Catalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy.

Nanoparticle-based radioenhancement is a promising strategy for extending the therapeutic ratio of radiotherapy. While (pre)clinical results are encouraging, sound mechanistic understanding of nanoparticle radioenhancement, especially the effects of nanomaterial selection and irradiation conditions, has yet to be achieved. Here, we investigate the radioenhancement mechanisms of selected metal oxide nanomaterials (including SiO2, TiO2, WO3 and HfO2), TiN and Au nanoparticles for radiotherapy utilizing photons (150 kVp and 6 MV) and 100 MeV protons. While Au nanoparticles show outstanding radioenhancement properties in kV irradiation settings, where the photoelectric effect is dominant, these properties are attenuated to baseline levels for clinically more relevant irradiation with MV photons and protons. In contrast, HfO2 nanoparticles retain some of their radioenhancement properties in MV photon and proton therapies. Interestingly, TiO2 nanoparticles, which have a comparatively low effective atomic number, show significant radioenhancement efficacies in all three irradiation settings, which can be attributed to the strong radiocatalytic activity of TiO2, leading to the formation of hydroxyl radicals, and nuclear interactions with protons. Taken together, our data enable the extraction of general design criteria for nanoparticle radioenhancers for different treatment modalities, paving the way to performance-optimized nanotherapeutics for precision radiotherapy.

Role of Adjuvant Radiotherapy in Non-Small Cell Lung Cancer-A Review.

BACKGROUND: For patients with completely resected non-small cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (pN2), the administration of adjuvant chemotherapy is the standard of care. The role of postoperative radiation therapy (PORT) is controversial. METHODS: We describe the current literature focusing on the role of PORT in completely resected NSCLC patients with pN2 involvement and reflect on its role in current guidelines. RESULTS: Based on the results of the recent Lung ART and PORT-C trials, the authors conclude that PORT cannot be generally recommended for all resected pN2 NSCLC patients. A substantial decrease in the locoregional relapse rate without translating into a survival benefit suggests that some patients with risk factors might benefit from PORT. This must be balanced against the risk of cardiopulmonary toxicity with potentially associated mortality. Lung ART has already changed the decision making for the use of PORT in daily practice for many European lung cancer experts, with lower rates of recommendations for PORT overall. CONCLUSIONS: PORT is still used, albeit decreasingly, for completely resected NSCLC with pN2 involvement. High-level evidence for its routine use is lacking. Further analyses are required to identify patients who would potentially benefit from PORT.

Role of Brachytherapy in the Postoperative Management of Endometrial Cancer: Decision-Making Analysis among Experienced European Radiation Oncologists.

BACKGROUND: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. METHODS: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. RESULTS: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1-2 LVSI-negative disease. For 74-84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. CONCLUSIONS: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1-2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.

Radiotherapy or Surgery? Comparative, Qualitative Assessment of Online Patient Education Materials on Prostate Cancer.

As multiple different treatment options are available for prostate cancer (PCa) and YouTube is commonly used as a source for medical information, we performed a systematic and comparative assessment of available videos guiding patients on their choice for the optimal treatment. An independent search for surgical therapy or radiotherapy of PCa on YouTube was performed and the 40 most viewed videos of both groups were analyzed. The validated DISCERN questionnaire and PEMAT were utilized to evaluate their quality and misinformation. The median overall quality of the videos was found to be low for surgery videos, while radiotherapy videos results reached a moderate quality. The median PEMAT understandability score was 60% (range 0-100%) for radiotherapy and 75% (range 40-100) for surgery videos. The radiotherapy videos contained less misinformation and were judged to be of higher quality. Summarized, the majority of the provided videos offer insufficient quality of content and are potentially subject to commercial bias without reports on possible conflict of interest. Thus, most of available videos on YouTube informing PCa patients about possible treatment methods are not suited for a balanced patient education or as a basis for the patient's decision.

Dose-intensified Versus Conventional-dose Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: The SAKK 09/10 Randomized Phase 3 Trial.

