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Introduction The success of intensification and personalisation of the curative treatment of non-small cell lung cancer (NSCLC) is strongly associated with the precision in radiotherapy. Here, we evaluate the impact of radiotherapy protocol adherence in a prospective multicentre trial. Methods In the open-label, randomised, controlled PET-Plan trial, patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume delineation informed by 1F-FDG PET and CT plus elective nodal irradiation (arm A) or target volumes informed by PET alone (arm B) and received iso-toxically dose-escalated concurrent chemoradiation. The prospectively organised quality assurance program (RTQA) included individual case review by predefined criteria. For evaluation, protocol adherence was scored as per protocol (pP), with minor (miD), intermediate (inD) and major (maD) deviations. In order to exclude biases through patients who discontinued treatment, patients who received ≥60 Gy were additionally analysed. Results Between 05/2009–11/2016, 205 patients were randomized, 204 patients started treatment according to protocol of which 31 (15%) patients had maD. Patients with maD had an inferior overall survival (OS) (HR 2.9, 95% CI 1.8–4.4, p Conclusions Non-adherence to the radiotherapy protocol was associated with an inferior OS and loco-regional control. These results underline the importance of RTQA.

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board.

Background: During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a “risk-adapted” intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications. Summary: From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications. Key Message: Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI: “the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery.”

Purpose Following neoadjuvant chemotherapy for breast cancer, postoperative systemic therapy, also called post-neoadjuvant treatment, has been established in defined risk settings. We reviewed the evidence for sequencing of postoperative radiation and chemotherapy, with a focus on a capecitabine and trastuzumab emtansine (T-DM1)-based regimen. Methods A systematic literature search using the PubMed/MEDLINE/Web of Science database was performed. We included prospective and retrospective reports published since 2015 and provided clinical data on toxicity and effectiveness. Results Six studies were included, five of which investigated capecitabine-containing regimens. Of these, four were prospective investigations and one a retrospective matched comparative analysis. One randomized prospective trial was found for T‑DM1 and radiotherapy. In the majority of these reports, radiation-associated toxicities were not specifically addressed. Conclusion Regarding oncologic outcome, the influence of sequencing radiation therapy with maintenance capecitabine chemotherapy in the post-neoadjuvant setting is unclear. Synchronous administration of capecitabine is feasible, but reports on possible excess toxicities are partially conflicting. Dose reduction of capecitabine should be considered, especially if normofractionated radiotherapy is used. In terms of tolerance, hypofractionated schedules seem to be superior in terms of toxicity in concurrent settings. T‑DM1 can safely be administered concurrently with radiotherapy.

Summary Background With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer. Methods We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18F-fluorodeoxyglucose (18F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60–74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov , NCT00697333 . Findings From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9–54), the risk of locoregional progression in the 18F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% [95% CI 5–21] vs 29% [17–38] at 1 year; HR 0·57 [95% CI 0·30–1·06]). The risk of locoregional progression in the 18F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% [95% CI 9–24] vs 30% [20–39] at 1 year; HR 0·64 [95% CI 0·37–1·10]). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 [16%] of 99 patients in the conventional target group vs 17 [16%] of 105 patients in the 18F-FDG PET-based target group); the most common late toxicities were lung-related (12 [12%] vs 11 [10%]). 20 deaths potentially related to study treatment were reported (seven vs 13). Interpretation 18F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours. Funding German Cancer Aid (Deutsche Krebshilfe).

Skin-sparing (SSME) and nipple-sparing mastectomy (NSME) were developed to improve the cosmetic results for breast cancer (BC) patients, both allowing for immediate breast reconstruction. Recommendations for post-mastectomy radiotherapy (PMRT) are primarily derived from trials where patients were treated by standard mastectomies. Due to their more conservative character, SSME and especially NSME potentially leave more glandular tissue at risk for subclinical disease. Rates and sites of locoregional failures following SSME and NSME plus/minus reconstruction were analyzed regarding tumor stage and biological risk factors. In particular, the role of PMRT in “intermediate”-risk and early stage high-risk breast cancer patients was revisited. Implications on targeting and dose delivery of PMRT were critically reviewed. The value of PMRT in stage III BC remains undisputed. For node-negative BC patients, the majority of reports classify clinical and biological features such as tumor size, close surgical margins, premenopausal status, multicentricity, lymphangiosis, triple-negativity, HER2-overexpression, and poor tumor grading as associated with higher rates of locoregional relapse, thus, building an “intermediate” risk group. Surveys revealed that the majority of radiation oncologists use risk-adaptive models also considering the number of coinciding factors for the estimation of recurrence probability following SSME and NSME. Constellations with a 10-year locoregional recurrence risk of >10% are usually triggering the indication for PMRT. There was no common belief that the amount of residual tissue, e.g., tissue thickness over flaps, serves as additional decision aid. Modern treatment planning can ensure optimal dose distribution for PMRT in almost all patients with SSME. There are no reliable data supporting a reduction of the treatment volume from the CTV chest wall, e.g., to the nipple-areola complex, to the dorsal aspect behind the implant volume, the pectoralis muscle, nor the regional interpectoral, axillary, or complete regional lymph nodes only. The omission of a skin bolus in intermediate-risk BC does not compromise oncological safety. For intermediate-risk as well as early stage high-risk BC patients, the DEGRO Breast Cancer Expert Panel recommends the use of PMRT following SSME and NSME when a 10-year locoregional recurrence risk is likely to be greater than 10%, as estimated by clinical and biological risk factors. Subvolume-only radiation is discouraged outside of trials. The impact of adequate systemic treatment and the value of radiotherapy on optimal locoregional tumor control, with the goal of less than 5% LRR at 10-years follow-up, has to be verified in prospective trials.

