Re-irradiation in locally recurrent lung cancer patients.

PURPOSE: Lung cancer remains one of the tumour diagnoses with high lethality, although innovative treatment approaches have yielded improvements in local control and survival rates. There is still no consensus on how to treat local relapse in patients after first-line treatments. Radiotherapy may be considered in this situation; however, data supporting its effectiveness are rare. The purpose of this retrospective analysis was to evaluate outcomes of patients re-irradiated for thoracic tumours in terms of overall survival (OS), local progression-free survival (LPFS), toxicity and dose-volume parameters. PATIENTS AND METHODS: Sixty-two patients with locally recurrent previously irradiated lung cancer were analysed retrospectively (NSCLC n = 52, SCLC n = 10). Target volumes both in lung and mediastinum were re-irradiated with conventional three-dimensional or intensity-modulated radiotherapy techniques. Median overall dose of re-irradiation was 38.5 Gy (range 20-60 Gy) with a median single dose per fraction of 2 Gy (1.8-3.0 Gy). Clinical documents and treatment plans were evaluated. RESULTS: Median follow-up was 8.2 months (range 0-27 months). OS following re-irradiation was 9.3 months (range: 0-27 months) and LPFS was 6.5 months (range: 0-24 months). OS and LPFS were not affected by histology, total dose or patient age and gender. OS was improved in patients whose re-irradiation volumes included less than two mediastinal lymph node stations (p = 0.016). Twelve patients suffered from pneumonitis ≥grade II (19%) and two from pneumonitis grade III. One patient presumably died from pneumonitis grade V. A slight decline in forced expiratory volume (FEV1) was detected in post-re-irradiation lung function testing. CONCLUSIONS: Re-irradiation is an option for patients with tumour recurrence to control local progression and lower the symptom burden. Oncological outcome appears to be affected by size, location of mediastinal target volumes and lung function. Prospective clinical trials are warranted to substantiate the role of re-irradiation in recurrent lung cancer.

Outcome and prognostic factors in single brain metastases from small-cell lung cancer.

PURPOSE: Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. METHODS: A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. RESULTS: The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). CONCLUSIONS: Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.

Outcome and prognostic factors in patients with brain metastases from small-cell lung cancer treated with whole brain radiotherapy.

The purpose of this study was to evaluate prognostic factors associated with overall survival (OS) and neurological progression free survival (nPFS) in small-cell lung cancer (SCLC) patients with brain metastases who received whole-brain radiotherapy (WBRT). From 2003 to 2015, 229 SCLC patients diagnosed with brain metastases who received WBRT were analyzed retrospectively. In this cohort 219 patients (95%) received a total photon dose of 30 Gy in 10 fractions. The prognostic factors evaluated for OS and nPFS were: age, Karnofsky Performance Status (KPS), number of brain metastases, synchronous versus metachronous disease, initial response to chemotherapy, the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class and thoracic radiation. Median OS after WBRT was 6 months and the median nPFS after WBRT was 11 months. Patients with synchronous cerebral metastases had a significantly better median OS with 8 months compared to patients with metachronous metastases with a median survival of 3 months (p < 0.0001; HR 0.46; 95% CI 0.31-0.67). Based on RPA classification median survival after WBRT was 17 months in RPA class I, 7 months in class II and 3 months in class III (p < 0.0001). Karnofsky performance status scale (KPS < 70%) was significantly associated with OS in both univariate (HR 2.84; p < 0.001) and multivariate analyses (HR 2.56; p = 0.011). Further, metachronous brain metastases (HR 1.8; p < 0.001), initial response to first-line chemotherapy (HR 0.51, p < 0.001) and RPA class III (HR 2.74; p < 0.001) were significantly associated with OS in univariate analysis. In multivariate analysis metachronous disease (HR 1.89; p < 0.001) and initial response to chemotherapy (HR 0.61; p < 0.001) were further identified as significant prognostic factors. NPFS was negatively significantly influenced by poor KPS (HR 2.56; p = 0.011), higher number of brain metastases (HR 1.97; p = 0.02), and higher RPA class (HR 2.26; p = 0.03) in univariate analysis. In this series, the main prognostic factors associated with OS were performance status, time of appearance of intracranial disease (synchronous vs. metachronous), initial response to chemotherapy and higher RPA class. NPFS was negatively influenced by poor KPS, multiplicity of brain metastases, and higher RPA class in univariate analysis. For patients with low performance status, metachronous disease or RPA class III, WBRT should be weighed against supportive therapy with steroids alone or palliative chemotherapy.

