Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study.

Purpose: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium.

Patients And Methods: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m days 1, 8, and 15; cisplatin 70 mg/m day 2) or standard MVAC every 28 days for a maximum of six cycles.

Results: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202).

Expanded HILUS Trial: A Pooled Analysis of Risk Factors for Toxicity From Stereotactic Body Radiation Therapy of Central and Ultracentral Lung Tumors.

Purpose: Stereotactic body radiation therapy for tumors near the central airways implies high-grade toxic effects, as concluded from the HILUS trial. However, the small sample size and relatively few events limited the statistical power of the study. We therefore pooled data from the prospective HILUS trial with retrospective data from patients in the Nordic countries treated outside the prospective study to evaluate toxicity and risk factors for high-grade toxic effects.

Predicting the benefit of stereotactic body radiotherapy of colorectal cancer metastases.

Aim: To evaluate Stereotactic body radiotherapy (SBRT) in metastatic colorectal cancer (mCRC) and identify the benefit of the treatment by using a predictive algorithm.

Methods: 85 patients treated with SBRT for mCRC were retrospectively analyzed. The CLInical Categorical Algorithm (CLICAL©) was used to predict probability of relapse after SBRT.

Estimation of delivered dose to lung tumours considering setup uncertainties and breathing motion in a cohort of patients treated with stereotactic body radiation therapy.

Introduction: Dose-response relationships for local control of lung tumours treated with stereotactic body radiotherapy (SBRT) have proved ambiguous, however, these have been based on the prescribed or planned dose. Delivered dose to the target may be a better predictor for local control. In this study, the probability of the delivered minimum dose to the clinical target volume (CTV) in relation to the prescribed dose was estimated for a cohort of patients, considering geometrical uncertainties.

The HILUS-Trial-a Prospective Nordic Multicenter Phase 2 Study of Ultracentral Lung Tumors Treated With Stereotactic Body Radiotherapy.

Introduction: Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity.

Methods: Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume.

Extending hypofractionated stereotactic body radiotherapy to tumours larger than 70cc - effects and side effects.

Background And Purpose: Stereotactic body radiotherapy (SBRT) for tumours ≥5 cm is poorly studied and its utility and feasibility is uncertain. We here report the Karolinska experience of SBRT in this setting.

Material And Methods: All patients had a gross tumour volume (GTV) ≥70 cc, a prescribed physical dose of at least 40 Gy and received treatment between 1995-2012.

Metastatic renal cell carcinoma to the brain: optimizing patient selection for gamma knife radiosurgery.

Introduction: The effects of single-fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA) and immune checkpoint inhibitors (ICI) are insufficiently studied.

Methods And Materials: Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n = 43). Median follow-up was 56 months.

Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer.

Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depend on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy.

Adaptive radiosurgery based on two simultaneous dose prescriptions in the management of large renal cell carcinoma brain metastases in critical areas: Towards customization.

Background: The long-term benefits of local therapy in metastatic renal cell carcinoma (mRCC) have been widely documented. In this context, single fraction gamma knife radiosurgery (SF-GKRS) is routinely used in the management of brain metastases. However, SF-GKRS is not always feasible due to volumetric and regional constraints.

Radiation-induced brachial plexus toxicity after SBRT of apically located lung lesions.

: To evaluate the rate and dose response of brachial plexus toxicity post stereotactic body radiation therapy (SBRT) of apically situated lung lesions. We retrospectively identified all patients with apically located tumors, defined by the epicenter of the tumor being located superiorly to the aortic arch, and treated with SBRT between 2008 and 2013. Patients with a shorter follow-up than 6 months were excluded.

Impact of SBRT fractionation in hypoxia dose painting - Accounting for heterogeneous and dynamic tumor oxygenation.

Purpose: Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on F-HX4 positron emission tomography (PET) imaging of NSCLC.

Low Infection Rate After Transrectal Implantation of Gold Anchor ™ Fiducial Markers in Prostate Cancer Patients After Non-broad-spectrum Antibiotic Prophylaxis.

Background In 621 consecutive prostate cancer patients, the frequency of urinary tract infections (UTI) and marker loss was evaluated. They prophylactically received a single dose of non-broad-spectrum antibiotics and transrectal implantation of three thin needle fiducial markers, Gold Anchor ™ (GA). Methods The occurrence of UTIs, sepsis, hospitalization due to infection, and marker loss after implantation was assessed from the medical records containing notes from physicians and nurses from the day of implantation to the end of 29 fractions.

