Low risk of contralateral lymph node recurrence in lateralized head and neck carcinoma after postoperative ipsilateral radiotherapy.

PURPOSE: The role of postoperative irradiation to contralateral non-involved neck nodes in lateralized carcinoma of the head and neck is not clear. The contralateral neck failure rate in head and neck carcinoma treated postoperatively with ipsilateral neck irradiation only was evaluated. METHODS: Patients with carcinoma of the oral cavity, oropharynx, or hypopharynx without midline extension treated between 1990 and 2016 were analyzed. After tumor resection and neck dissection (ND), radiotherapy was given to the primary tumor site and ipsilateral neck. High-risk patients additionally received concurrent chemotherapy. Freedom from contralateral neck recurrence (FCNR), locoregional control rate (LRC), overall survival (OS), and disease-free survival (DFS) were evaluated. RESULTS: 197 patients (median age 60.7 years, 66.5% males, 52.8% oropharyngeal carcinomas) were analyzed. Complete resection (R0) was achieved in 85.8% of cases. Ipsilateral ND was performed in all patients and contralateral ND in 144 patients (73.1%). Concurrent chemotherapy was given to 59 patients (30.0%). After a median follow-up of 45.5 months, OS and DFS of all patients were 73.6% and 70.9% at 5 years, respectively. A total of 45 patients (22.8%) suffered from a locoregional recurrence, lymph node metastases of the contralateral neck developed in 12 patients (6.1%) only. There was no significant difference in contralateral nodal failure rate with or without performance of contralateral ND. CONCLUSION: Regional failure of the contralateral neck was low after surgery and ipsilateral neck irradiation in head and neck carcinomas without midline extension, supporting evidence that contralateral neck radiotherapy can safely be omitted in selected cases.

Neoadjuvant chemoradiation for patients with advanced oesophageal cancer - which response grading system best impacts prognostic discrimination?

AIMS: Neoadjuvant chemoradiation reduces tumour volume and improves the R0 resection rate, followed by extended survival for patients with advanced oesophageal cancer. The degree of tumour regression has high prognostic relevance. To date, there is still no generally accepted tumour regression grading system. The aim of this study was to compare the prognostic discrimination power of different histological regression grading systems: (i) the fibrosis/tumour ratio within the primary tumour (Mandard classification), (ii) the percentage of residual vital tumour cells (VTC) compared to the original primary tumour (Cologne Regression) and (iii) the ypT category, in patients with cT3 carcinoma of the oesophagus after neoadjuvant chemoradiation. METHODS AND RESULTS: This study included 216 patients with oesophageal cancer clinically staged as cT3NxM0 and treated from 2009 to 2012 with standardised chemoradiation followed by oesophagectomy [median age 62 years, 176 (81%) male and 138 (64%) adenocarcinoma patients]. The subgroup frequencies of the three classification systems were ypT category: ypT0 = 18%, ypT1 = 14%, ypT2 = 23%, ypT3 = 44%, ypT4 = 1%; Mandard classification: TRG1 = 18%, TRG2 = 26%, TRG3 = 24%, TRG4 = 30%, TRG5 = 2%; and Cologne Regression Scale: no tumour = 18%, 1-10% VTC = 27%, 10-50% VTC = 26% and >50% VTC = 29%. The Mandard and Cologne Regression classifications showed better prognostic differentiation for the subgroups than the ypT category. The four-tiered Cologne Regression system had a good prognostic relevance. Comparing results of the re-evaluated Cologne Regression classification with the classification by routine pathological report showed very good inter-rater agreement, with kappa value 0.891. CONCLUSION: Compared to the original primary tumour, the tumour regression grading system using the percentage of residual vital tumour has prognostic relevance.

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer.

PURPOSE: To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients. METHODS: From 2012 to 2016, 106 patients (median age 74 years, range 50-94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1-3 cm) in 86 patients (81%) and IIA (T2a/b, 3-5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%. RESULTS: Median follow-up was 15 months (range 0.5-46 months). Acute side effects were mild (fatigue grade 1-2 in 20% and dyspnea grade 1-2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80-96%) at 2 years and 77% (95%CI 56-98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23-31 months). Overall survival was 77% (95%CI 65-85%) at 2 years and 56% (95%CI 39-73%) at 3 years. CONCLUSION: CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial.