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5‑year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40–42.5 Gy over 15–16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.

Although 2D cell cultures are commonly used to predict therapy response, it has become clear that 3D cultures may better mimic the in vivo situation and offer the possibility of tailoring translational clinical approaches. Here, we compared the response of 2D and 3D colorectal cancer (CRC) cell lines to irradiation and chemotherapy. Classic 2D cultures and 3D spheroids of CRC cell lines (CaCo2, Colo205, HCT116, SW480) were thoroughly established, then irradiated with doses of 1, 4, or 10 Gy, using a clinical-grade linear accelerator. The response was assessed by immunohistochemistry, flow cytometry, and TUNEL assays. Upon irradiation, CRC 3D spheroids were morphologically altered. After irradiation with 10 Gy, annexin V/PI staining revealed a 1.8- to 4-fold increase in the apoptosis rate in the 2D cell cultures (95% CI 3.24±0.96), and a 1.5- to 2.4-fold increase in the 3D spheroids (95% CI 1.56±0.41). Irradiation with 1 Gy caused 3- and 4-fold increases in TUNEL positive cells in the CaCo2 and HCT116 (p = 0.01) 2D cultures, respectively, compared with a 2-fold increase in the 3D spheroids. Furthermore, the 2D and 3D cultures responded differently to chemotherapy; the 3D cultures were more resistant to 5-FU and cisplatin, but not to doxorubicin and mitomycin C, than the 2D cultures. Taken together, CRC cells cultured as 3D spheroids displayed markedly higher resistance to irradiation therapy and selected chemotherapeutic drugs than 2D cultures. This in vitro difference must be considered in future approaches for determining the ideal in vitro systems that mimic human disease.

(1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1&ndash, 5, 29&ndash, 33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1&ndash, 33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician&rsquo, s discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias.

Purpose This consensus statement from the Breast Cancer Working Group of the German Society for Radiation Oncology (DEGRO) aims to define practical guidelines for accelerated partial-breast irradiation (APBI). Methods Recent recommendations for relevant aspects of APBI were summarized and a panel of experts reviewed all the relevant literature. Panel members of the DEGRO experts participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for implementing APBI in clinical routine, focusing on patient selection, target definition, and treatment technique. Results Appropriate patient selection, target definition for different APBI techniques, and basic rules for appropriate APBI techniques for clinical routine outside of clinical trials are described. Detailed recommendations for APBI in daily practice, including dose constraints, are given. Conclusion Guidelines are mandatory to assure optimal results of APBI using different techniques.

Background Late cardiac toxicities caused by (particularly left-sided) breast radiotherapy (RT) are now recognized as rare but relevant sequelae, which has prompted research on risk structure identification and definition of threshold doses to heart subvolumes. The aim of the present review was to critically discuss the clinical evidence on late cardiac reactions based on dose-dependent outcome reports for mean heart doses as well as doses to cardiac substructures. Methods A literature review was performed to examine clinical evidence on radiation-induced heart toxicities. Mean heart doses and doses to cardiac substructures were focused upon based on dose-dependent outcome reports. Furthermore, an overview of radiation techniques for heart protection is given and non-radiotherapeutic aspects of cardiotoxicity in the multimodal setting of breast cancer treatment are discussed. Results Based on available findings, the DEGRO breast cancer expert panel recommends the following constraints: mean heart dose meanLV (mean dose left ventricle) LV (volume of LV receiving ≥5 Gy) LV (volume of LV receiving ≥23 Gy) meanLAD (mean dose left descending artery) LAD (volume of LAD receiving ≥30 Gy) LAD (volume of LAD receiving ≥40 Gy) Conclusion In addition to mean heart dose, breast cancer RT treatment planning should also include constraints for cardiac subvolumes such as LV and LAD. The given constraints serve as a clinicians’ aid for ensuring adequate heart protection. The individual decision between sufficient protection of cardiac structures versus optimal target volume coverage remains in the physician’s hand. The risk of breast cancer-specific mortality and a patient’s cardiac risk factors must be individually weighed up against the risk of radiation-induced cardiotoxicity.