Overall survival after stereotactic radiotherapy or surgical metastasectomy in oligometastatic renal cell carcinoma patients treated at two Swedish centres 2005-2014.

Background And Purpose: Investigate effects of stereotactic radiotherapy (SRT) or surgical metastasectomy (SM) on overall survival (OS) in metastatic renal cell carcinoma (mRCC) in the era of targeted agents (TA).

Material And Methods: mRCC patients (n = 117) treated with SRT (n = 57), SM (n = 30) or both modalities sequentially (n = 30) at two oncological centres in Sweden in 2005-2014 were retrospectively included. Median follow-up (mFU) was 63 months.

Evaluation of third treatment week as temporal window for assessing responsiveness on repeated FDG-PET-CT scans in Non-Small Cell Lung Cancer patients.

Purpose: Early assessment of tumour response to treatment with repeated FDG-PET-CT imaging has potential for treatment adaptation but it is unclear what the optimal time window for this evaluation is. Previous studies indicate that changes in SUV and the effective radiosensitivity (α, accounting for uptake variations and accumulated dose until the second FDG-PET-CT scan) are predictive of 2-year overall survival (OS) when imaging is performed before radiotherapy and during the second week. This study aims to investigate if multiple FDG-PET-derived quantities determined during the third treatment week have stronger predictive power.

Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription.

Background: Tumour hypoxia is associated with increased radioresistance and poor response to radiotherapy. Pre-treatment assessment of tumour oxygenation could therefore give the possibility to tailor the treatment by calculating the required boost dose needed to overcome the increased radioresistance in hypoxic tumours. This study concerned the derivation of a non-linear conversion function between the uptake of the hypoxia-PET tracer F-HX4 and oxygen partial pressure (pO).

Defining the hypoxic target volume based on positron emission tomography for image guided radiotherapy - the influence of the choice of the reference region and conversion function.

Background: Hypoxia imaged by positron emission tomography (PET) is a potential target for optimization in radiotherapy. However, the implementation of this approach with respect to the conversion of intensities in the images into oxygenation and radiosensitivity maps is not straightforward. This study investigated the feasibility of applying two conversion approaches previously derived for F-labeled fluoromisonidazole (F-FMISO)-PET images for the hypoxia tracer F-flortanidazole (F-HX4).

Consensus statement from the International Radiosurgery Oncology Consortium for Kidney for primary renal cell carcinoma.

Aim: To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma.

Materials & Methods: Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation.

Results: All centers treat patients with pre-existing hypertension and solitary kidneys.

Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation for Solid Cancer.

We wanted to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) may result in long-term survival in patients with solid cancer. HSCT was performed in 61 patients with solid cancer: metastatic renal carcinoma (n = 22), cholangiocarcinoma (n = 17), colon carcinoma (n = 15), prostate cancer (n = 3), pancreatic adenocarcinoma (n = 3), or breast cancer (n = 1). Liver transplantation was performed for tumor debulking in 18 patients.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients.

Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment.

Long-term results of a prospective phase II trial of medically inoperable stage I NSCLC treated with SBRT - the Nordic experience.

Background: Presentation of long term results of a phase II multicenter Nordic trial of medically inoperable stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT).

Material And Methods: We report the extended outcome, focusing on long-term effects, of a prospective cohort of 57 evaluable patients with peripherally located T1N0M0 (72%) and T2N0M0 (28%) NSCLC, treated with SBRT 15 Gy × 3, prescribed to the 67% isodose line encompassing the PTV. The patients were inoperable due to chronic obstructive pulmonary disease (65%), cardiovascular disease (25%) or other illnesses (3%) or refused surgery (7%).

Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies.

The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure.

Treatment fractionation for stereotactic radiotherapy of lung tumours: a modelling study of the influence of chronic and acute hypoxia on tumour control probability.

Background: Stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) has led to promising local control and overall survival for fractionation schemes with increasingly high fractional doses. A point has however been reached where the number of fractions used might be too low to allow efficient local inter-fraction reoxygenation of the hypoxic cells residing in the tumour. It was therefore the purpose of this study to investigate the impact of hypoxia and extreme hypofractionation on the tumour control probability (TCP) from SBRT.

Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma.

Background: To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression- free patient survival.

Methods: Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n=18), sorafenib (n=19) or pazopanib (n=2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression- free survival.

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

Purpose: To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose.

Methods And Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.