Effect of continuous positive airway pressure administration during lung stereotactic ablative radiotherapy: a comparative planning study

Purpose

By increasing lung volume and decreasing respiration-induced tumour motion amplitude, administration of continuous positive airway pressure (CPAP) during stereotactic ablative radiotherapy (SABR) could allow for better sparing of the lungs and heart. In this study, we evaluated the effect of CPAP on lung volume, tumour motion amplitude and baseline shift, as well as the dosimetric impact of the strategy.

Methods

Twenty patients with lung tumours referred for SABR underwent 4D-computed tomography (CT) scans with and without CPAP (CPAP/noCPAP) at two timepoints (T0/T1). First, CPAP and noCPAP scans were compared for lung volume, tumour motion amplitude, and baseline shift. Next, CPAP and noCPAP treatment plans were computed and compared for lung dose parameters (mean lung dose (MLD), lung volume receiving 20 Gy (V_20Gy), 13 Gy (V_13Gy), and 5 Gy (V_5Gy)) and mean heart dose (MHD).

Results

On average, CPAP increased lung volume by 8.0% (p?<?0.001) and 6.3% (p?<?0.001) at T0 and T1, respectively, but did not change tumour motion amplitude or baseline shift. As a result, CPAP administration led to an absolute decrease in MLD, lung V_20Gy, V_13Gy and V_5Gy of 0.1?Gy (p?=?0.1), 0.4% (p?=?0.03), 0.5% (p?=?0.04) and 0.5% (p?=?0.2), respectively, while having no significant influence on MHD.

Conclusions

In patients referred for SABR for lung tumours, CPAP increased lung volume without modifying tumour motion or baseline shift. As a result, CPAP allowed for a slight decrease in radiation dose to the lungs, which is unlikely to be clinically significant.

     

Concurrent radiotherapy with temozolomide vs. concurrent radiotherapy with a cisplatinum-based polychemotherapy regimen

Purpose

As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments.

Methods

Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3–18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials. The HIT-HGG-2007 protocol comprised concomitant radiochemotherapy with temozolomide, while cisplatinum/etoposide (PE) and PE plus ifosfamide (PEI) in combination with weekly vincristine injections were applied during radiochemotherapy in the HIT GBM-C/D protocol.

Results

Regular blood counts and information about cellular nadirs were available from 304 patients (leukocytes) and 306 patients (thrombocytes), respectively. Grade 3–4 leukopenia was much more frequent in the HIT GBM-C/D cohort (n = 88, 52%) vs. HIT-HGG-2007 (n = 13, 10%; P <0.001). Grade 3–4 thrombopenia was also more likely in the HIT GBM-C/D cohort (n = 21, 12% vs. n = 3,2%; P <0.001). Grade 3–4 leukopenia appeared more often in children aged 3–7 years (n = 38/85, 45%) than in children aged 8–12 years (n = 39/120, 33%) and 13–18 years (24/100, 24%; P =0.034). In addition, sickness was more frequent in the HIT GBM-C/D cohort (grade 1–2: 44%, grade 3–4: 6% vs. grade 1–2: 28%, grade 3–4: 1%; P <0.001).

Conclusion

Radiochemotherapy involving cisplatinum-based polychemotherapy is more toxic than radiotherapy in combination with temozolomide. Without evidence of differences in therapeutic efficacy, the treatment with lower toxicity, i.?e., radiotherapy with temozolomide should be used.

     

Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer

Purpose

Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation.

Methods

A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words “stage III non-small cell lung cancer” and “radiotherapy” and “tumour volume” and “prognostic factors”.

Results

After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results.

Conclusion

The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

     

Reirradiation of recurrent node-positive non-small cell lung cancer after previous stereotactic radiotherapy for stage I disease

Background

Practice guidelines have been developed for early-stage and locally advanced non-small cell lung cancer (NSCLC). However, many common clinical scenarios still require individualized decision making. This is true for locoregional relapse after initial stereotactic radiotherapy (stereotactic body radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an increasingly utilized curative treatment option for stage I NSCLC.

Methods

A consortium of expert radiation oncologists was established with the aim of providing treatment recommendations. In this scenario, a case was distributed to six radiation oncologists who provided their institutions’ treatment recommendations. In this case, a patient developed local and mediastinal relapse after SABR (45?Gy, 3 fractions), comparable to the tumor burden in de novo stage IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion was developed.

Results

Three institutions recommended evaluation for surgery. If the patient was not a surgical candidate, and/or refused surgery, definitive chemoradiation was recommended, including retreating the primary to full dose. European participants were more in favor of a non-surgical approach. None of the participants were reluctant to prescribe reirradiation, but two institutions prescribed doses lower than 60?Gy. Platinum-based doublets together with intensity-modulated radiotherapy were preferred.

Conclusion

The institutional recommendations reflect the questions and uncertainties discussed in current stage III guidelines. All institutions agreed that previous SABR is not a contraindication for salvage chemoradiation. In the absence of high-quality prospective trials for recurrent NSCLC, all treatment options recommended in current guidelines for stage III disease can be considered in clinical scenarios such as this.