Postoperative radiotherapy of patients with thymic epithelial tumors (TET): a retrospective analysis of outcome and toxicity.

PURPOSE: The purpose of this study was to evaluate postoperative radiotherapy regarding outcome and toxicity in patients with thymic epithelial tumors (TET) after surgery. MATERIALS AND METHODS: We retrospectively analyzed medical records of 41 patients with TET treated with postoperative radiotherapy at our institution between 1995 and 2012. The impact of prognostic factors (e.g., Masaoka stage, histological subtype) was investigated and radiation-related toxicity was assessed. RESULTS: Median age was 59.8 years and median follow-up was 61 months. In 24.4 %, TETs were associated with paraneoplastic syndromes. The 5-year overall survival (OS) was 89.5 % and the 5-year disease-free survival (DFS) was 88.9 %. Masaoka stage had a significant impact on OS (p = 0.007). Locally limited stages I + II had a 5-year OS of 100 % compared to 80 % for stage III and 66.7 % for stage IV. The 5-year DFS was excellent with 100 % for both WHO groups A/AB/B1 and B2, respectively, and significantly (p = 0.005) differed from B3/C-staged patients with a 5-year DFS of 63.6 %. Resection status, paraneoplastic association, radiation dose, or tumor size did not influence survival. There were no high-grade acute or late side effects caused by radiotherapy. CONCLUSION: Masaoka stage has a significant impact on OS as WHO type has on DFS in patients with TETs after surgery and adjuvant irradiation. Postoperative radiotherapy with doses around 50 Gy is safe and not likely to cause high-grade toxicity. Further prospective trials are necessary to separate patient subgroups that benefit from radiotherapy from those that do not.

Trimodal therapy for stage III-N2 non-small-cell lung carcinoma: a single center retrospective analysis.

BACKGROUND: Treatment of locally advanced non-small-cell lung cancer is based on a combined approach. To study the impact of trimodal therapy for stage III-N2 NSCLC a single centre retrospective evaluation focusing on survival and therapy-related toxicity was performed. METHODS: 71 patients diagnosed between March 2001 and August 2008 with pathologically confirmed stage III-N2 non-small-cell lung cancer at the University Clinic of Heidelberg were retrospectively analyzed. All patients were treated within trimodal therapy strategies including surgery, induction or adjuvant chemotherapy and postoperative radiotherapy. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. The log-rank test and Fishers Exact test were applied for univariate analysis and Cox proportional regression model for multivariate analysis. RESULTS: Median survival was 32 months. 1-, 3- and 5-year overall survival (OS) rates were 84.5%, 49.6% and 35.5% respectively. Disease free survival rates at 1, 3 and 5 years were 70.4%, 41.8% and 27.4% respectively. 9 patients (12.6%) were diagnosed with a local recurrence. Multivariate analysis did not reveal any independent prognostic factors for OS, but indicated a trend for pT stage and type of surgery. In regard to toxicity 8.4% of the patients developed a clinically relevant ≥ grade 2 pneumonitis. Evaluation of the forced expiratory volume in 1 second per unit of vital capacity (FEV1/VC) before and 1-3 years post radiotherapy revealed a median decrease of 2.1%. CONCLUSIONS: Our descriptive data indicate that trimodal therapy represents an effective and safe treatment approach for patients with stage III-N2 non-small-cell lung cancer. Further prospective clinical trials are necessary in order to clearly define the impact of multimodal strategies and optimize NSCLC treatment.

