRT-S and dCRT. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate parenchymal and functional lung changes following stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) patients and to correlate radiological and functional findings with patient and treatment characteristics as well as survival. Materials and methods: Seventy patients with early-stage NSCLC treated with SBRT from 2004 to 2015 with more than 1 year of CT follow-up scans were analyzed. Incidence, morphology, severity of acute and late lung abnormalities as well as pulmonary function changes were evaluated and correlated with outcome. Results: Median follow-up time was 32.2 months with 2-year overall survival (OS) of 83% and local progression-free survival of 88%, respectively. Regarding parenchymal changes, most patients only developed mild to moderate CT abnormalities. Mean ipsilateral lung dose (MLD) in biological effective dose and planning target volume size were significantly associated with maximum severity score of parenchymal changes (p = 0.014, p < 0.001). Furthermore, both maximum severity score and MLD were significantly connected with OS in univariate analysis (p = 0.043, p = 0.025). For functional lung changes, we detected significantly reduced total lung capacity, forced expiratory volume in 1 s, and forced vital capacity (FVC) parameters after SBRT (p ≤ 0.001). Multivariate analyses revealed SBRT with an MLD ≥ 9.72 Gy and FVC reduction ≥0.54 L as independent prognostic factors for inferior OS (p = 0.029, p = 0.004). Conclusion: SBRT was generally tolerated well with only mild toxicity. For evaluating the possible prognostic impact of MLD and FVC reduction on survival detected in this analysis, larger prospective studies are truly needed. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy has a central role in the treatment of sinonasal malignancies, either as postoperative or as primary therapy. To study the efficacy and safety of intensity modulated radiotherapy (IMRT) for sinonasal tumors a single center retrospective evaluation focusing on survival and therapy related toxicity was performed.Methods: One hundred twenty two patients with primary (n = 82) or recurrent (n = 40) malignant sinonasal tumors were treated with intensity modulated radiotherapy between 1999 and 2009 at the University Clinic of Heidelberg and the German Cancer Research Center and retrospectively analyzed. Most patients had adenoid cystic carcinomas (n = 47) or squamous cell carcinoma (n = 26). 99 patients received postoperative radiotherapy. The median total dose was 64 Gy in conventional fractionation (1.8-2 Gy). Overall survival (OS), progression free survival (PFS) and local recurrence free survival (LRFS) rates were calculated using the Kaplan-Meier method. The log-rank test and Fishers Exact test were applied for univariate analysis, Cox-regression was used for multivariate analysis.Results: Median follow up was 36 months. 1-, 3- and 5-year estimated overall survival rates were 90, 70 and 54 % respectively. Median progression free survival and local recurrence free survival was 45 and 63 months respectively. Progression free survival and local recurrence free survival at 1, 3 and 5 years were 76, 57 and 47, and 79, 60 and 51 % respectively. 19 patients (15.5 %) were diagnosed with distant metastases. Univariate analysis revealed significantly improved OS and LRFS for treatment of tumors after primary diagnosis, first series of irradiation and radiation dose ≥60 Gy. Multivariate analysis revealed only treatment in primary situation as an independent prognostic factor for OS and LRFS. Acute CTC grade III mucositis was seen in 5 patients (4.1 %) and CTC grade II dysgeusia in 19 patients (15.6 %). Dysgeusia, dysosmia and ocular toxicity were the most common late adverse events.Conclusions: Our data support the results of previous studies and indicate that intensity modulated radiation therapy (IMRT) represents an effective and safe treatment approach for patients with sinonasal carcinomas. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the leading cause of cancer deaths worldwide. Surgery, radiotherapy at conventional and high dose and chemotherapy are the mainstay for lung cancer treatment. Insufficient migration and activation of tumour specific effector T cells seem to be important reasons for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer.Methods/design: This trial has been designed as an investigator-initiated, prospective, randomized, 2-armed phase II trial. Patients who are candidates for elective resection of early stage non-small cell lung cancer will be randomized into 2 arms. A total of 36 patients will be enrolled. The patients receive either 2 Gy or no radiation prescribed to their primary tumour. Radiation will be delivered by external beam radiotherapy using 3D radiotherapy or intensity-modulated radiation technique (IMRT) 7 days prior to surgical resection. The primary objective is to compare CD8+ T cell counts detected by immunohistochemistry in resected tumours following preoperative radiotherapy versus no radiotherapy. Secondary objectives include the association between CD8+ T cell counts and progression free survival, the correlation of CD8+ T cell counts quantified by immunohistochemistry and flow cytometry, local tumour control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality. Further, frequencies of tumour reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome.Discussion: This unique intervention combining preoperative low dose radiation and surgical removal of early stage non-small cell lung cancer is designed to address the problem of inadequate host anti-tumour immune response. If successful, this study may affect the role of radiotherapy in lung cancer treatment.Trial Registration: NCT02319408;Registration: December 29, 2014. [ABSTRACT FROM AUTHOR]