BACKGROUND: The role of bleomycin and dacarbazine in the ABVD regimen (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) has been questioned, especially for treatment of early-stage favourable Hodgkin's lymphoma, because of the drugs' toxicity. We aimed to investigate whether omission of either bleomycin or dacarbazine, or both, from ABVD reduced the efficacy of this regimen in treatment of Hodgkin's lymphoma. METHODS: In this open-label, randomised, multicentre trial (HD13) we compared two cycles of ABVD with two cycles of the reduced-intensity regimen variants ABV (doxorubicin, bleomycin, and vinblastine), AVD (doxorubicin, vinblastine, and dacarbazine), and AV (doxorubicin and vinblastine), in patients with newly diagnosed, histologically proven, classic or nodular, lymphocyte predominant Hodgkin's lymphoma. In each treatment group, 30 Gy involved-field radiotherapy (IFRT) was given after both cycles of chemotherapy were completed. From Jan 28, 2003, patients were centrally randomly assigned (1:1:1:1) with a minimisation method to the four groups. Because of high event rates, assignment to the AV and ABV groups stopped early, on Sept 30, 2005, and Feb 10, 2006; assignment to ABVD and AVD continued (1:1) until Sept 30, 2009. Our primary objective was to show non-inferiority of the experimental variants compared with ABVD in terms of freedom from treatment failure (FFTF), by excluding a difference of 6% after 5 years corresponding to a hazard ratio (HR) of 1.72, via a 95% CI. Analyses reported here include qualified patients only, and between-group comparisons include only patients recruited during the same period. The trial was registered, number ISRCTN63474366. FINDINGS: Of 1502 qualified patients, 566, 198, 571, and 167 were randomly assigned to receive ABVD, ABV, AVD, or AV, respectively. 5 year FFTF was 93.1%, 81.4%, 89.2%, and 77.1% with ABVD, ABV, AVD, and AV, respectively. Compared with ABVD, inferiority of the dacarbazine-deleted variants was detected with 5 year differences of -11.5% (95% CI -18.3 to -4.7; HR 2.06 [1.21 to 3.52]) for ABV and -15.2% (-23.0 to -7.4; HR 2.57 [1.51 to 4.40]) for AV. Non-inferiority of AVD compared with ABVD could also not be detected (5 year difference -3.9%, -7.7 to -0·1; HR 1.50, 1.00 to 2.26). 178 (33%) of 544 patients given ABVD had WHO grade III or IV toxicity, compared with 53 (28%) of 187 given ABV, 142 (26%) of 539 given AVD, and 40 (26%) of 151 given AV. Leucopenia was the most common event, and highest in the groups given bleomycin. INTERPRETATION: Dacarbazine cannot be omitted from ABVD without a substantial loss of efficacy. With respect to our predefined non-inferiority margin, bleomycin cannot be safely omitted either, and the standard of care for patients with early-stage favourable Hodgkin's lymphoma should remain ABVD followed by IFRT. FUNDING: Deutsche Krebshilfe and Swiss State Secretariat for Education and Research.

Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial.

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

Impact of centralized diagnostic review on quality of initial staging in Hodgkin lymphoma: experience of the German Hodgkin Study Group.

Accurate clinical staging is crucial for adequate risk-adapted treatment in Hodgkin lymphoma (HL) to prevent patients from under- or over-treatment. Within the latest German Hodgkin Study Group trial generation, diagnostic findings such as histopathology, computerized tomography imaging and clinical risk factors were re-evaluated by expert panels. Here, we retrospectively analysed 5965 patients and identified 399 in who major discordant findings changed their first-line treatment allocation. Histopathology review did not confirm the initial diagnosis of HL in 87 patients. Treatment allocation was revised in 312 of the remaining 5878 patients: 176 were assigned to a higher and 128 to a lower risk group, respectively; the correct treatment group remained unclear in 8 patients. Cases of revised treatment allocation accounted for 9·8%, 6·0%, 0·8%, and 14·8% of patients initially assigned to the HD13, HD14, HD15 trials and stage IA lymphocyte-predominant HL project, respectively. Most revisions were due to wrong application of clinical stage (20·5% of 312 patients with revised treatment group), histological subtype (9·0%) or the risk factors ≥3 involved areas (46·8%) or large mediastinal mass (9·3%). In conclusion, centralized review by experienced experts changed risk-adapted first-line treatment in a relevant proportion of HL patients. Quality control measures clearly improve the accuracy of treatment and should be implemented in clinical practice.

Expression of podoplanin and prognosis in oropharyngeal cancer.