Chest wall tumor following intravesical BCG instillation for non-muscle invasive bladder cancer.

Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for non-muscle invasive bladder cancer (NMIBC), administered after its transurethral resection. Although its instillation is generally well tolerated, BCG-related infectious complications may occur in up to 5% of patients. Clinical manifestations may arise in conjunction with initial BCG instillation or develop months or years after the last BCG instillation. The range of presentations and potential severity pose an imminent challenge for clinicians. We present a case of an isolated subcutaneous chest wall abscess in an immunocompetent 52-year-old patient nearly two years after intravesical BCG instillation for NMIBC, an absolute rarity. As the enlarging chest wall tumor may be misinterpreted as malignancy, its expedient diagnosis and prompt treatment are of critical importance.

[Update on primary spontaneous pneumothorax - conservative or primarily surgical therapy?] / Update Spontanpneumothorax ­ primär konservativ oder sofortige chirurgische Therapie?

Spontaneous pneumothorax is a potentially life-threatening situation. Therefore, it is mandatory to treat it safely. The incidence is approximately 10 out of 100 000 residents per year. It occurs through an immediate disruption of the visceral pleura that results in an accumulation of air in the pleural space. According to its etiology, spontaneous pneumothorax is divided into 2 groups. Whereas primary spontaneous pneumothorax occurs in healthy individuals without any detectable lung disease, secondary spontaneous pneumothorax occurs in patients with preexisting. Diagnosis of pneumothorax is typically made by chest x-ray. After diagnosis pneumothorax is traditionally treated by an insertion of a thoracic tube.Recently, thoracic ultrasound gained influence in diagnosis of pneumothorax and primarily conservative treatment strategies have been shown to be safe and equally effective in particular groups of patients. This article aims to present and discuss these upcoming strategies.

Genetic Heterogeneity of MET-Aberrant NSCLC and Its Impact on the Outcome of Immunotherapy.

INTRODUCTION: Robust data on the outcome of MET-aberrant NSCLC with nontargeted therapies are limited, especially in consideration of the heterogeneity of MET-amplified tumors (METamp). METHODS: A total of 337 tumor specimens of patients with MET-altered Union for International Cancer Control stage IIIB/IV NSCLC were analyzed using next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry. The evaluation focused on the type of MET aberration, co-occurring mutations, programmed death-ligand 1 expression, and overall survival (OS). RESULTS: METamp tumors (n = 278) had a high frequency of co-occurring mutations (>80% for all amplification levels), whereas 57.6% of the 59 patients with MET gene and exon 14 (METex14) tumors had no additional mutations. In the METamp tumors, with increasing gene copy number (GCN), the frequency of inactivating TP53 mutations increased (GCN < 4: 58.2%; GCN ≥ 10: 76.5%), whereas the frequency of KRAS mutations decreased (GCN < 4: 43.2%; GCN ≥ 10: 11.8%). A total of 10.1% of all the METamp tumors with a GCN ≥ 10 had a significant worse OS (4.0 mo; 95% CI: 1.9-6.0) compared with the tumors with GCN < 10 (12.0 mo; 95% confidence interval [CI]: 9.4-14.6). In the METamp NSCLC, OS with immune checkpoint inhibitor (ICI) therapy was significantly better compared with chemotherapy with 19.0 months (95% CI: 15.8-22.2) versus 8.0 months (95% CI: 5.8-10.2, p < 0.0001). No significant difference in median OS was found between ICI therapy and chemotherapy in the patients with METex14 (p = 0.147). CONCLUSIONS: METex14, METamp GCN ≥ 10, and METamp GCN < 10 represent the subgroups of MET-dysregulated NSCLC with distinct molecular and clinical features. The patients with METex14 do not seem to benefit from immunotherapy in contrast to the patients with METamp, which is of particular relevance for the prognostically poor METamp GCN ≥ 10 subgroup.

Correlation of patient-related factors and dose-volume histogram parameters with the onset of radiation pneumonitis in patients with small cell lung cancer.