Background: To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123). Methods: Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6-31). Results: Median follow-up was 33 months (5-75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26-55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10-20 Gy). We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years. Conclusion: Combination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up. [ABSTRACT FROM AUTHOR]

Background: Treatment of locally advanced non-small-cell lung cancer is based on a combined approach. To study the impact of trimodal therapy for stage III-N2 NSCLC a single centre retrospective evaluation focusing on survival and therapy-related toxicity was performed. Methods: 71 patients diagnosed between March 2001 and August 2008 with pathologically confirmed stage III-N2 non-small-cell lung cancer at the University Clinic of Heidelberg were retrospectively analyzed. All patients were treated within trimodal therapy strategies including surgery, induction or adjuvant chemotherapy and postoperative radiotherapy. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. The log-rank test and Fishers Exact test were applied for univariate analysis and Cox proportional regression model for multivariate analysis. Results: Median survival was 32 months. 1-, 3- and 5-year overall survival (OS) rates were 84.5%, 49.6% and 35.5% respectively. Disease free survival rates at 1, 3 and 5 years were 70.4%, 41.8% and 27.4% respectively. 9 patients (12.6%) were diagnosed with a local recurrence. Multivariate analysis did not reveal any independent prognostic factors for OS, but indicated a trend for pT stage and type of surgery. In regard to toxicity 8.4% of the patients developed a clinically relevant ≥ grade 2 pneumonitis. Evaluation of the forced expiratory volume in 1 second per unit of vital capacity (FEV1/VC) before and 1-3 years post radiotherapy revealed a median decrease of 2.1%. Conclusions: Our descriptive data indicate that trimodal therapy represents an effective and safe treatment approach for patients with stage III-N2 non-small-cell lung cancer. Further prospective clinical trials are necessary in order to clearly define the impact of multimodal strategies and optimize NSCLC treatment. [ABSTRACT FROM AUTHOR]