It has been shown that podoplanin expression is associated with carcinoma of the aerodigestive tract. Recent studies indicate that podoplanin may serve as a prognostic biomarker in oral carcinoma. In order to provide evidence on the role of podoplanin in oropharyngeal squamous cell carcinoma, we evaluated the prognostic impact of podoplanin in these patients. We analyzed formalin-fixed tissue samples from 107 consecutive patients with oropharyngeal squamous cell carcinoma. HPV typing and immunohistochemical staining for both p16 and podoplanin were performed. Expression of podoplanin was seen in 38.3% of all cases. We found no correlation of the podoplanin scores with either p16 expression or with HPV status. There was no significant correlation of podoplanin expression with the staging variables T, N, M, and tumor grading. Podoplanin expression did neither influence the 5-year overall survival nor the 5-year disease-free survival. Concluding, we could not find a prognostic role of podoplanin expression neither in the HPV-positive cases nor in the HPV-negative cases. It appears that podoplanin is not expressed as often in oropharyngeal cancer compared to oral cancer. We could not show any relation of lymph node metastases and podoplanin expression in this homogenous cohort of tumors.

Management of neck metastases of unknown primary origin united in two European centers.

Combined analysis of diagnostic and therapeutic management of neck metastases of carcinoma of unknown primary origin ('true CUP') in two European tertiary referral centers (University Medical Centers of Maastricht, NL and Cologne, D) to contribute to the ongoing discussion on management in CUP. Retrospective analysis of 29 (Maastricht) and 22 (Cologne) true cervical CUP syndrome patients (squamous cell carcinoma). The diagnostic and therapeutic approaches were correlated with clinical follow-up data and HPV status. In total, 48 out of 51 true CUP patients received postsurgical adjuvant radiotherapy. In eight patients from Cologne, this was combined with concomitant platin-based chemotherapy. Neither in Cologne nor in Maastricht, radiotherapy of the pharyngeal mucosa was commonly performed (n = 6, 12.5 %) The percentage of patients who were irradiated ipsilaterally or bilaterally did not differ between both institutes (N = 21/27 in Maastricht vs. 11/21 in Cologne), nor did the 5-year overall survival differ significantly. Oncogenic HPV was only found in 4 out of 51 CUPs (7, 8 %). Therefore, no relation with overall and recurrence-free survival could be detected. No occult primary tumors were revealed during follow-up despite de-escalation of therapy by abandoning irradiation of the pharyngeal mucosa in both institutes. There were no significant differences between ipsilateral and bilaterally irradiated patients regarding overall and recurrence-free survival. The occurrence of distant metastases was more often noticed in ipsilaterally treated patients as compared to bilaterally radiated patients (8 vs. 2, p = 0.099). Those patients all had been classified N2b or higher. International guidelines still are not unified and there is an urgent need for a consented therapeutic regimen. Comparison of two international strategies on the management of CUP patients is presented and further research is recommended regarding the role of radiotherapy of the pharyngeal axis, the value of unilateral and bilateral radiotherapy and the role of concomitant or induction chemotherapy in CUP patients, particularly in N2b or higher-staged neck disease. The prevalence and role of HPV in true CUP after thorough diagnostic work-up seem limited in our case series, particularly when compared to the role in oropharyngeal carcinomas.

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel : a phase II study.

PURPOSE: To report outcome and toxicity of concurrent radiochemotherapy with carboplatin and paclitaxel in advanced squamous cell carcinomas of the oropharynx and hypopharynx. PATIENTS AND METHODS: Advanced inoperable carcinomas of the oropharynx and hypopharynx were treated with either hyper-fractionated, accelerated radiotherapy (50.0 Gy/2.0 with concomitant boost to 69.2 Gy/1.6) or conventional fractionated radiotherapy (70.2-72 Gy/1.8) concurrent with paclitaxel 40 mg/m2 and carboplatin AUC 1 weekly for 6 weeks. Acute and long-term toxicity was measured according to WHO- and CTC-criteria. RESULTS: A total of 84 patients were included between 2000 and 2008. Median follow-up time of patients alive was 36 months. Conventionally fractionated radiotherapy was given to 16 patients, while 68 patients were treated with concomitant boost. Finally, 88.1% of patients received full dose paclitaxel. Acute mucositis ≥ grade 3 was present in 51.2% of patients, while 6% of patients experienced ≥ grade 3 leucopenia and thrombopenia. A supportive gastric feeding tube was implanted in 89.1% of patients. Overall survival after 2 years was 46.3%, progression-free survival after 2 years was 41.0%. There was no significant survival difference between the different radiotherapy protocols. CONCLUSION: Concomitant carboplatin and paclitaxel is feasible and effective in advanced carcinomas of the head and neck.