PURPOSE: To analyze the association of patient- and treatment-related factors with the onset of radiation pneumonitis in a homogeneously treated cohort of patients suffering from small cell lung cancer (SCLC). PATIENTS AND METHODS: 242 patients with SCLC staged as limited disease, who had been treated with chemotherapy and three-dimensional conformal radiotherapy, were retrospectively analyzed. Pneumonitis was defined by typical symptoms and radiographic findings and judged clinically relevant, if drug administration and hospitalization were necessary. Patient- (age, gender, smoking history, performance status, tumor localization, benign lung disease) and treatment-related parameters (V(10)-V(40), mean lung dose [MLD]) were analyzed using χ(2)-tests for categorical parameters and logistic regression for continuous variables. RESULTS: 33 patients (13.6%) developed a clinically relevant pneumonitis, of whom three patients died. All cases of pneumonitis developed within 120 days. None of the patient-related parameters correlated significantly with the onset of pneumonitis. Considering treatment-related parameters, a significant correlation of V(30) in regard to total lung and V(40) in regard to ipsilateral, contralateral and total lung to the risk of pneumonitis was found. So, the estimated risk of a clinically relevant pneumonitis increased from 10% given a V(30) of 13% to 30% given a V(30) of 35%. In contrast, no significant correlation was found for V(10) and V(20) and only a trend for MLD. CONCLUSION: In this series, high-dose radiation volume parameters, i.e., V(30) and especially V(40), were identified as the most important factors for the development of radiation pneumonitis. Low-dose radiation volume parameters and clinical parameters played an inferior role in predicting the pneumonitis risk.

Impact of inflammatory markers on survival in patients with limited disease small-cell lung cancer undergoing chemoradiotherapy.

BACKGROUND: Systemic inflammation appears to play a role in the progression of numerous solid tumors by promoting tumor proliferation. Our current study aimed to evaluate the role of inflammatory markers in limited disease (LD) small-cell lung cancer (SCLC) patients undergoing thoracic chemoradiotherapy (TCR). PATIENTS AND METHODS: We retrospectively analyzed a total number of 350 SCLC patients diagnosed with LD SCLC who received TCR between 1999 and 2017 and had available blood tests within 2 weeks prior to the start of TCR. Serum C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), hemoglobin (Hb) levels, and platelet count (Pc) were evaluated as potential inflammatory markers. Kaplan-Meier survival analysis was performed for overall survival (OS). For comparison of survival curves, the log-rank (Mantel-Cox) test was used. Univariate and multivariate Cox proportional HRs were used to assess the influence of cofactors on OS. RESULTS: Univariate analysis for OS revealed a statistically significant effect for LDH >400 U/L (HR 2.05 U/L; 95% CI 1.29-3.26 U/L; P=0.002), prophylactic cranial irradiation (PCI; HR 0.58; 95% CI 0.40-0.85; P=0.005), CRP >50 mg/L (HR 1.49 mg/L; 95% CI 1.05-2.10 mg/L; P=0.026), and Karnofsky performance scale (KPS) <70% (HR 1.35%; 95% CI 1.02-1.80%; P=0.035). NLR, age (>70 years), Hb levels, and Pc did not influence survival. In multivariate analysis, OS was significantly affected by PCI (HR 0.64; 95% CI 0.43-0.94; P=0.026), LDH >400 U/L (HR 1.91 U/L; 95% CI 1.21-3.05 U/L; P=0.006), and CRP >50 mg/L (HR 1.43 mg/L; 95% CI 1.01-2.04 mg/L; P=0.045). KPS (≤70%) did not influence survival in multivariate analysis. CONCLUSION: Elevated CRP and LDH seem to be the independent prognostic factors for OS in LD SCLC patients undergoing TCR. However, elevated NLR was not found to be an independent prognostic factor for OS if taken prior to TCR. LDH and CRP are easily available blood tests and do not require additional resources for routine use and could be useful for clinical decision making.

Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices.

INTRODUCTION: Patients with small-cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT. PATIENTS AND METHODS: The present study was conducted utilizing a single-institution, previously described, retrospective database of patients with SCLC who were treated with WBRT (n = 221). Univariate and multivariate analyses were performed to generate the "brain metastases from SCLC score" (BMS score) based on favorable prognostic factors: Karnofsky performance status (KPS > 70), extracerebral disease status (stable disease/controlled), and time of appearance of BM (synchronous). Furthermore, the disease-specific graded prognostic assessment score as well as the recursive partitioning analysis (RPA) were performed and compared with the new BMS score by using the log-rank (Mantel-Cox) test. RESULTS: BMS score and RPA showed the most significant differences between classes (P < .001). BMS score revealed a mean overall survival (OS) of 2.62 months in group I (0-1 points), 6.61 months in group II (2-3 points), and 12.31 months in group III (4 points). The BMS score also identified the group with the shortest survival (2.62 months in group I), and the numbers of patients in each group were most equally distributed with the BMS score. CONCLUSION: The new BMS score was more prognostic than the RPA and disease-specific graded prognostic assessment scores. The BMS score is easy to use and reflects known prognostic factors in contemporary patients with SCLC treated with WBRT. Future studies are necessary to validate these findings.

Whole brain radiation therapy alone versus radiosurgery for patients with 1-10 brain metastases from small cell lung cancer (ENCEPHALON Trial): study protocol for a randomized controlled trial.

BACKGROUND: Conventional whole brain radiotherapy (WBRT) has been established as the treatment standard in patients with cerebral metastases from small-cell lung cancer (SCLC), however, it has only modest efficacy and limited prospective data is available for WBRT as well as local treatments such as stereotactic radiosurgery (SRS). METHODS/DESIGN: The present single-center prospective randomized study, conducted at Heidelberg University Hospital, compares neurocognitive function, as objectively measured by significant deterioration in Hopkins Verbal Learning Test - Revised total recall at 3 months. Fifty-six patients will be randomized to receive either SRS of all brain metastases (up to ten lesions) or WBRT. Secondary endpoints include intracranial progression (local tumor progression and number of new cerebral metastases), extracranial progression, overall survival, death due to brain metastases, local (neurological) progression-free survival, progression-free survival, changes in other cognitive performance measures, quality of life and toxicity. DISCUSSION: Recent evidence suggests that SRS might be a promising treatment option for SCLC patients with brain metastases. The present trial is the first to prospectively investigate the treatment response, toxicity and neurocognition of WBRT and SRS in SCLC patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT03297788 . Registered September 29, 2017.

Parenchymal and Functional Lung Changes after Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer-Experiences from a Single Institution.

INTRODUCTION: This study aimed to evaluate parenchymal and functional lung changes following stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) patients and to correlate radiological and functional findings with patient and treatment characteristics as well as survival. MATERIALS AND METHODS: Seventy patients with early-stage NSCLC treated with SBRT from 2004 to 2015 with more than 1 year of CT follow-up scans were analyzed. Incidence, morphology, severity of acute and late lung abnormalities as well as pulmonary function changes were evaluated and correlated with outcome. RESULTS: Median follow-up time was 32.2 months with 2-year overall survival (OS) of 83% and local progression-free survival of 88%, respectively. Regarding parenchymal changes, most patients only developed mild to moderate CT abnormalities. Mean ipsilateral lung dose (MLD) in biological effective dose and planning target volume size were significantly associated with maximum severity score of parenchymal changes (p = 0.014, p < 0.001). Furthermore, both maximum severity score and MLD were significantly connected with OS in univariate analysis (p = 0.043, p = 0.025). For functional lung changes, we detected significantly reduced total lung capacity, forced expiratory volume in 1 s, and forced vital capacity (FVC) parameters after SBRT (p ≤ 0.001). Multivariate analyses revealed SBRT with an MLD ≥ 9.72 Gy and FVC reduction ≥0.54 L as independent prognostic factors for inferior OS (p = 0.029, p = 0.004). CONCLUSION: SBRT was generally tolerated well with only mild toxicity. For evaluating the possible prognostic impact of MLD and FVC reduction on survival detected in this analysis, larger prospective studies are truly needed.