To review the evidence regarding post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NACT) for breast cancer, with a special focus on individualization of adjuvant radiotherapy based on treatment response. A systematic literature search using the PubMed/Medline database was performed. We included prospective and retrospective reports with a minimum of 10 patients that had been published since 1st January 2000, and provided clinical outcome data analyzed by treatment response and radiotherapy. Out of 763 articles identified via PubMed/Medline and hand search, 68 full text-articles were assessed for eligibility after screening of title and abstract. 13 studies were included in the systematic review, 9 for PMRT and 5 for RNI. All included studies were retrospective reports. There is a considerable lack of evidence regarding the role of adjuvant radiotherapy and its individualization based on treatment response after NACT. Results of prospective randomized trials such as NSABP B‑51/RTOG 1304 and Alliance A11202 are eagerly awaited.

The aim of this review was to analyze the respective efficacy of various heart-sparing radiotherapy techniques. Heart-sparing can be performed in three different ways in breast cancer radiotherapy: by seeking to keep the heart out of treated volumes (i.e. by prone position or specific breathing techniques such as deep inspiration breath-hold [DIBH] and/or gating), by solely irradiating a small volume around the lumpectomy cavity (partial breast irradiation, PBI), or by using modern radiation techniques like intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) or protons. This overview presents the available data on these three approaches. Studies on prone position are heterogeneous and most trials only refer to patients with large breasts; therefore, no definitive conclusion can be drawn for clinical routine. Nonetheless, there seems to be a trend toward better sparing of the left anterior descending artery in supine position even for these selected patients. The data on the use of DIBH for heart-sparing in breast cancer patients is consistent and the benefit compared to free-breathing is supported by several studies. In comparison with whole breast irradiation (WBI), PBI has an advantage in reducing the heart dose. Of note, DIBH and PBI with multicatheter brachytherapy are similar with regard to the dose reduction to heart structures. WBI by IMRT/VMAT techniques without DIBH is not an effective strategy for heart-sparing in breast cancer patients with “standard” anatomy. A combination of DIBH and IMRT may be used for internal mammary radiotherapy. Based on the available findings, the DEGRO breast cancer expert panel recommends the use of DIBH as the best heart-sparing technique. Nonetheless, depending on the treatment volume and localization, other techniques may be employed or combined with DIBH when appropriate.

Neoadjuvant chemotherapy (NACT) has been widely adopted into the multidisciplinary management of breast cancer. The prognostic impact of treatment response has been clearly demonstrated. However, the impact of treatment response on the indication for adjuvant radiotherapy is unclear. This review summarizes important implications of NACT and treatment response on the risk of recurrence and locoregional multidisciplinary management from the standpoint of radiation oncology.

Reasons for inferior outcome of male compared to female breast cancer are still under debate. Therefore, we retrospectively analyzed male breast cancer cases to figure out possible treatment- and gender-related differences. A total of 40 men (median age 62 years) were curatively treated with mastectomy and postoperative radiotherapy from 1982–2007. They presented predominantly in stages II and IIIb. Postoperative radiotherapy was applied with doses of 1.8–2.5 Gy to a median of 50 Gy including regional lymphatics in 22 patients. Adjuvant systemic treatment consisted of chemotherapy (22.5%) and antihormonal treatment (55%). For reasons of comparison, we estimated outcome of a virtual female matched cohort for no/equal to men/optimal adjuvant treatment with the Adjuvant!Online® 8.0 algorithm. After a median follow-up of 47 months, the estimated 5-year local control rate was 97%, disease-free and distant metastasis-free survival rates reached 79% and 82%, respectively. With update of survival data by tumor registry, mean overall survival reached 120 months with 5- and 10-year overall survival rates of 66% and 43%, respectively. Predominant prognostic factor was T-stage for overall survival (T1/2 vs. T4: > 80% vs. 30%). The generated virtual matched cohorts of women with equal characteristics reached superior 10-year-overall survival for no/equal to men/optimal adjuvant treatment with 55/59/68%. Compared to historical and virtual matched cohorts of women, male breast cancer patients had inferior outcome despite of equal stage and treatment which indicates that biological differences (of tumor or population) may contribute to worse prognosis.

In der kurativ ausgerichteten Strahlentherapie des nicht kleinzelligen Lungenkarzinoms (NSCLC) werden heute die radiosensibilisierende Wirkung einiger Chemotherapeutika wie Cisplatin und Navelbin sowie deren zusatzliche zytotoxische Effekte ausgenutzt. Weitere Verbesserungen der lokalen Tumorkontrolle des NSCLC werden durch eine genauere Zielvolumendefinition mit PET, eine Verkleinerung der Bestrahlungsvolumina uber die Reduktion von Lagerungs- und Bewegungsunsicherheiten und eine Eskalation der Bestrahlungsdosis ermoglicht.