BACKGROUND: Salvage radiotherapy (SRT) is utilized for biochemical progression of prostate cancer after radical prostatectomy (RP). OBJECTIVE: To report the outcomes of the SAKK 09/10 trial comparing conventional and dose-intensified SRT. DESIGN, SETTING, AND PARTICIPANTS: SAKK 09/10 was a randomized, multicenter, phase 3 trial that recruited men with biochemical progression after RP. INTERVENTION: Patients were randomly assigned to conventional-dose (64 Gy) or dose-intensified SRT (70 Gy) to the prostate bed without hormonal therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was freedom from biochemical progression (FFBP). Secondary endpoints included clinical progression-free survival (PFS), time to hormonal treatment, overall survival (OS), acute and late toxicity (Common Terminology Criteria for Adverse Events v4.0), and quality of life (QoL). RESULTS AND LIMITATIONS: Between February 2011 and April 2014, 350 patients were randomly assigned to 64 Gy (n = 175) or 70 Gy (n = 175). Median prostate-specific antigen at randomization was 0.3 ng/ml. After median follow-up of 6.2 yr, the median FFBP was 8.2 yr in the 64 Gy arm and 7.6 in the 70 Gy arm (log-rank p = 0.4), with a hazard ratio of 1.14 (95% confidence interval 0.82-1.60). The 6-year FFBP rates were 62% and 61%, respectively. No significant differences in clinical PFS, time to hormonal treatment, or OS were observed. Late grade 2 and 3 genitourinary toxicity was observed in 35 (21%) and 13 (7.9%) patients in the 64 Gy arm, and 46 (26%) and seven (4%) in the 70 Gy arm, respectively (p = 0.8). Late grade 2 and 3 gastrointestinal toxicity was observed in 12 (7.3%) and seven patients (4.2%) in the 64 Gy arm, and 35 (20%) and four (2.3%) in the 70 Gy arm, respectively (p = 0.009). There were no significant differences in QoL. CONCLUSIONS: Conventional-dose SRT to the prostate bed is sufficient in patients with early biochemical progression of prostate cancer after RP. PATIENT SUMMARY: The optimal radiation therapy dose for patients who have increased tumor markers after surgery for prostate cancer is unclear. We found that administering a higher dose only increased the gastrointestinal side effects without providing any benefits to the patient. This clinical trial is registered on ClinicalTrials.gov as NCT01272050.

Radiotherapy for lentigo maligna and lentigo maligna melanoma - a systematic review.

Lentigo maligna (LM) is the most common subtype of in situ melanoma und occurs frequently in the sun-exposed head and neck region in elderly patients. The therapeutic "gold standard" is surgical excision, as there is the risk of progression to invasive (lentigo maligna) melanoma (LMM). However, surgery is not feasible in certain patients due to age, comorbidities or patient preference. Radiotherapy using Grenz rays or superficial X-rays has been established as non-invasive alternative for the treatment of LM and LMM. We performed a systematic literature search of MEDLINE and Embase databases in September 2019 and identified 14 patient series using radiotherapy for LM or LMM. No prospective trials were found. The 14 studies reported a total of 1243 lesions (1075 LM and 168 LMM) treated with radiotherapy. Local recurrence rates ranged from 0 to 31% and were comparable to surgical series in most of the reports on radiotherapy. Superficial radiotherapy was prescribed in 5-23 fractions with a total dose of 35-57 Gy. Grenz ray therapy was prescribed in 42-160 Gy in 3-13 fractions with single doses up to 20 Gy. Cosmetic results were reported as "good" to "excellent" for the majority of patients.In conclusion, the available low-level evidence suggests that radiotherapy may be a safe and effective treatment for LM and LMM. Data from prospective trials such as the phase 3 RADICAL trial are needed to confirm these promising findings and to compare radiotherapy to other non-surgical therapies and to surgery.

Insular Decision Criteria in Clinical Practice: Analysis of Decision-Making in Oncology.

BACKGROUND: Medical decision-making is complex and involves a variety of decision criteria, many of which are universally recognised. However, decision-making analyses have demonstrated that certain decision criteria are not used uniformly among clinicians. AIM: We describe decision criteria, which for various contexts are only used by a minority of decision makers. For these, we introduce and define the term "insular criteria". METHODS: 19 studies analysing clinical decision-making based on decision trees were included in our study. All studies were screened for decision-making criteria that were mentioned by less than three local decision makers in studies involving 8-26 participants. RESULTS: 14 out of the 19 included studies reported insular criteria. We identified 42 individual insular criteria. They could be intuitively allocated to seven major groups, these were: comorbidities, treatment, patients' characteristics/preferences, caretaker, scores, laboratory and tumour properties/staging. CONCLUSION: Insular criteria are commonly used in clinical decision-making, yet, the individual decision makers may not be aware of them. With this analysis, we demonstrate the existence of insular criteria and their variety. In daily practice and clinical studies, awareness of insular criteria is important.