Histology of non-small cell lung cancer predicts the response to stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To investigate the prognostic impact of different histological subtypes of non-small cell lung cancer (NSCLC) on outcome following stereotactic body radiotherapy (SBRT) for NSCLC patients. MATERIALS AND METHODS: We analyzed 126 consecutive patients with early-stage adenocarcinoma or squamous cell carcinoma treated with SBRT from 2004 to 2016. Adenocarcinoma patients were further sub-classified as high-risk or low-risk tumors. RESULTS: With a median follow-up time of 22months, 2-year overall survival (OS), local (LC), and distant control (DC) were 68%, 90% and 79%, respectively. For LC, histologic subtype was identified as major independent prognostic factor (p=0.033): while LC was 81% for squamous cell carcinoma patients, LC was significantly improved for high-risk and even more non-high-risk adenocarcinoma patients with 96% and 100%, respectively (p=0.026). The negative prognostic impact of the histologic subtype "squamous cell carcinoma" was not evident when patients received SBRT with higher total doses in EQD2 (2Gy equivalent dose): if patients were treated with a total dose in EQD2≥150Gy, no significant difference in LC for histologic subtypes was detected anymore (p=0.355). CONCLUSION: In the current study, histologic subtypes of NSCLC predicted local control probabilities following SBRT. Prospective, multi-center studies are needed to evaluate the prognostic impact of histology and consecutively the need for SBRT dose adaptation.

Nine-year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-cell Lung Cancer.

BACKGROUND: In 2007, the European Organization for Research and Treatment of Cancer (EORTC) study (ClinicalTrials.gov identifier, NCT00016211) demonstrated a beneficial effect on overall survival (OS) with the use of prophylactic cranial irradiation (PCI) for extensive disease (ED) small-cell lung cancer (SCLC). Nevertheless, debate is ongoing regarding the role of PCI, because the patients in that trial did not undergo magnetic resonance imaging (MRI) of the brain before treatment. Also, a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain MRI findings. MATERIALS AND METHODS: We examined the medical records of 136 patients with ED SCLC who had initially responded to chemotherapy and undergone PCI from 2007 to 2015. The outcomes, radiation toxicity, neurologic progression-free survival, and OS after PCI were analyzed. Survival and correlations were calculated using log-rank and univariate Cox proportional hazard ratio analyses. RESULTS: The median OS and the median neurologic progression-free survival after PCI was 12 and 19 months, respectively. No significant survival difference was seen for patients who had undergone MRI before PCI compared with patients who had undergone contrast-enhanced computed tomography (P = .20). Univariate analysis for OS did not show a statistically significant effect for known cofactors. CONCLUSION: In the present cohort, PCI was associated with improved survival compared with the PCI arm of the EORTC trial, with a nearly doubled median OS period. Also, the median OS was prolonged by 2 months compared with the irradiation arm of the Japanese trial.

Establishing stereotactic body radiotherapy with flattening filter free techniques in the treatment of pulmonary lesions - initial experiences from a single institution.