The aim of this study was to evaluate survival rates and treatment response in stage I-IV gastric cancer in relation to tumor stage (TNM), histology, Lauren's classification and tumor localization.Clinical and histopathological data of 160 patients with stage I-IV gastric cancer were analyzed in this retrospective, single-center study.Most patients (73.1%) showed an advanced or metastatic tumor stage (III/IV). The median 3-year overall survival (OS) was 20 ± 16.8 months and correlated significantly with tumor stage (I: OS 30.6 ± 15 months vs. IV: 10.4 ± 9.3 months; p0.0001). Stage III/IV tumors were significantly more often poorly differentiated (G3; p = 0.011) and located in the corpus region. Signet ring cell (SRC) cancers were found in a larger proportion of these tumors when compared with locally limited gastric cancers (43.1% vs. 16.3%; p = 0.002). SRC tumors occurred predominantly in women and younger patients and histology was significantly more often of the diffuse subtype according to Lauren (7.5% vs. 63.2%; p0.0001) and poorly differentiated (G3 in 95% vs. 73%; p = 0.001).SRC gastric cancer correlates with poor histopathological criteria and poor prognosis when compared with other histological subtypes. These observations underline the need for more effective treatment in addition to standard approaches.

The extent and duration of routine follow-up after paraaortic (PA) radiotherapy for stage I seminoma remain controversial in terms of efficacy, costs of technical investigations and long-term morbidity. To analyze the current literature assessing routine follow-up after PA radiotherapy for stage I seminoma. We identified all published reports on PA radiotherapy for stage I seminoma (1986–2005). We analyzed time patterns of recurrence, sites and methods of detection of relapse, and follow-up programs used. We identified 11 publications reporting outcome in 2,280 patients. Median time to recurrence in 80 relapsing patients was 15.5 months. Less than 10% of recurrences were diagnosed beyond the third year of follow-up. Isolated locoregional or distant recurrence was observed in 52 and 20 patients, respectively, without significant difference in median time to relapse. 19 out of 43 recurrences with reported method of detection of relapse were diagnosed by routine technical investigations. There was no significant difference in time to relapse between those patients followed with low volume as compared to high-volume imaging protocols. Our data suggest that technical investigations in posttreatment surveillance should be restricted to the first 3 years of follow-up. Furthermore, surveillance programs with a high volume of imaging apparently do not lead to earlier detection or less advanced stage at the time of relapse as compared to protocols with low volume imaging.

Objective: To evaluate and compare positron emission tomography/ computed tomography (PET/CT) with whole-body magnetic resonance imaging (wbMRI) in the correct staging of patients with advanced nonsmall cell lung cancer (NSCLC). Materials and Methods: Fifty-two patients with an NSCLC stage IIIa or IIIb (36 males and 16 females) were included in this study. Patients were referred to our department for restaging. Within 1 week PET/CT and wbMRI were performed in all patients. Images were examined independently by 2 experienced physicians from the Department of Nuclear Medicine and Radiology. Afterward, consensus reading was performed. In 22 patients, surgery served as gold standard, whereas in 30 patients, follow-up controls (after 2 months) were performed. Results: The use of wbMRI correctly T-staged all patients. Especially volume interpolated breathhold examination sequence correctly T-staged all tumors. PET/CT did not correctly stage chest wall infiltration in 4 cases [sensitivity 92.3% (P < 0.05 to wbMRI)/ specificity 100%], verified by surgery. PET/CT correctly N-staged 51 patients (sensitivity 96.1%/specificity 100%). WbMRI showed a significant tendency to understage N-status [sensitivity 88.5% (P < 0.05)/specificity 96.1%]. Different N-status by PET/CT changed operability in 4 patients. In 2 patients, distant metastases were detected by both techniques. Conclusion: In the correct staging of advanced NSCLC, PET/CT has advantages in N-staging. This is of high relevance for therapy planning. WbMRI especially using volume interpolated breathhold examination sequences, has certain advantages in T-staging.

Purpose Adjuvant, 5-fluorouracil (5-FU)–based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods Between December 2000 and September 2003, 27 patients were treated at Tubingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m 2 ), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m 2 /24 h). A dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m 2 in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose–response relationship for renal damage in the tested dose range. Conclusions Using a dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m 2 administered before and after simultaneous 5-FU and radiotherapy.

Background To determine the outcome, acute and late toxicity in locally advanced head and neck cancer stage IVA with mitomycin-C (MMC), cisplatin (DDP) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART). Patients and methods Thirty-five patients, with squamous cell cancer of the oral cavity (20%), oropharynx (37%), hypopharynx (26%) and larynx (17%), received 30Gy (2Gy every day) followed by 1.4Gy bid to a total of 70.6Gy concurrently with MMC 10mg/m 2 (day 1 plus 36) and DDP 6mg/m 2 given Mondays through Fridays during weeks 1–3. Median follow up was 19 months. Results C-HART was given as planned in 12 of 35 patients, with radiotherapy completed per protocol in 91%. Overall, patients received 70% of the intended dose of MMC and 91% of DDP. Mucositis CTC III/IV occurred in 27%, leucopenia CTC III/IV in 47%, and three early deaths were observed. Osteoradionecrosis occurred in 14% with cT4-tumours. At 3 years the locoregional control and survival rates were 60% and 46%, respectively. Conclusion C-HART resulted in promising overall response with acceptable toxicity. Mucositis is a frequent, severe toxicity in patients treated with C-HART for head and neck cancer. While it appears that mucositis and hematological toxicity may lead to hospitalization and omitting of the second dose of mitomycin C, its impact on radiotherapy interruptions is marginal.