Long-term oncological and functional follow-up in low-dose-rate brachytherapy for prostate cancer: results from the prospective nationwide Swiss registry.

OBJECTIVE: To evaluate the long-term oncological, functional and toxicity outcomes of low-dose-rate brachytherapy (LDR-BT) in relation to risk factors and radiation dose in a prospective multicentre cohort. PATIENTS AND METHODS: Data of patients from 12 Swiss centres undergoing LDR-BT from September 2004 to March 2018 were prospectively collected. Patients with a follow-up of ≥3 months were analysed. Functional and oncological outcomes were assessed at ~6 weeks, 6 and 12 months after implantation and annually thereafter. LDR-BT was performed with 125 I seeds. Dosimetry was done 6 weeks after implantation based on the European Society for Radiotherapy and Oncology recommendations. The Kaplan-Meier method was used for biochemical recurrence-free survival (BRFS). A prostate-specific antigen (PSA) rise above the PSA nadir + 2 was defined as biochemical failure. Functional outcomes were assessed by urodynamic measurement parameters and questionnaires. RESULTS: Of 1580 patients in the database, 1291 (81.7%) were evaluable for therapy outcome. The median (range) follow-up was 37.1 (3.0-141.6) months. Better BRFS was found for Gleason score ≤3+4 (P = 0.03, log-rank test) and initial PSA level of <10 ng/mL (P < 0.001). D'Amico Risk groups were significantly associated with BRFS (P < 0.001), with a hazard ratio of 2.38 for intermediate- and high-risk patients vs low-risk patients. The radiation dose covering 90% of the prostate volume (D90) after 6 weeks was significantly lower in patients with recurrence. Functional outcomes returned close to baseline levels after 2-3 years. A major limitation of these findings is a substantial loss to follow-up. CONCLUSION: Our results are in line with other studies showing that LDR-BT is associated with good oncological outcomes together with good functional results.

[Modern Treatment Concepts in Radiation Oncology]. / Moderne Behandlungskonzepte in der Radio-Onkologie.

Modern Treatment Concepts in Radiation Oncology Abstract. Radiotherapy is a widely used form of therapy that is used in half of all cancer patients. Advances in understanding the fundamentals of tumor and radiation biology, in medical physics and computer science as well as technical developments have continuously improved the effectiveness and healing success of radiotherapy. Patients benefit from new treatment concepts such as hypofractionated radiotherapy for breast and prostate cancer, leading to a reduction in the duration of treatment by several weeks. Selected patients with early stages of breast cancer can be treated with partial breast irradiation with focus on the tumor bed after breast conserving surgery increasing tolerability and comfort. High dose stereotactic radiotherapy over five to six sessions of radiation or only one fraction (radiosurgery) have expanded treatment options for common tumor entities leading to long-lasting tumor control resulting in improved survival and quality of life for those affected. In early lung cancer stereotactic radiotherapy is an alternative to primary tumor surgery. For patients with oligometastatic tumor disease stereotactic radiotherapy allows a curative approach by effectively treating metastases. In patients with brain metastases whole-brain irradiation is replaced by stereotactic irradiation of the individual metastases with fewer side effects. Recently, promising results for improved tumor control with the combination of radiotherapy and immunotherapy have been presented. Radioimmunotherapy represents a new therapy combination. However, final assessment of its efficacy and side effects profile is still missing. In order to gain therapeutic certainty, further prospective study data are necessary.

Skeletal muscle mass correlates with increased toxicity during neoadjuvant radiochemotherapy in locally advanced esophageal cancer: A SAKK 75/08 substudy.