     

Clinical outcome of stereotactic body radiotherapy of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system

Purpose

The aim of this study was to investigate the clinical outcome of stereotactic body radiotherapy (SBRT) of 54?Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system.

Methods and materials

The subjects were 19 patients who had localized lung tumor (11 primaries, 8 metastases) between May 2003 and October 2005. Treatment was conducted on 19 lung tumors by fixed multiple noncoplanar conformal beams with a standard linear accelerator. The isocentric dose was 54?Gy in nine fractions. The median overall treatment time was 15 days (range 11–22 days). All patients were immobilized by a thermo-shell and a custom-made headrest during the treatment.

Results

The crude local tumor control rate was 95% during the follow-up of 9.4–39.5 (median 17.7) months. In-field recurrence was noted in only one patient at the last follow-up. The Kaplan-Meier overall survival rate at 2 years was 89.5%. Grade 1 radiation pneumonia and grade 1 radiation fibrosis were observed in 12 of the 19 patients. Treatment-related severe early and late complications were not observed in this series.

Conclusion

The stereotactic body radiotherapy of 54?Gy in nine fractions achieved acceptable tumor control without any severe complications. The results suggest that SBRT can be one of the alternatives for patients with localized lung tumors.

     

Timing of radiotherapy following breast-conserving surgery: outcome of 1393 patients at a single institution

Background

The role of postoperative radiotherapy in breast-conserving therapy is undisputed. However, optimal timing of adjuvant radiotherapy is an issue of ongoing debate. This retrospective clinical cohort study was performed to investigate the impact of a delay in surgery–radiotherapy intervals on local control and overall survival.

Patients and methods

Data from an unselected cohort of 1393 patients treated at a single institution over a 17-year period (1990–2006) were analyzed. Patients were assigned to two groups (CT+/CT?) according to chemotherapy status. A delay in the initiation of radiotherapy was defined as >?7 weeks (CT? group) and >?24 weeks (CT+ group).

Results

The 10-year regional recurrence-free survival for the CT? and CT+ groups were 95.6 and 86.0?%, respectively. A significant increase in the median surgery–radiotherapy interval was observed over time (CT? patients: median of 5 weeks in 1990–1992 to a median of 6 weeks in 2005–2006; CT+ patients: median of 5 weeks in 1990–1992 to a median of 21 weeks in 2005–2006). There was no association between a delay in radiotherapy and an increased local recurrence rate (CT? group: p?=?0.990 for intervals 0–6 weeks vs. ≥?7 weeks; CT+ group: p?=?0.644 for intervals 0–15 weeks vs. ≥?24 weeks) or decreased overall survival (CT? group: p?=?0.386 for intervals 0–6 weeks vs. ≥?7 weeks; CT+ group: p?=?0.305 for intervals 0–15 weeks vs. ≥?24 weeks).

Conclusion

In the present cohort, a delay of radiotherapy was not associated with decreased local control or overall survival in the two groups (CT?/CT+). However, in the absence of randomized evidence, delays in the initiation of radiotherapy should be avoided.     

DEGRO practical guidelines: radiotherapy of breast cancer III—radiotherapy of the lymphatic pathways

Aim

The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO).

Methods

A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: “breast cancer”, “radiotherapy”, “regional node irradiation”. Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer.

Results

International guidelines reveal substantial differences regarding indications for RNI. Patients with 1–3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1–2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting.

Conclusion

Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk–benefit relationship appears to shift towards an improvement of outcome.     

Treatment of astrocytoma grade III with Photofrin II as a radiosensitizer

Introduction

Astrocytomas are neoplasms that originate from glial cells. Anaplastic astrocytoma is classified as WHO III, with 27?% of the individuals with grade III astrocytoma living for at least 5 years even after treatment (radiation and chemotherapy). Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models.

Material and methods

This case report presents a woman suffering from an inoperable astrocytoma WHO III since 2004. The patient was treated with radiation therapy and Photofrin II as a radiosensitiser. The patient underwent irradiation with 40?+?20 Gy boost. The patient was given a single intravenous dose of 1 mg/kg Photofrin II 24 h prior to the initiation of radiation therapy.

Results

The patient is still alive without any significant side effect with a follow up of 106 months. MRI shows no evidence of disease.

Conclusion

The follow-up results are encouraging regarding the application of Photofrin II as an effective radiosensitizing agent in the treatment of inoperable WHO III astrocytoma.     

Once-daily radiotherapy to ≥59.4 Gy versus twice-daily radiotherapy to ≥45.0 Gy with concurrent chemotherapy for limited-stage small-cell lung cancer: a comparative analysis of toxicities and outcomes

Purpose  

The aim of this study was to compare toxicities, disease control, survival outcomes, and patterns of failure between groups of limited-stage small-cell lung cancer patients treated with once-daily versus twice-daily radiotherapy and concurrent chemotherapy.     

Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity

Background

In general, late side effects after salvage radiotherapy (RT) for prostate cancer are below 10%. Patients with impaired DNA repair ability and genetic instability can have significantly increased reactions after RT.

Case, clinical follow-up, and examination

We present a patient who experienced severe side effects after additive RT for prostate cancer and died from the complications 25 months after RT. Imaging (MR) is shown as well as three-color fluorescence in situ hybridization. The blood sample testing revealed that radiosensitivity was increased by 35–55%. We undertook a review of the literature to give an overview over the tests established that are currently considered useful.

Conclusion

This case highlights that the identification of patients with increased radiosensitivity is an important task in radiation protection. Groups of patients who should be screened have to be found and corresponding research facilities have to be set up.

     

DEGRO practical guidelines: radiotherapy of breast cancer I

Background and purpose

The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012.

Methods

A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms “breast cancer”, “radiotherapy”, and “breast conserving therapy”. Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer.

Results

Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48–0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75–0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified.

Conclusion

After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit.     

DEGRO practical guidelines: radiotherapy of breast cancer II

Purpose

To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery.

Methods

The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were “non invasive breast cancer”, “ductal carcinoma in situ, “dcis”, “borderline breast lesions”, “lobular neoplasia”, “radiotherapy” and “radiation therapy”. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ.

Results

Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose–volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing.

Conclusion

Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets—even in low risk subgroups (LoE 1a).     

Successful treatment of a rare case of ameloblastic fibrosarcoma with radiation therapy

Sarcomas are rare diseases of the head and neck region, representing around 1% of all malignancies. Amongst them, ameloblastic fibrosarcoma (AFS) is of even greater rarity, with less than 100 cases reported in the literature. Consequently, no standard treatment or guidelines have been made available. Surgery is often performed as primary therapy, but may be limited due to anatomical or functional reasons. We present a case of AFS successfully treated by postoperative radiation therapy. A detailed case study is provided, followed by a review of the English-language literature focusing on the role of radiation therapy.     

Quality control of involved field radiotherapy in the HD 13 and HD 14 trials

Introduction

As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings.

Methods

With the start of the fourth GHSG study generation (HD10–12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13–15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation.

Results

The expert panel analyzed the RT planning and application of 1037 (28?%) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85?% of cases and verification films in 87?%. RT was assessed as major violation in 46?% (HD13 = 38?%, HD14 = 52?%), minor violation in 9?% (HD13 = 9?%, HD14 = 9?%) and according to the protocol in 45?% (HD13 = 52?%, HD14 = 38?%).

Conclusion

The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of “modern RT” in malignant lymphoma.

     

Performance monitoring during postgraduate radiography training in reporting—a case study

Purpose This case study of a radiographer undergoing postgraduate training in radiographic reporting was carried out: to evaluate a monitoring procedure for the development of competence in reporting; and to identify those features of the clinical programme which most improved reporting accuracy.Method Over a 9-week period, 438 reports by a radiographer of the peripheral skeleton were compared with a radiologist's reports of the same films as the reference standard.Results The radiographer's overall sensitivity at the end of the 9-week period was 96.7% and specificity was 98.4%. These values provide no data on how the radiographer's ability changed over time, however, and we show that there was a rising rate of diagnostic accuracy from 87.8% in week 1 to 100% in week 9.Conclusions We attribute the improvement in performance to a number of factors such as familiarization with normal variants, tutorial support on search strategies and increased sophistication in report writing. We use positive and negative predictive values to infer future performance of this radiographer when reporting on patient groups with different injury prevalences. We recommend the practice of monitoring radiographer performance over time in similar training programmes in order to accelerate competence.     

3 T DCE-MRI assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis for treatment response monitoring

Objective

To study the value of 3 T dynamic contrast-enhanced (DCE)-MRI for assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis (EOA) for treatment response monitoring.

Materials and methods

The interphalangeal joints of fingers two to five were examined at 3 T MRI in nine patients with EOA. Two musculoskeletal radiologists recorded erosions, bone marrow oedema (BME), synovitis and osteophytes. Interobserver reliability was calculated using κ statistics. In six patients, DCE-MRI time intensity curves of synovitis in two affected joints were analysed. The maximum upslope, absolute and relative enhancement of synovitis were compared with MRI after 12 months of anti-tumour necrosis factor treatment. Intraobserver reproducibility was calculated using intra-class correlation coefficient.

Results

Interobserver reliability was ‘good’ for detection of erosions (κ?=?0.70), BME (κ?=?0.77) and synovitis (κ?=?0.77), but ‘poor’ for osteophytes (κ?=?0.12). Post-treatment DCE-MRI showed decreasing maximum upslope (p?=?0.002) and absolute (p?=?0.002) and relative (p?=?0.01) enhancement compared to the initial scan. Intraobserver reproducibility of DCE-MRI was ‘almost perfect’ or ‘strong’ for all parameters.

Conclusions

3 T DCE-MRI demonstrates changes in time intensity curves of synovitis in EOA of the interphalangeal joints in a longitudinal study, indicating this technique is promising for monitoring therapy response.