Survival after parotid gland metastases of cutaneous squamous cell carcinoma of the head and neck.

PURPOSE: Malignant tumours in the parotid gland can originate either from the gland itself or as a result of metastatic spread of other tumours, such as cutaneous squamous cell carcinomas (CSCC) of the head and neck area. The aim of this study was to analyse and compare the clinical behaviour of primary as well as CSCC metastatic parotid cancers with special emphasis on therapy and oncologic outcome. METHODS: Clinical and histopathological data of 342 patients with parotid gland malignomas surgically treated in a tertiary referral centre between 1987 and 2015 were retrospectively assessed. Oncologic outcomes of all cases with CSCC metastasis of the parotid gland (n = 49) were compared to those of primary parotid gland carcinomas (n = 293). RESULTS: Mean age at diagnosis was 72.3 years for CSCC patients versus 56.8 years in patients with primary parotid carcinoma. A total of 83.7% of CSCC patients were male, compared to 48.8% in the group of primary carcinomas. Forty-five out of 49 CSCC patients underwent total parotidectomy and neck dissection (91.8%). A total of 93.9% out of all CSCC patients received adjuvant radiotherapy. Five-year overall survival (OS) was 32.6% in CSCC patients versus 77.2% in primary parotid carcinoma patients. CONCLUSION: As compared to primary parotid cancers, we could show that patients suffering from CSCC metastases to the parotid gland presented with significantly higher age and worse survival.

[Training in radiation oncology in Germany. Current status and necessary developments]. / Weiterbildung zum Facharzt für Strahlentherapie in Deutschland : Aktueller Status und notwendige Entwicklungen.

BACKGROUND AND PURPOSE: A sufficient number of well-trained specialists in radiation oncology is needed for an adequate supply in radiation oncology. Therefore, the training in radiation oncology is of utmost importance. This requirement is faced with a growing lack of physicians in Germany. The aim of this study was to characterize the current situation of radiation oncology training in Germany and to work out proposals to avoid a lack of radiotherapists. MATERIAL AND METHODS: In summer 2008, 233 questionnaires were sent out to potential trainers in radiation oncology in Germany. The questions included, among others, the individual training situation and problems in finding physicians. A second questionnaire was addressed to trainees in radiation oncology and contained, e.g., questions regarding satisfaction, motivation for the choice of radiation oncology, a previous work in another discipline, and future perspectives. RESULTS: Answers were obtained from 107 supervisor physicians of whom 84.1% had the permission to employ trainees in radiation oncology. The finding of new trainees provided large problems in 47.1%; 35.3% had few and 17.6% no problems. For specialists in radiation oncology, 47.2% reported large, 26.4% few and 26.4% no problems in finding candidates. 113 trainees answered the questionnaires. Almost half of them (46.9%) had previously worked in another discipline. The majority was quite (44.2%) or fully (46.0%) satisfied with their job, 84.1% stated good up to excellent future perspectives. The vast majority (88.5%) would decide for a training in radiation oncology again. CONCLUSION: Trainees in radiation oncology in Germany are satisfied with their training, see good future perspectives and would again decide to do their training in radiation oncology. However, there are large problems in finding candidates for open jobs. A positive promotion is recommended to face these problems.

Volumetric assessment of mediastinal lymphoma masses in Hodgkin lymphoma.

The large mediastinal mass (LMM) at initial staging represents a risk factor in Hodgkin lymphoma (HL) and is measured by X-ray. Depending on location of the LMM, different results can occur regardless of the initial lymphoma volume. To assess this risk factor more accurately, we evaluated the method of volumetry in 77 patients of HD13/14 study of the German Hodgkin Study Group. Furthermore, volume calculations based on three or only one diameter, were performed to simplify volume assessment. Inter-rater reliability was good for all methods. The 3-diameter measurement produced larger volumes than volumetric assessment with an intraclass correlation coefficient (ICC) of 0.93, which could be improved to 0.95 by multiplying volumes with a correction factor of 0.86. The 1-dimensional measurement strongly overestimated the volume with an ICC of 0.7. In conclusion, the simplified volume estimation based on 3 largest diameters provides a reliable concept for the staging of HL patients.

Outcome of multimodal treatment for oropharyngeal carcinoma: a single institution experience.