BACKGROUND: Sarcopenia, the critical depletion of skeletal muscle mass, is an independent prognostic factor in several tumor entities for treatment-related toxicity and survival. In esophageal cancer, there have been conflicting results regarding the value of sarcopenia as prognostic factor, which may be attributed to the heterogeneous patient populations and the retrospective nature of previous studies. The aim of our study was therefore to determine the impact of sarcopenia on prospectively collected specific outcomes in a subgroup of patients treated within the phase III study SAKK 75/08 with trimodality therapy (induction chemotherapy, radiochemotherapy and surgery) for locally advanced esophageal cancer. METHODS: Sarcopenia was assessed by skeletal muscle index at the 3rd lumbar vertebra (L3) in cross-sectional computed tomography scans before induction chemotherapy, before radiochemotherapy and after neoadjuvant therapy in a subgroup of 61 patients from four centers in Switzerland. Sarcopenia was determined by previously established cut-off values (Martin et al., PMID: 23530101) and correlated with prospectively collected outcomes including treatment-related toxicity, postoperative morbidity, treatment feasibility and survival. RESULTS: Using the published cut-off values, the prevalence of sarcopenia increased from 29.5% before treatment to 63.9% during neoadjuvant therapy (p < 0.001). Feasibility of neoadjuvant therapy and surgery was not different in initially sarcopenic and non-sarcopenic patients. We observed in sarcopenic patients significantly increased grade ≥ 3 toxicities during chemoradiation (83.3% vs 52.4%, p = 0.04) and a non-significant trend towards increased postoperative complications (66.7% vs 42.9%, p = 0.16). No difference in survival according to sarcopenia could be observed in this small study population. CONCLUSIONS: Trimodality therapy in locally advanced esophageal cancer is feasible in selected patients with sarcopenia. Neoadjuvant chemoradiation increased the percentage of sarcopenia. Sarcopenic patients are at higher risk for increased toxicity during neoadjuvant radiochemotherapy and showed a non-significant trend to more postoperative morbidity.

Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial.

Postoperative radiotherapy after extrapleural pneumonectomy of malignant pleural mesothelioma was investigated in the randomized phase II trial SAKK17/04. The relapse rate within the high and/or low-dose PTV without previous distant failure was 24%, the isolated in-field-relapse rate within the PTVs was 5% and the distant relapse rate outside of the PTVs was 81%. Clinical outcome was mainly determined by distant disease progression outside of the radiation field.

A cost-effectiveness analysis of consolidative local therapy in oligometastatic non-squamous non-small cell lung cancer (NSCLC).

BACKGROUND: Novel systemic therapies have improved the prognosis of metastatic non-small cell lung cancer (NSCLC), but costs of some of these drugs are a matter of ongoing debate. More recently, local therapies (LT) such as radiotherapy and surgery have been suggested as additional treatment in oligometastatic NSCLC demonstrating an improved progression-free survival (PFS) in a phase II trial compared to maintenance chemotherapy (MC) alone. The aim of this analysis was to assess the cost-effectiveness of local therapies in oligometastatic NSCLC. METHODS: We constructed a Markov model comparing the cost-effectiveness of LT versus MC for oligometastatic NSCLC from the Swiss healthcare payer's perspective. Treatment specifications and PFS were based on the phase II trial (NCT01725165). Overall survival (OS) was inferred from a recent phase III trial. Utilities were taken from published data. Primary outcome was the incremental cost-effectiveness-ratio (ICER, costs in Swiss Francs (CHF) per quality-adjusted life-year (QALY) gained). RESULTS: PFS in the model was 3.8 months for MC and 11.4 months for LT (compared to 3.9 months and 11.9 months in the trial). OS in the model was 15.5 months in both arms. LT was cost-effective with a gain of 0.24 QALYs at an additional cost of CHF 9641, resulting in an ICER of CHF 40,972/QALY gained. Probabilistic sensitivity analyses demonstrated that LT was dominant or cost-effective at a willingness-to-pay threshold of CHF 100,000 per QALY in 61.7% of the simulations. CONCLUSIONS: LT may be cost-effective for selected patients with oligometastatic NSCLC responding to first-line systemic therapy.

Late seed migration after prostate brachytherapy with Iod-125 permanent implants.

BACKGROUND: Seed migration is a common finding after low dose rate brachytherapy of the prostate. It has often been assessed soon after implantation, but little is known about late seed migration. We evaluated the incidence, site, symptoms, and therapeutic consequences of late seed migration more than 3 years postoperatively. MATERIALS AND METHODS: We retrospectively examined the data of 63 unselected patients with transrectal ultrasound-guided, transperineal low dose rate brachytherapy of the prostate with stranded seeds between 2001 and 2010. A pelvic X-ray was taken the day after implantation and after 6 weeks in combination with a pelvic computed tomography/magnetic resonance imaging scan (image fusion) for dosimetry. Late radiological follow-up with a further pelvic and chest X-ray was conducted 3 or more years postoperatively. We differed between seed loss without anatomical detection and seed migration into another anatomical region. RESULTS: We found seed loss up to 3 years and more after brachytherapy in 36 of 63 patients (57%). Between one and nine seeds had been lost. Late seed migration after 3 or more years occurred in two of 36 patients (6%), with pelvic migration of one seed and extrapelvic migration of one seed to the lung and two seeds to the liver, respectively. All late seed migrations were asymptomatic and had no therapeutic consequences. CONCLUSION: Beside a frequent number of seed losses, seed migration 3 or more years after implantation was as well a frequent finding but seems to be asymptomatic. Long-term follow-up with complementary radiological controls could be helpful in detecting any rare complications.