Background: To report the results of a subgroup analysis of a prospective phase II trial focussing on radiation therapy and outcome in patients with extremity soft tissue sarcomas (STS). Methods: Between 2005 and 2010, 50 patients (pts) with high risk STS (size = 5 cm, deep/extracompartimental location, grade II-III (FNCLCC)) were enrolled. The protocol comprised 4 cycles of neoadjuvant chemotherapy with EIA (etoposide, ifosfamide and doxorubicin), definitive surgery with IOERT, postoperative EBRT and 4 adjuvant cycles of EIA. 34 pts, who suffered from extremity tumors and received radiation therapy after limb-sparing surgery, formed the basis of this subgroup analysis. Results: Median follow-up from inclusion was 48 months in survivors. Margin status was R0 in 30 pts (88%) and R1 in 4 pts (12%). IOERT was performed as planned in 31 pts (91%) with a median dose of 15 Gy, a median electron energy of 6 MeV and a median cone size of 9 cm. All patients received postoperative EBRT with a median dose of 46 Gy after IOERT or 60 Gy without IOERT. Median time from surgery to EBRT and median EBRT duration was 36 days, respectively. One patient developed a local recurrence while 11 patients showed nodal or distant failures. The estimated 5-year rates of local control, distant control and overall survival were 97%, 66% and 79%, respectively. Postoperative wound complications were found in 7 pts (20%), resulting in delayed EBRT (>60 day interval) in 3 pts. Acute radiation toxicity mainly consisted of radiation dermatitis (grade II: 24%, no grade III reactions). 4 pts developed grade I/II radiation recall dermatitis during adjuvant chemotherapy, which resolved during the following cycles. Severe late toxicity was observed in 6 pts (18%). Long-term limb preservation was achieved in 32 pts (94%) with good functional outcome in 81%. Conclusion: Multimodal therapy including IOERT and postoperative EBRT resulted in excellent local control and good overall survival in patients with high risk STS of the extremities with acceptable acute and late radiation side effects. Limb preservation with good functional outcome was achieved in the majority of patients. [ABSTRACT FROM AUTHOR]

Background: We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT). Methods: The medical records of 49 patients with histologically proven primary nasopharygeal carcinoma treated with IMRT and concurrent platin-based CHT (predominantly cisplatin weekly) were retrospectively reviewed. The majority of patients showed advanced clinical stages (stage III/IV:72%) with undifferentiated histology (82%). IMRT was performed in step-and-shoot technique using an integrated boost concept in 84%. In this concept, the boost volume covered the primary tumor and involved nodes with doses of 66-70.4 Gy (single dose 2.2 Gy). Uninvolved regional nodal areas were covered with doses of 54-59.4 Gy (median single dose 1.8 Gy). At least one parotid gland was spared. None of the patients received adjuvant CHT. Results: The median follow-up for the entire cohort was 48 months. Radiation therapy was completed without interruption in all patients and 76% of the patients received at least 80% of the scheduled CHT. Four local recurrences have been observed, transferring into 1-, 3-, and 5-year Local Control (LC) rates of 98%, 90% and 90%. One patient developed an isolated regional nodal recurrence, resulting in 1-, 3-, and 5-year Regional Control (RC) rates of 98%. All locoregional failures were located inside the radiation fields. Distant metastases were found in six patients, transferring into 1-, 3, and 5-year Distant Control (DC) rates of 92%, 86% and 86%. Progression free survival (PFS) rates after 1, 3 and 5 years were 86%, 70% and 69% and 1-, 3- and 5-year Overall Survival (OS) rates were 96%, 82% and 79%. Acute toxicity = grade III mainly consisted of dysphagia (32%), leukopenia (24%), stomatitis (16%), infection (8%) and nausea (8%). Severe late toxicity (grade III) was documented in 18% of the patients, mainly as xerostomia (10%). Conclusion: Concurrent chemoradiation without the addition of adjuvant chemotherapy cycles using IMRT with an integrated boost concept yielded good disease control and overall survival in patients suffering from primary nasopharyngeal cancer with acceptable acute side effects and limited rates of late toxicity. [ABSTRACT FROM AUTHOR]

Background: While evidence on safety and efficacy of primary hypofractionated radiotherapy in prostate cancer is accumulating, data on postoperative hypofractionated treatment of the prostate bed and of the pelvic lymphnodes is still scarce. This phase II trial was initiated to investigate safety and feasibility of hypofractionated treatment of the prostate bed alone or with the pelvic lymph nodes.Methods/design: A total of 80 prostate cancer patients with the indication for adjuvant radiotherapy will been rolled, where 40 patients with a low risk of lymph node involvement (arm 1) and another 40 patients with a high risk of lymph node involvement (arm 2) will each receive 54 Gy in 18 fractions to the prostate bed. Arm 2will be given 45 Gy to the pelvic lymph nodes additionally. Helical Tomotherapy and daily image guidance will be used.Discussion: This trial was initiated to substantiate data on hypofractionated treatment of the prostate bed and generate first data on adjuvant hypofractionated radiotherapy of the pelvic lymph nodes.Trial registration: ClinicalTrials.gov; NCT01620710 [ABSTRACT FROM AUTHOR]