Background and purpose: Although head&neck and oesophageal carcinomas occur synchronously in up to 12%, almost no data on feasibility and outcome after radiotherapy are available. Materials and methods: From 1989 to 2002, 24 patients were treated at Tuebingen University and Fulda hospital with a radiation based, curative approach. These were analyzed retrospectively. Results: The median overall survival was 37 (1-69) months with a few long-term survivors with a median follow-up of 26 months for patients at risk. 7 local recurrences occured. No major toxicity was seen. Discussion: Even though the prognosis of synchronous head&neck and oesophageal carcinomas is grim, long-term survival is possible. A radiation-based approach is feasible and can be chosen for a curative treatment approach which we recommend.

Purpose: Inoperable locoregional recurrences of head-and-neck cancer in a previously irradiated volume represent a therapeutic dilemma. Chemotherapy alone has no curative potential, whereas reirradiation and concurrent chemoradiation can salvage a small fraction of patients. Mucosal toxicity of concurrent chemoradiation requires substantial dose reduction of chemotherapy. Alternating chemoradiation offers the chance to give both full-dose chemotherapy and radiotherapy. The latter may provide a particular advantage for recurrent, potentially radiation resistant tumors. The feasibility and efficacy of a full-dose docetaxel containing alternating chemoradiation schedule was tested. Patients and Methods: Twenty-seven patients (Karnofsky performance status score ≥70%) with histologically proven recurrent squamous cell cancer that occurred ≥ 6 months in a previously irradiated area (≥ 60 Gy) were considered unresectable and unsuitable for brachytherapy. Alternating chemoradiation consisted of 3 cycles of docetaxel 60 mg/m 2 d1 and cisplatin 15 mg/m 2 d2–5, q d22, and involved field radiotherapy 2.0 Gy every day d8–12, d15–19, d29–33, and d36–40 (40.0 Gy total dose). Dose reduction of docetaxel to 50 mg/m 2 was necessary, because of hematologic toxicity in the first 12 patients. Results: Alternating chemoreirradiation was applied as planned in 12 of 27 patients, with reirradiation completed per protocol in 81%. Overall, patients received 83% of the intended dose of docetaxel and 73% of cisplatin. Third-degree common toxicity criteria mucositis occurred in 15%, leukopenia of ≥ third degree by common toxicity criteria in 37%, and 3 early deaths were observed. Median time to follow-up, time to local progression, median survival, and 3-year survival rates were 42 months, 10 months, 10 months, and 18%, respectively. Conclusions: Alternating chemoreirradiation in recurrences of head-and-neck cancer resulted in 80% overall response with acceptable toxicity. A significant minority of patients had durable tumor control with a chance of long-term survival.

Purpose A German multicenter randomized trial (ARO 95-6) compared hyperfractionated accelerated radiotherapy (RT) alone (to a total radiation dose of 77.6 Gy) with hyperfractionated accelerated radiochemotherapy (to 70.6 Gy) using concurrent mitomycin C and 5-fluorouracil. We analyzed the baseline patient characteristics and the influence of physician selection bias on treatment outcome for patients who were and were not enrolled in the randomized Phase III trial, with the therapies administered according to the trial protocols. Methods and materials Between February 1996 and May 2000 at Tubingen University, 42 on-study patients and 41 off-study patients with Stage III–IV nonmetastatic squamous cell carcinoma of the head and neck were treated. The median follow-up for patients at risk (living at last evaluation) was 44 months, with a minimal follow-up of 2 years. Results The 4-year rate of overall survival, disease-specific survival, and locoregional tumor control was 25%, 40%, and 54%, respectively, for all 83 patients. Among patients enrolled in the study, the 4-year rate of overall survival for those receiving accelerated hyperfractionated radiochemotherapy was 33%, and that for patients receiving accelerated hyperfractionated RT alone was 18% ( p = 0.25); among off-study patients, the comparable rates were 48% and 0% ( p = 0.004). The 4-year rate of disease-specific survival among on-study patients receiving radiochemotherapy and RT alone was 41% and 36%, respectively ( p = 0.5); among off-study patients the respective rates were 58% and 0% ( p = 0.2). The rate of 4-year locoregional tumor control associated with radiochemotherapy and RT, respectively, was 51% and 54% among on-study patients and 72% and 23% among off-study patients ( p = 0.08). Conclusion Patients with advanced head-and-neck cancer who were entered into the randomized trial did not have statistically significantly different survival than patients treated according to the same protocol but outside the trial. Also, outside the trial, the physicians' selection bias in determining which patient received which treatment showed a much greater benefit from combined modality treatment than that found in the randomized trial.