Treatment Options in Oncology.

Multiple treatment strategies exist for many oncologic problems. In this review, we provide a summary of various reasons for the existence of multiple treatment options in oncology, including factors that concern the treating physician (eg, treatment preferences), environmental factors (eg, financial, regulatory, and scientific aspects), and individual patient-specific factors (eg, medical condition, preferences). We demonstrate the vital role of available treatment options and their origins for clinical decision making and patient communication. These aspects are particularly helpful in the process of shared decision making, which is increasingly favored in situations where there are multiple medically reasonable options.

Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08).

BACKGROUND: KRAS mutation occurs in ∼40% of locally advanced rectal cancers (LARCs). The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for standard preoperative chemoradiotherapy in patients with KRAS-mutated LARC. METHODS: Adult patients with KRAS-mutated T3/4 and/or N1/2M0 LARC were included in this phase I/II study. The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety. Primary end-points were to: establish the maximum tolerated dose of the regimen in phase I; determine the pathologic complete response (pCR) rate in phase II defined as Dworak regression grade 3 and 4. RESULTS: Fifty-four patients were treated at 18 centres in Switzerland and Hungary; 40 patients were included in the single-arm phase II study. Recommended doses from phase I comprised radiotherapy (45 Gy in 25 fractions over 5 weeks) with capecitabine 825 mg/m2 twice daily × 33 plus sorafenib 400 mg/d. Median daily dose intensity in phase II was radiotherapy 100%, capecitabine 98.6%, and sorafenib 100%. The pCR rate (Dworak 3/4) was 60% (95% CI, 43.3-75.1%) by central independent pathologic review. Sphincter preservation was achieved in 89.5%, R0 resection in 94.7%, and downstaging in 81.6%. The most common grade 3 toxicities during phase II included diarrhoea (15.0%), skin toxicity outside radiotherapy field (12.5%), pain (7.5%), skin toxicity in radiotherapy field, proctitis, fatigue and cardiac ischaemia (each 5%). CONCLUSIONS: Combining sorafenib and standard chemoradiotherapy with capecitabine is highly active in patients with KRAS-mutated LARC with acceptable toxicity and deserves further investigation. www.clinicaltrials.gov: NCT00869570.

Applied Swarm-based medicine: collecting decision trees for patterns of algorithms analysis.

BACKGROUND: The objective consensus methodology has recently been applied in consensus finding in several studies on medical decision-making among clinical experts or guidelines. The main advantages of this method are an automated analysis and comparison of treatment algorithms of the participating centers which can be performed anonymously. METHODS: Based on the experience from completed consensus analyses, the main steps for the successful implementation of the objective consensus methodology were identified and discussed among the main investigators. RESULTS: The following steps for the successful collection and conversion of decision trees were identified and defined in detail: problem definition, population selection, draft input collection, tree conversion, criteria adaptation, problem re-evaluation, results distribution and refinement, tree finalisation, and analysis. CONCLUSION: This manuscript provides information on the main steps for successful collection of decision trees and summarizes important aspects at each point of the analysis.

Secondary malignancies after rectal cancer resection with and without radiation therapy: A propensity-adjusted, population-based SEER analysis.

BACKGROUND: The relationship between radiation therapy for rectal cancer and secondary malignancies is debated. The present study is the first population-based analysis using conventional multivariable analyses as well as propensity score matching to assess this relationship. METHODS: Overall, 77,484 patients after resection of localized or locally advanced rectal adenocarcinoma diagnosed between 1973 and 2012 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. The occurrence of secondary malignancies diagnosed at least 1 (median follow up 5.8years [1-39.9years]) year after rectal cancer diagnosis was compared in patients who did and did not undergo radiation using stratified and propensity score matched Cox regression analysis. RESULTS: Of 77,484 patients, 34,114 underwent radiation and 43,370 did not. Ignoring gender and entity, radiation therapy was not associated with secondary malignancies (hazard ratio [HR]=0.97 (95%CI: 0.92-1.02, P=0.269). The risk for prostate cancer was decreased and (HR=0.42, 95%CI: 0.36-0.48, P<0.001) and increased risk for endometrial cancer (HR=1.95, 95%CI: 1.49-2.56, P<0.001). Overall, patients undergoing radiation had higher risks for lung cancer (HR=1.18, 95%CI: 1.06-1.30, P<0.001), bladder cancer (HR=1.54, 95%CI: 1.31-1.80, P<0.001) and lymphomas (HR=1.27, 95%CI: 1.03-1.58, P=0.026). CONCLUSIONS: The present analysis describes the occurence of secondary malignancies after pelvic radiation in patients undergoing rectal cancer surgery. Indeed, radiation for rectal cancer is associated with a significantly decreased risk of prostate cancer, however, an increased risk of endometrial, lung, and bladder cancer as well as lymphomas was observed. Overall, the risk of secondary malignancies was slightly decreased with radiation in patients undergoing rectal cancer resection, this was attributable to lower rates in prostate cancer.

Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers : Secondary results of two European randomized phase III trials (ARO 95-06, SAKK 10/94).

BACKGROUND: To determine the influence of baseline laboratory values on treatment outcome in patients with locally advanced head and neck cancer (HNSCC). METHODS: Data of the randomized trials ARO 95 -06 (n = 384) and SAKK 10 /94 (n = 224) were pooled for a total sample size of 608 patients. Haemoglobin (Hb) and creatinine (Cr) were available at baseline and their association with locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using univariable and multivariable Cox regression models. RESULTS: A total of 580 and 564 patients were available with baseline Hb and Cr values in the pooled analysis. Univariable analyses revealed that lower baseline Hb values were significantly associated with decreased LRRFS, DMFS, CSS and OS. This effect remained significant for OS when the treatment arms (radiotherapy [RT] alone vs. chemoradiation [CRT]) were analyzed separately. Higher baseline Cr was associated with improved OS in the pooled analysis. Interestingly, the prognostic value of baseline Cr appeared to be limited to the subgroup of 284 patients who were treated with CRT. In the multivariable Cox regression model lower baseline Hb remained associated with decreased OS both in the patients who received CRT (HR 0.79, 95 % CI 0.66-0.94, p = 0.009) and in those patients who underwent RT alone (HR 0.67, 95 % CI 0.58-0.78, p < 0.001). Increased baseline Cr remained significantly associated with improved OS in patients who underwent CRT (HR 0.79, 95 % CI 0.69-0.92, p = 0.002) but not in those patients who underwent RT alone. CONCLUSIONS: An association between lower baseline Hb and inferior treatment outcome was confirmed. Baseline Cr was introduced as a prognosticator of outcome after CRT for locally advanced HNSCC.

Volumetric regression ratio of the primary tumor and metastatic lymph nodes after induction chemotherapy predicts overall survival in head and neck squamous cell carcinoma: a retrospective analysis.

PURPOSE: We looked for any predictive value of change in primary tumor and metastatic lymph node volumes after induction chemotherapy (IC) on oncologic outcome in head and neck squamous cell carcinoma (HNSCC). METHODS: Nineteen patients with stage IVA/B HNSCC treated between 2004 and 2010 with at least one cycle of IC (docetaxel, cisplatin and 5-fluorouracil/TPF) and concomitant chemoradiotherapy (CRT) with cisplatin were retrospectively analyzed. Volumes were calculated separately for primary tumor (Vtm), lymph node metastases (Vln) and their sum (Vsum) on computed tomography (CT) images before and after IC. The effect of volumetric changes on locoregional failure (LRF), distant metastasis (DM) and overall survival (OS) was assessed. P values <0.05 were considered as statistically significant. RESULTS: The median follow-up of surviving patients was 25 months (range: 10.7-83.3). The median number of cycles and duration of TPF was 3 (range: 1-4) and 44 days (range: 4-116), respectively. Empirical area under the curve (AUC) analyses for death, LRF and DM revealed optimal cut-off values of Vtm diminution (30.54%, AUC: 87%) and Vsum decrease (35.45%, AUC: 64.55%) only for OS (p <0.05). Among those, a reduction in Vsum more than 35.4% between pre- and post-IC was significantly correlated with better OS (100 vs 43% at 2 years, p <0.05). CONCLUSION: Volumetric shrinkage of the tumor load after IC assessed with CT seems to predict OS. The assessment of volumetric shrinkage upon IC might be used to decide whether to offer patients alternative strategies like palliative/de-intensified treatments or more aggressive combined modalities after IC.

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10.

PURPOSE: Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS: Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS: Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION: Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.