Background: To evaluate the use of intraoperative radiation therapy (IORT) in the multimodality treatment of patients with isolated local recurrences of pancreatic cancer. Methods: We retrospectively analyzed 36 patients with isolated local recurrences of pancreatic cancer who have been treated with a combination of surgery, IORT and EBRT. Median time from initial treatment to recurrence was 20 months. All patients were surgically explored. In 18 patients a gross total resection was achieved, whereas the other half received only debulking or no resection at all. All patients received IORT with a median dose of 15 Gy. Additional EBRT was applied to 31 patients with a median dose of 45 Gy, combined with concurrent, mainly gemcitabine-based chemotherapy. Results: Median follow-up in surviving patients was 23 months. Local progression was found in 6 patients after a median time of 17 months, resulting in estimated 1- and 2-year local control rates of 91% and 67%, respectively. Distant failure was observed in 23 patients, mainly in liver or peritoneal space. The median estimated progression-free survival was 9 months with 1- and 2-year rates of 40% and 26%, respectively. We found an encouraging estimated median overall survival of 19 months, transferring into 1- and 2-year rates of 66% and 45%. Notably 6 of 36 patients (17%) lived for more than 3 years. Severe postoperative complications were found in 3 and chemoradiation-related grade III toxicity in 6 patients. No severe IORT related toxicity was observed. Conclusion: Combination of surgery, IORT and EBRT in patients with isolated local recurrences of pancreatic cancer resulted in encouraging local control and overall survival in our cohort with acceptable toxicity. Our approach seems to be superior to palliative chemotherapy or chemoradiation alone and should be further investigated in a prospective setting specifically addressing isolated local recurrences of pancreatic cancer. [ABSTRACT FROM AUTHOR]

The article focuses on a study about the use of stereotactic single-dose radiotherapy in treating stages I and II of nonsmall-cell lung cancer (NSCLC). 42 patients administered with radiosurgery were treated in a stereotactic body frame while breathing motion was lessen by abdominal compression. Results show that overall survival rate was at 37.4% and disease-free survival rate at 49.1% at 36 months following therapy. It concludes that the radiotherapy can be an option for patients not suitable for surgery.

Background: The prognosis for patients with advanced epithelial ovarian cancer remains poor despite aggressive surgical resection and platinum-based chemotherapy. More than 60% of patients will develop recurrent disease, principally intraperitoneal, and die within 5 years. The use of whole abdominal irradiation (WAI) as consolidation therapy would appear to be a logical strategy given its ability to sterilize small tumour volumes. Despite the clinically proven efficacy of whole abdominal irradiation, the use of radiotherapy in ovarian cancer has profoundly decreased mainly due to high treatment-related toxicity. Modern intensity-modulated radiation therapy (IMRT) could allow to spare kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Methods/Design: The OVAR-IMRT-01 study is a single center pilot trial of a phase I/II study. Patients with advanced ovarian cancer stage FIGO III (R1 or R2< 1 cm) after surgical resection and platinum-based chemotherapy will be treated with whole abdomen irradiation as consolidation therapy using intensity modulated radiation therapy (IMRT) to a total dose of 30 Gy in 1.5 Gy fractions. A total of 8 patients will be included in this trial. For treatment planning bone marrow, kidneys, liver, spinal cord, vertebral bodies and pelvic bones are defined as organs at risk. The planning target volume includes the entire peritoneal cavity plus pelvic and para-aortic node regions. Discussion: The primary endpoint of the study is the evaluation of the feasibility of intensity-modulated WAI and the evaluation of the study protocol. Secondary endpoint is evaluation of the toxicity of intensity modulated WAI before continuing with the phase I/II study. The aim is to explore the potential of IMRT as a new method for WAI to decrease the dose to kidneys, liver, bone marrow while covering the peritoneal cavity with a homogenous dose, and to implement whole abdominal intensity-modulated radiotherapy into the adjuvant multimodal treatment concept of advanced ovarian cancer FIGO stage III. [ABSTRACT FROM AUTHOR]