The clinical management of patients with primary oropharyngeal squamous cell carcinoma remains controversial. The results of a combined approach involving surgery for the primary tumor, neck dissection, and postoperative radiotherapy were reviewed. A retrospective review was carried out for 211 patients meeting the inclusion criteria of resectable squamous cell carcinoma of the oropharynx. Overall survival and disease-free survival rates were calculated using the Kaplan-Meier method. Univariate (Log-rank test) and multivariate (Cox proportional hazards models) statistical analyses were carried out to investigate the role of clinical factors as significant prognostic markers. The 2- and 5-year disease-free survival rates were 79.8% and 68.8%, respectively. In univariate and multivariate analyses, positive resection margins were the only and independent significant prognostic markers for impaired disease-free survival (Log-rank: p=0.0238; Cox model: p=0.045; hazard ratio 2.48 [95% confidence interval 1.02-6.05]). In univariate analysis, male sex was the only significant negative prognostic factor for overall survival (Log-rank: p=0.0453), whereas Cox multivariate analysis identified extracapsular spread as an independent prognostics marker (p=0.049; hazard ratio 1.86 [95% confidence interval 1.00-3.43]). We conclude that the presented multimodal approach of surgery for the primary tumor and the neck followed by postoperative radio(chemo)therapy seems to be superior to non-surgical treatment protocols, as it results in better disease-free and overall survival. To assess this multimodal treatment approach, morbidity and economic considerations need to be further analyzed.

An analysis of surgical complications, morbidity, and cost calculation in patients undergoing multimodal treatment for operable oropharyngeal carcinoma.

OBJECTIVE/HYPOTHESIS: Tumor control and survival are considered the most important measures of treatment efficacy for patients with primary oropharyngeal squamous cell carcinoma. Furthermore, multimodal treatment protocols should be judged by their complication rates, morbidity, and therapy costs. STUDY DESIGN: The results of a combined approach of primary surgery and neck dissection with postoperative radio(chemo)therapy were analyzed in retrospective chart review. METHODS: Two hundred eleven patients' records were analyzed for surgical complications, therapeutic morbidity, and treatment costs. RESULTS: The rate of postoperative hemorrhage was 4.7%. We observed no fatal complications. Ten percent of our patients required nutrition through percutaneous endoscopic gastrostomy (PEG). Twelve percent of all patients required long-term tracheostomy. The rates of PEG and tracheostomy were significantly higher in patients operated by the transcervical approach. The costs for the combined approach ranged from 10,587 euros (13,377 dollars) to 24,531 euros (30,996 dollars). CONCLUSIONS: The presented multimodal approach provides a low rate of surgical complications and a tolerable morbidity. Considering the excellent oncologic results, this extensive and more cost-intensive multimodal approach is justified for patients with oropharyngeal cancer.

The Role of Radiotherapy in the Definitive and Postoperative Treatment of Advanced Head and Neck Cancer.

Radiotherapy plays an important role in the treatment of head and neck cancer. It represents the main curative option in advanced tumors. Due to technical progress of treatment appliances, the translation of radiobiological research into clinical praxis (altered fractionation), and the concurrent application of chemotherapy (radiochemotherapy), the efficacy of radiotherapy has markedly improved. Current developments focus on the integration of functional imaging into the treatment planning process to allow individualized dose prescription. Different systemic agents have shown to improve prognosis when applied concurrently with radiotherapy, whereas induction chemotherapy has not proven to be of further benefit. Treatment of human papillomavirus-related oropharyngeal carcinomas is challenging. Reduced treatment intensity for this entity is being investigated but cannot be recommended for clinical routine at this point. Adjuvant radiotherapy and radiochemotherapy improve the prognosis in high-risk head and neck cancer after surgical treatment. Further reductions in the treated neck volume in adjuvant radiotherapy need clinical investigation.

Robot-assisted Extracranial Stereotactic Radiotherapy of Adrenal Metastases in Oligometastatic Non-small Cell Lung Cancer.

AIM: The aim of this study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in the treatment of patients with adrenal metastases in oligometastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between November 2012 and May 2015, fifteen patients with oligometastatic non-small cell lung cancer and adrenal metastases were treated with the Cyberknife® system. The primary endpoint was local control. RESULTS: The 1-year and 2-year local control rates were 60% and 46.6%, respectively. The differences in local control for patients with metachronous and synchronous metastases reached statistical significance (p=0.00028). Two-year overall survival of 91.2% for patients with metachronous metastases was also more favourable compared to patients with synchronous adrenal metastases with 42.8%. CONCLUSION: Extracranial stereotactic radiotherapy with the Cyberknife® is a safe and non-invasive technique that extends the therapeutic spectrum in the treatment of patients with adrenal metastases in oligometastatic NSCLC.