Die postoperative Strahlentherapie des Endometriumkarzinoms erfolgt risikoadaptiert. Auf der Basis chirurgisch ermittelter Tumorausdehnung und histophatologischer Kriterien erfolgt die Identifikation von Tumoren mit erhohtem lokoregionarem Rezidivrisiko. Fur die postoperative Strahlentherapie stehen die intravaginale Brachytherapie und/oder die externe Hochvoltbestrahlung als adjuvante Therapiemasnahmen zur Verfugung. Die primare, alleinige Strahlentherapie wird heute nur bei inoperablen Tumoren oder bei erhohten pulmonalen und/oder kardialen Risiken durchgefuhrt, da durch die Operation und adjuvante Bestrahlung gunstigere Heilungsraten zu erzielen sind. Mit der modernen dreidimensionalen Bestrahlungsplanung (mittels CT/MRT) wird eine prazise Erfassung des Zielvolumens bei gleichzeitig subtiler Schonung der Risikostrukturen gewahrleistet.

Etwa 45% aller Keimzelltumoren des Hodens entfallen auf das reine Seminom. Von diesem wird heute als pathohistologische Variante nur noch das spermatozytare Seminom differenziert [28], wahrend die anaplastische Form des Seminoms in der aktuellen Klassifikation nicht mehr als eigenstandige Entitat berucksichtigt wird. Voraussetzung fur die Diagnose eines reinen Seminoms ist neben dem fehlenden Nachweis nichtseminomatoser Tumoranteile in der pathologischen Diagnostik ein praoperativ normwertig bestimmter Tumormarker AFP. Jede Erhohung dieses Markers fuhrt zur Klassifikation des Tumors als Nichtseminom, selbst wenn histologisch keine nichtseminomatosen Anteile nachweisbar sind. Im Gegensatz hierzu ist eine Erhohung des Markers β-HCG mit der Diagnose eines reinen Seminoms vereinbar. Die Prognose des β-HCG-positiven Seminoms ist im Vergleich zum Marker-negativen Seminom nicht beeintrachtigt und erfordert keine Anderung der Therapiestrategie [41].Ob dieses auch fur Tumoren mit deutlich erhohtem Marker von >1000 U/ml gilt, ist jedoch nicht geklart.

The human liver is known to be a relatively radiosensitive organ that develops clinically relevant late radiation hepatitis subsequent to whole liver treatment with total doses above 30 Gy in conventional fractionation. Experimental data, as well as clinical series, have demonstrated that hyperthermia of solid tumors in addition to radiotherapy enhances tumor growth inhibition and tumor control probability. We therefore developed an experimental model for combined radiotherapy and hyperthermia of the liver in transplantable rat Morris hepatoma 3924A.A cube of approximately 8 mm(3) was implanted subcapsularly into the middle liver lobe of 59 male syngenic ACI rats weighing approximately 180-200 g. On Day 16 after tumor implantation, irradiation of the tumor-bearing liver with either 0 Gy/25 Gy/35 Gy/45 Gy total dose in 10 fractions +/- hyperthermia (target temperature 40-42 degrees C) twice a week was initiated. Energy deposition was monitored by temperature probes in the liver and esophagus of the rats. Determination of tumor volume with magnetic resonance imaging was performed 2 to 5 weeks after the end of therapy. The tumor growth rates could be estimated for 44 rats. If the growth rate was positive (37 rats), the inverse of the growth rate was interpreted as the time to 10-fold tumor volume. Otherwise the maximum observation time was considered as a censored value in a parametric survival analysis.Intrahepatic temperature probes showed a temperature plateau of greater than 40 degrees C after 5 to 8 min subsequent to initiation of hyperthermia. The target temperatures could be maintained for at least 22 minor =40 degrees C and 10 minor =41 degrees C, respectively. Median plateau temperature in liver, esophagus, and epicutaneously was 41.2 degrees C (standard deviation [SD] 0.7 degrees C; range 38.2 to 43.3 degrees C), 40.4 degrees C (SD 1.08 degrees C; range 38.9 to 41.8 degrees C), and 40.8 degrees C (SD 0.8 degrees C; range 38.2 to 42.7 degrees C), respectively. Elevation of the temperature in the esophagus correlated with intrahepatic temperatures in the range of 39-42 degrees C, r = 0.957. The increase in time to 10-fold tumor volume for each step of irradiation dosage was by 34% (95% confidence interval [CI] 20% to 49%) without hyperthermia and by 60% (95% CI 47% to 80%) with hyperthermia (p0.0001).Treatment outcome after experimental percutaneous thermoradiotherapy in intrahepatically implanted Morris hepatoma 3924A was related to total dose of irradiation and concurrently administered regional hyperthermia. An increased radiosensitivity due to hyperthermia (42 degrees C) has to be assumed.

Radical surgery is the treatment of first choice for retroperitoneal sarcoma. However, locoregional relapse is frequently observed leading to death in the majority of patients. The role of radiotherapy is not well defined in the management of retroperitoneal sarcoma. Yet, there is evidence that adjuvant irradiation does improve local tumor control.In order to deliver sufficiently high radiation doses to the retroperitoneum, different techniques for application of a local tumor boost dose in addition to external beam treatment have been proposed. We present a technique of hyperfractionated (192)Ir brachytherapy (HFIR) of the tumor bed via intraoperatively implanted plastic catheters. Postoperative CT-based image-guided brachytherapy was performed. In two consecutive patients with recurrent retroperitoneal sarcoma, treatment was delivered twice daily with single doses of 1.5-2.0 Gy in 5-10 mm tissue depth up to a total dose of 18-32.5 Gy.HFIR of the tumor bed was easily accomplished facilitating delivery of high radiation doses to the retroperitoneum. No major late effects of treatment have been observed with a follow-up of 15 and 28 months, respectively. Details of the brachytherapy procedure are presented.HFIR via intraoperatively implanted catheters in the retroperitoneum is a technique suitable for application of a local tumor boost dose. Thus, sufficiently high doses of radiation mandatory for long-lasting local tumor control can be delivered in the tumor bed of the retroperitoneum without exceeding normal tissue radiotolerance in this unfavorable disease.

Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. Patients and Methods: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN ≥ 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0–2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. Results: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter ≥ 5 cm (p = 0.01), “close margins” or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb–III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb–III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI–Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter ≥ 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb–III) as independent predictors of poor local tumor control. Conclusion: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.

Die Indidenz des duktalen Carcinoma in situ der weiblichen Brust weist innerhalb der letzten 20 Jahre eine deutliche Zunahme auf: 1980 entfielen weniger als 3% aller Mammatumoren auf das DCIS, die Diagnose wurde uberwiegen durch histologische Abklarung eines suspekten Tastbefunds gestellt. Durch den zunehmenden Einsatz der Screening-Mammographie stellen heute etwa 20-35% aller mammographisch nachgewiesenen Tumoren ein DCIS dar [7, 24].

2-year results of a German multicenter randomized trial showed that accelerated chemoradiation with MMC/5-FU to 70.6 Gy is more effective than accelerated radiation to 77.6 Gy alone at equivalent levels of acute and late radiation morbidity. Frequency, histopathology and impact on local tumor control of selective lymph node dissection were analyzed.Between February 1996 and October 2000 at Tübingen University 42 randomized patients plus 45 non-randomized patients with stage III/IV MO head and neck cancer were treated according to this protocol. After completion of hyperfractionated accelerated (chemo-)radiation a selective lymph node dissection was performed, if the primary tumor was in complete remission and clinical plus computed tomography proved residual lymph node disease. 17 of 38 patients with residual node metastasis underwent uni- or bilateral selective node dissection, the remaining patients had residual primary tumors, clinical deterioration or refused neck dissection.After a median follow-up of 26 months, the Kaplan-Meier analysis showed a 2-year overall survival of 49%, disease-specific survival of 64% and loco-regional tumor control of 60%, respectively. 3-year loco-regional tumor control in randomized patients was 52% compared to 58% in non-randomized patients (log rank p = 0.23). 2-year loco-regional tumor control in stage cT4cN0 was 76% compared to 57% in cT2-4 cN1-3 tumors. Subgroup analysis of patients with involved nodes revealed a 2-year loco-regional tumor control of 74% after complete remission of primary tumor and neck disease, 53% after complete remission of primary tumor and partial remission of neck disease. In patients with selective lymph node dissection loco-regional tumor control was 62%. Histopathological examination showed viable tumor in eight of 17 patients.Selective lymph node dissection of residual neck masses after completion of hyperfractionated accelerated radio-(chemo-)therapy is likely to contribute to loco-regional tumor control in advanced head and neck cancer.

Purpose: To investigate the influence of gemcitabine (GEM) on acute and late toxicity of radiotherapy (XRT) in an in vivo model of acute skin reactions and late fibrotic sequelae of skin and underlying soft tissues. Methods and Materials: Single-fraction XRT was applied to the right hind leg of nude mice under ambient conditions. Single-dose GEM was applied i.p. (550 mg/kg body weight). In a first set of experiments, the influence of timing of chemotherapy relative to the onset of irradiation was investigated with GEM application 36, 24, and 2 h before and 24 h subsequent to 40 Gy XRT. With a fixed interval between chemotherapy and XRT taken from these studies, the dose-response relationship was examined for XRT in the range of 20–65 Gy. Control mice were irradiated without GEM treatment. Using a scoring system, onset, duration, and extent of acute skin reactions were analyzed. Skin fibrosis was measured by intracutaneous ink-mark separation. Soft tissue fibrosis was assessed using the leg contracture assay. ED50 calculations were performed for extent of acute and late reactions Results: Timing of GEM application relative to XRT had no significant influence on acute skin reactions or on fibrotic changes. Onset, duration, and extent of acute skin toxicity, as well as skin and leg contracture, were not significantly modulated by GEM in the dose-response experiments with GEM applied 2 h before XRT. Conclusions: Acute and late toxicity of skin and underlying soft tissues is not significantly increased after single-fraction radiotherapy in combination with GEM in the nude mice model.