• Retrospective analysis of the first clinical data on carbon ion radiation in pancreatic cancer in Europe (at the HIT) • Dose to delivered to the tumor according to HIT standards matches NIRS standards within 4%: a median D 50\% of 53.18 G y R B E NIRS in the ITV. • Median LETd 98% in the total cohort 40.50 keV/μm. • Increase in the dose constraint to the gastrointestinal tract (from D max < 45.6 Gy R B E HIT to D 1cm 3 < 49 Gy R B E HIT ) could be considered to improve local control, without leading to a significant increase toxicity in the patients. To analyze the dose objectives and constraints applied at the prospective phase II PACK-study at Heidelberg ion therapy center (HIT) for different radiobiological models. Treatment plans of 14 patients from the PACK-study were analyzed and recomputed in terms of physical, biological dose and dose-averaged linear energy transfer (LETd). Both LEM-I (local effect model 1) and the adapted NIRS-MKM (microdosimetric kinetic model), were used for relative biological effectiveness (RBE)-weighted dose calculations (D Bio | HIT and D Bio | NIRS). A new constraint to the gastrointestinal (GI) tract was derived from the National Institute of Radiological Science (NIRS) clinical experience and considered for plan reoptimization (D Bio | NIRS - const_ 48 Gy and D Bio | NIRS - const_ 50. 4 Gy). The Lyman-Kutcher-Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for GI toxicity endpoints was computed. Furthermore, the computed LETd distribution was evaluated and correlated with Local Control (LC). Only two patients showed a LETd 98% in the GTV greater than 44 keV/μm. A HIT-dose constraint to the GI of D 2 cm 3 = 48. 6 Gy RBE HIT was derived from the NIRS experience, in alternative to the standard at HIT D max = 45.6 Gy RBE HIT. In comparison with the original D Bio | HIT , D Bio | NIRS - const_ 48 Gy and D Bio | NIRS - const_ 50. 4 Gy resulted in an increase in the ITV's D 98% of 8.7% and 11.3%. The NTCP calculation resulted in a probability for gastrointestinal bleeding of 4.5%, 12.3% and 13.0%, for D Bio | NIRS , D Bio | NIRS - const_ 48 Gy and D Bio | NIRS - const_ 50. 4 Gy , respectively. The results indicate that the current standards applied at HIT for CIRT closely align with the Japanese experience. However, to enhance tumor coverage, a more relaxed constraint on the GI tract may be considered. As the PACK-trial progresses, further analyses of various clinical endpoints are anticipated. [ABSTRACT FROM AUTHOR]

Background and purpose To report our experience with limb-sparing surgery, IOERT and EBRT in extremity STS. Materials and methods 183 patients were retrospectively analyzed. 78% presented in primary situation, with 80% located in the lower limb. Stage at presentation was: I: 6%, IIa: 25%, IIb: 21%, III: 42%, IV: 7%. The majority showed high-grade lesions (grade 1: 5%, 2: 31%, 3: 64%). IOERT was applied to the tumor bed (median 15 Gy) and preceded (9%) or followed (91%) by EBRT (median 45 Gy) in all patients. Results Median follow-up was 64 months (78 months in survivors). Surgery was complete in 68%, while 32% had microscopic residual disease. 5- and 10-year-LC was 86% and 84%, respectively. LC was significantly higher in primary compared to recurrent disease and tended to be higher after complete resection. Estimated 5- and 10-year-DC was 68% and 66%, while corresponding OS was 77% and 66%, respectively. OS was significantly affected by grading and stage. Severe postoperative complications and late toxicities were observed in 19% and 20%, respectively. Limb-preservation rate was 95% with good function in 83%. Conclusions Combination of limb-sparing surgery, IOERT and EBRT achieved encouraging LC and OS in this unfavorable patient group with acceptable postoperative complications and low rates of late toxicities resulting in a high limb-preservation rate and good functional outcome. [ABSTRACT FROM AUTHOR]