BACKGROUND: Stereotactic body radiotherapy (SBRT) using flattening filter free (FFF)-techniques has been increasingly applied during the last years. However, clinical studies investigating this emerging technique are still rare. Hence, we analyzed toxicity and clinical outcome of pulmonary SBRT with FFF-techniques and performed dosimetric comparison to conventional techniques using flattening filters (FF). MATERIALS AND METHODS: Between 05/2014 and 06/2015, 56 consecutive patients with 61 pulmonary lesions were treated with SBRT in FFF-mode. Central lesions received 8 × 7.5 Gy delivered to the conformally enclosing 80 %-isodose, while peripheral lesions were treated with 3 × 15 Gy, prescribed to the 65 %-isodose. Early and late toxicity (after 6 months) as well as initial clinical outcomes were evaluated. Furthermore, [deleted] plan quality and efficiency were evaluated by analyzing conformity, beam- on and total treatment delivery times in comparison to plans with FF-dose application. RESULTS: Median follow-up time was 9.3 months (range 1.5-18.0 months). Early toxicity was low with only 5 patients (8.9 %) reporting CTCAE 2° or higher side-effects. Only one patient (1.8 %) was diagnosed with radiation-induced pneumonitis CTCAE 3°, while 2 (3.6 %) patients suffered from pneumonitis CTCAE 2°. After 6 months, no toxicity greater than CTCAE 2° was reported. 1-year local progression-free survival, distant progression-free survival and overall survival were 92.8 %, 78.0 %, and 94.4 %, respectively. While plan quality was similar for FFF- and FF-plans in respect to conformity (p = 0.275), median beam-on time as well as total treatment time were significantly reduced for SBRT in FFF-mode compared to FF-mode (p ≤ 0.001, p ≤ 0.001). CONCLUSIONS: Patient treatment with SBRT using FFF-techniques is safe and provides promising clinical results with only modest toxicity at significantly increased dose delivery speed.

Outcome in patients with small cell lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation.

OBJECTIVES: Patients with brain metastases from small-cell lung cancer (SCLC) who underwent prior prophylactic cranial irradiation (PCI) are often treated with a second course of whole brain radiation therapy (Re-WBRT) or stereotactic radiosurgery (SRS) for purposes of palliation in symptomatic patients, hope for increased life expectancy or even as an alternative to untolerated steroids. Up to date there is only limited data available regarding the effect of this treatment. This study examines outcomes in patients in a single institution who underwent cerebral re-irradiation after prior PCI. METHODS: We examined the medical records of 76 patients with brain metastases who had initially received PCI between 2008 and 2015 and were subsequently irradiated with a second course of cerebral radiotherapy. Patients underwent re-irradiation using either Re-WBRT (88%) or SRS (17%). The outcomes, including symptom palliation, radiation toxicity, and overall survival (OS) following re-irradiation were analyzed. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses. Treatment-related toxicity was classified according to CTCAE v4.0. RESULTS: Median OS of all patients was 3 months (range 0-12 months). Median OS after Re-WBRT was 3 months (range 0-12 months). Median OS after SRS was 5 months (range 0-12 months). Karnofsky performance status scale (KPS ≥50%) was significantly associated with improved OS in both univariate (HR 2772; p=0,009) and multivariate analyses (HR 2613; p=0,024) for patients receiving Re-WBRT. No unexpected toxicity was observed and the observed toxicity remained consistently low. Symptom palliation was achieved in 40% of symptomatic patients. CONCLUSIONS: In conclusion, cerebral re-irradiation after prior PCI is beneficial for symptom palliation and is associated with minimal side effects in patients with SCLC. Our survival data suggests that it is primarily useful in patients with adequate performance status.

Outcome and prognostic factors of postoperative radiation therapy (PORT) after incomplete resection of non-small cell lung cancer (NSCLC).