Meningeal melanocytoma is a rare benign neoplasm of the central nervous system. Approximately 50% of the tumors are located intracranially with a preference for posterior fossa. We report a new case of intracranial suprasellar melanocytoma in a 57-year-old male patient treated with primary high-dose conformal radiotherapy to 50.4 Gy. Fourty-two months subsequent to treatment the tumor is well under control without neither deterioration of clinical symptoms nor progression of gross tumor volume on MR imaging. No late sequelae of treatment have been observed. A review of the literature is presented indicating that resection of melanocytoma is the treatment of first choice hampered by a relapse rate of approximately 30% depending on resection status. The role of adjuvant radiotherapy in patiens with complete resection of melanocytoma has not yet been defined. These patients carry a risk of relapse of approximately 15%, and adjuvant irradiation is currently not recommended. Primary high-dose radiotherapy has been shown to be effective in long-term control of the neoplasm in patients where no resection of the tumor could be accomplished. In case of incomplete resection of melanocytoma, data of the literature indicate that adjuvant radiotherapy may in fact increase long-term local control of the tumor. Requirements for optimal treatment results of radiotherapy are sufficiently high doses of, at least, 50 Gy for intracranial lesions and three-dimensional treatment planning guaranting precise targeting of the tumor volume with only a low-risk of late sequalae to the surrounding tissues.

A 71-year-old white male patient presented for workup of recurrent syncope. Ten years earlier, he had a diffuse large B-cell lymphoma of the stomach and successfully underwent both chemotherapy and radiation therapy (total dose, 40 Gy). Transthoracic echocardiography for the workup of syncope revealed a large left ventricular mass attached to the apex, almost completely filling the cavity of the left ventricle. The anterior mitral leaflet touched the left ventricular mass during every diastole, indicating possible hemodynamic effects (Figure 1; fully animated version in Movies I–III in the online-only Data Supplement). A contrast-enhanced computed tomography scan of the brain demonstrated a circumscribed infarction in the anterior part of the area supplied by the middle cerebral artery, suggestive of thromboembolism of a cardiac origin (Figure 2). Figure 1. Typical transthoracic echo images showing a large mass in the cavity of the left ventricle ( arrow ). Note the proximity of the left ventricular mass to the mitral valve, making contact with the anterior mitral leaflet in each diastole (Movies I–III in the online-only Data Supplement). ED indicates end-diastolic images; ES, end-systolic images; 2CV, 2-chamber view; and 4CV, 4-chamber view. Figure 2. Contrast-enhanced computed tomography (CCT) scan of the brain showing a circumscribed right hemispheric infarction (no uptake of contrast media) in the area supplied by the middle cerebral artery ( arrow ). For further noninvasive characterization of left ventricular mass (eg, thrombus versus tumor), the patient underwent cardiovascular magnetic …

This retrospective analysis investigated the effectiveness and side-effects of combined hyperthermia and radiation therapy in locally recurrent breast cancer after primary modified radical mastectomy. The aim of the thermoradiotherapy was to reduce the substantial risk of symptomatic chest wall disease.Between May 1995-August 1998, 39 extensively pre-treated women with progressive locoregional chest wall tumours were treated with local radiofrequency hyperthermia, given twice a week immediately before radiotherapy. Sixty-two per cent of the patients had received previous radiotherapy, with a median dose of 50 Gy, 64% had received chemotherapy, 36% hormonal therapy, and 13% local therapy with miltefosin, respectively. Nine patients were treated for microscopic residual disease after local tumour excision (R1-resection) and 30 patients for gross macroscopic nodular recurrences. Twenty-seven patients had two adjacent hyperthermia fields at the ipsilateral chest wall to cover the whole irradiation area. Each field received a median of seven local hyperthermia sessions (range 2-12, average 5.6 sessions) just before radiation therapy, with a median dose of 60 Gy (range 30-68 Gy). The monitored maximum(average) and average(average) epicutaneous temperatures were 42.1 degrees C and 41.0 degrees C, respectively. Maximum(average) and average(average) intratumoural temperatures of 43.0 degrees C and 41.1 degrees C, respectively, were achieved in nine chest wall recurrences with intratumoural temperature probes. Concurrent hormonal therapy was administered in 48%, and concurrent chemotherapy in 10% of patients.Median overall survival time was 28 months (Kaplan Meier), with 71% and 54% of patients living 1 and 2 years after thermoradiotherapy. The median time to local failure has not been reached, local tumour control after 2 years being 53%. Actuarial 1 and 2 year local tumour controls for microscopic residual disease were 89%, and for macroscopic nodular recurrences 71% and 46%, respectively (p = 0.09). Actuarial 1 and 2 year local tumour controls after treatment with a total dose of less than 60 Gy were 51% and 38%, respectively, and, after a total dose greater than 60 Gy, 84% and 60% (p = 0.01), respectively. Actuarial 1 year local tumour control was 92% after complete tumour remission, versus 57% after partial remission (p = 0.002). Three of the 39 patients died of cancer en cuirasse, 13 patients due to distant metastases. Acute thermoradiotherapy related erythema, dry desquamation and moist desquamation were seen in 28.2%, 30.7%, and 30.7% of patients, respectively. Soft tissue necrosis occurred in two patients with previous post-operative delayed wound healing, and in one patient above a silicon implant.This study showed that, in extensively pre-treated patients with locally recurrent breast cancer, local tumour control after thermoradiotherapy depended on tumour resectability, response of macroscopic tumour to thermoradiotherapy, and total irradiation dose.