Short review of potential synergies of immune checkpoint inhibition and radiotherapy with a focus on Hodgkin lymphoma: radio-immunotherapy opens new doors.

Radiotherapy is an established local treatment in patients with various malignancies. Systemic responses following local irradiation have been described as abscopal effects. Modern cancer immunotherapy with immune checkpoint inhibitors has shown impressive response rates and prolongation of survival even in heavily pretreated patients with advanced solid malignancies and lymphomas. Radiotherapy has been shown to modulate immune response, and its application in the context of immune checkpoint inhibition has recently evolved into an active field of research. Prospective studies investigating combination treatment are currently ongoing and will answer questions as to the optimal schedule and radiation dosing. This short review focuses on the immunomodulatory role of radiotherapy and the use of immune checkpoint inhibition with a special focus on Hodgkin lymphoma.

Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer.

PURPOSE: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. PATIENTS AND METHODS: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. RESULTS: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. CONCLUSIONS: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.

Diagnostic work-up and outcome of cervical metastases from an unknown primary.

CONCLUSIONS: An intensive diagnostic work-up including (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) detects many unknown primary tumours, leads to a low emergence rate of primary tumours, and selects carcinoma of unknown primary with much more favourable results after neck dissection and postoperative radiotherapy. OBJECTIVE: To investigate the optimal diagnostic approach and best treatment modality for rare head and neck cancer of unknown primary. PATIENTS AND METHODS: In a retrospective study, 69 patients admitted from 1987 to 2002 with cervical lymph node metastases without apparent primary were reviewed. Test characteristics of all diagnostic procedures were calculated. Disease-free and overall survival rates were calculated. Major prognostic factors were analysed uni-variously. RESULTS: At the primary site FDG-PET showed the best sensitivity with 69% and the highest negative predictive value with 87%. Computed tomography and magnetic resonance imaging had a better specificity with 87% and 95%, respectively. The primary tumour was detected in 23 cases (33%). Frequent primary tumour origin was the palatine tonsil (n=8, 35%), base of the tongue (n=6, 26%) and lung (n=4, 17%). All patients with unknown primary were treated by neck dissection. Adjuvant radiotherapy was performed in 26 patients (57%), concurrent radiochemotherapy was performed in 12 patients (26%). The primary emergence rate was 7%. The 5-year overall survival rate was inferior in patients with detected primary in comparison with patients with unknown primary (22% versus 52%). Significant prognostic factors in case of unknown primary were M stage, smoking, alcohol consumption and tonsillectomy. Radiotherapy but not chemotherapy with carboplatin influenced the overall survival.

Initiation of a teleradiotherapeutic network for patients in German lymphoma studies.

PURPOSE: Deviations of radiation treatment portals and dose from prospective treatment plans are unfavorable prognostic factors for lymphoma patients. Therefore, an extensive radiotherapy quality assurance program is used in the ongoing German lymphoma studies. The introduction of teleradiotherapy offered the opportunity to optimize and simplify the workflow of these quality assurance programs. The purpose of this report was to evaluate the feasibility of teleradiotherapy and to describe our experiences with these innovative tools. METHODS AND MATERIALS: During this pilot phase, five radiotherapy centers were equipped with the hardware and software that guarantees a rapid and high-quality transfer of imaging data, as well as real-time teleconferences. The workstation consists of standard PCs with Windows NT as the operating system and the commercial telemedicine software Hipax. RESULTS: As a first step, imaging communication between the radiotherapy reference centers in Cologne and Homburg/Saar was established. Subsequently, three additional radiotherapy departments (Universities of Berlin, Münster, and Munich) with large numbers of lymphoma patients were connected. Other study centers delivered digital imaging on mobile data carriers or via an Integrated Services Digital Network point-to-point connection. Communication units were completed for interactive teleconferences. A facility for central online documentation was installed. Telemedical functions were integrated into the ongoing radiotherapy quality assurance program. Since the introduction of a teleradiotherapeutic workstation in the radiotherapy reference center in Cologne in January 2001, the images of 10% (n = 228 patients) of all reviewed cases of the ongoing Hodgkin's disease 10-12 trials were delivered digitally. The amount of digitally available imaging is continuously increasing. CONCLUSION: The introduction of teleradiotherapy improved the dialog between the radiotherapy reference centers and study centers and thus contributed toward high radiotherapy quality for lymphoma patients in Germany.