PURPOSE: Current guidelines recommend postoperative radiation therapy (PORT) for incompletely resected non-small cell lung cancer (NSCLC). However, there is still a paucity of evidence for this approach. Hence, we analyzed survival in 78 patients following radiotherapy for incompletely resected NSCLC (R1) and investigated prognostic factors. PATIENTS AND METHODS: All 78 patients with incompletely resected NSCLC (R1) received PORT between December 2001 and September 2014. The median total dose for PORT was 60 Gy (range 44-68 Gy). The majority of patients had locally advanced tumor stages (stage IIA (2.6%), stage IIB (19.2%), stage IIIA (57.7%) and stage IIIB (20.5%)). 21 patients (25%) received postoperative chemotherapy. RESULTS: Median follow-up after radiotherapy was 17.7 months. Three-year overall (OS), progression-free (PFS), local (LPFS) and distant progression-free survival (DPFS) rates were 34.1, 29.1, 44.9 and 51.9%, respectively. OS was significantly prolonged at lower nodal status (pN0/1) and following dose-escalated PORT with total radiation doses >54 Gy (p=0.012, p=0.013). Furthermore, radiation doses >54 Gy significantly improved PFS, LPFS and DPFS (p=0.005; p=0.050, p=0.022). Interestingly, survival was neither significantly influenced by R1 localization nor by extent (localized vs. diffuse). Multivariate analyses revealed lower nodal status and radiation doses >54.0 Gy as the only independent prognostic factors for OS (p=0.021, p=0.036). CONCLUSION: For incompletely resected NSCLC, PORT is used for improving local tumor control. Local progression is still the major pattern of failure. Radiation doses >54 Gy seem to support improved local control and were associated with better OS in this retrospective study.

The dynamic pattern of recurrence in curatively resected non-small cell lung cancer patients: Experiences at a single institution.

PURPOSE: To investigate the hazard function of tumor recurrence in patients with completely (R0) resected non-small cell lung cancer. METHODS: A total of 1374 patients treated between 2003 and 2009 with complete resection and systematic lymph node dissection were studied. The risk of recurrence at a given time after operation was studied utilizing the cause-specific hazard function. Recurrence was categorized as local recurrence or distant recurrence. The risk distribution was assessed using clinical and pathological factors. RESULTS: The hazard function for recurrence presented an early peak at approximately 10 months after surgery and maintained a tapered plateau-like tail extending up to 8 years. A similar risk pattern was detected for both local recurrence and distant recurrence, while the risk of distant recurrence was higher than that of local recurrence. The double-peaked pattern of hazard rate was present in several subgroups, such as p-stage IA patients. A comparison of histology and status of nodal involvement showed that pN1-2 adenocarcinoma patients demonstrated a high hazard rate of distant recurrence and that pN0 adenocarcinoma patients exhibited a small recurrent risk for a longer time. Squamous cell carcinoma patients showed only little difference in risk. CONCLUSIONS: The data may be useful to select patients at high risk of recurrence and may provide information for each patient to decide how to manage the postoperative follow-up individually.

Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas.

BACKGROUND: There is controversy whether patients diagnosed with large-cell neuroendocrine carcinoma (LCNEC) should be treated according to protocols for non-small cell lung cancers (NSCLC) or small cell lung cancers (SCLC), especially with regard to the administration of prophylactic cranial irradiation (PCI). This study was set up to determine the incidence of brain metastases and to investigate the outcome following multimodal treatment in 70 patients with LCNEC. METHODS: Seventy patients with histologically confirmed LCNEC were treated at the University Hospital of Heidelberg between 2001 and 2014. Data were collected retrospectively. Al most all patients received thoracic surgery as initial treatment (94 %). Chemotherapy was administered in 32 patients as part of the initial treatment. Fourteen patients were treated with adjuvant or definitive thoracic radiotherapy according to NSCLC protocols. Cranial radiotherapy due to brain metastases, mostly given as whole brain radiotherapy (WBRT), was received by fourteen patients. Statistical analysis was performed using the long-rank test and the Kaplan-Meier method. RESULTS: Without PCI, the detected rate for brain metastases was 25 % after a median follow-up time of 23.4 months, which is comparable to NSCLC patients in general. Overall (OS), local (LPFS), brain metastases-free survival (BMFS) and extracranial distant progression-free survival (eDPFS) was 43, 50, 63 and 50 % at 5 years, respectively. Patients with incomplete resection showed a survival benefit from adjuvant radiotherapy. The administration of adjuvant chemotherapy improved the general worse prognosis in higher pathologic stages. CONCLUSION: In LCNEC patients, the administration of radiotherapy according to NSCLC guidelines appears reasonable and contributes to acceptable results of multimodal treatment regimes. The low incidence of spontaneous brain metastases questions a possible role of PCI.