Purpose: Salvage radiotherapy (RT) is used to treat patients with biochemical failure after radical prostatectomy (RP). Although retrospective series have demonstrated that salvage RT will result in biochemical response in approximately 75% of patients, long-term response is much lower (20–40%). The purpose of this study was to determine prognostic factors related to the prostate-specific antigen (PSA) outcome after salvage RT. Methods and Materials: Between 1991 and 2004, 171 patients received salvage RT at the University of Heidelberg. Patient age, margin status, Gleason score, tumor grading, pathologic tumor stage, pre-RP and pre-RT PSA levels, and time from RP to rise of PSA were analyzed. Results: Median follow-up time was 39 months. The 5-year overall and clinical relapse-free survival were 93.8% and 80.8%, respectively. After RT serum PSA decreased in 141 patients (82.5%). The 5-year biochemical relapse-free survival was 35.1%. Univariate analysis showed following statistically significant predictors of PSA recurrence after RT: preoperative PSA level (p = 0.035), pathologic tumor classification (p = 0.001), Gleason score (p < 0.001), tumor grading (p = 0.004), and pre-RT PSA level (p = 0.031). On multivariate analysis, only Gleason score (p = 0.047) and pre-RT PSA level (p = 0.049) were found to be independently predictive of PSA recurrence. Conclusions: This study represents one of the largest retrospective studies analyzing the outcome of patients treated with salvage RT at a single institution. Our findings suggest that patients with Gleason score <7 and low pre-RT PSA levels are the best candidates for salvage RT, whereas patients with high-grade lesions should be considered for additional treatment (e.g., hormonal therapy). [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: Purpose: Brachytherapy re-irradiation may offer an alternative re-treatment of recurrent head-and-neck cancer even after previous full dose radiation therapy. The purposes of this study were to determine the feasibility and accuracy of frameless image-guided interstitial needle implantation. Methods and materials: Between January 2000 and March 2003, 14 patients with biopsy-proven locally recurrent head-and-neck-cancer were retreated after previous full dose irradiation with combined external beam-brachytherapy with concomitant chemotherapy. Brachytherapy needle implantation was virtually planned taking into account the surrounding risk structures. Needles were implanted using an adapted frameless navigation system. Chemoradiotherapy was followed by 2–4 courses of chemotherapy every fourth week starting 4 weeks after the end of brachytherapy. Results: The 1- and 2-year local control rates were 78% and 57%, respectively. Local control was obtained in 8/14 patients. The actuarial 1- and 2-year survival rates were 83% and 64%, respectively. The median survival was 28 months after a median follow-up of 21 months (range, 8–53). Six weeks after brachytherapy, 1 patient developed localized soft tissue necrosis which did not require surgical intervention. No additional grade III or IV late toxicity was seen after re-irradiation. Mean deviation of image-guided needle implantation was 3.4 mm for each needle (SD, 1.9 mm; range, 0.5–14 mm). The mean deviation of all needles of an implant was 4.3 mm (range, 2.3–8.6 mm). Conclusions: These data demonstrate that pulsed-dose-rate brachytherapy in combination with sequential chemotherapy is effective and safe in re-irradiation of locally recurrent oropharyngeal carcinomas and can be offered to patients with curative intent. Image guidance allows virtual planning and navigated implantation of brachytherapy needles with regard to optimized needle distribution and risk structures. [Copyright &y& Elsevier]