PET/CT imaging for evaluation of multimodal treatment efficacy and toxicity in advanced NSCLC-current state and future directions.

PURPOSE: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, leading to a string of approvals in recent years. Herein, a narrative review on the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the ever-evolving treatment landscape of advanced NSCLC is presented. METHODS: This comprehensive review will begin with an introduction into current treatment paradigms incorporating ICIs; the evolution of CT-based criteria; moving onto novel phenomena observed with ICIs and the current state of hybrid imaging for diagnosis, treatment planning, evaluation of treatment efficacy and toxicity in advanced NSCLC, also taking into consideration its limitations and future directions. CONCLUSIONS: The advent of ICIs marks the dawn of a new era bringing forth new challenges particularly vis-à-vis treatment response assessment and observation of novel phenomena accompanied by novel systemic side effects. While FDG PET/CT is widely adopted for tumor volume delineation in locally advanced disease, response assessment to immunotherapy based on current criteria is of high clinical value but has its inherent limitations. In recent years, modifications of established (PET)/CT criteria have been proposed to provide more refined approaches towards response evaluation. Not only a comprehensive inclusion of PET-based response criteria in prospective randomized controlled trials, but also a general harmonization within the variety of PET-based response criteria is pertinent to strengthen clinical implementation and widespread use of hybrid imaging for response assessment in NSCLC.

External Validation of a Survival Score for Limited-Stage Small Cell Lung Cancer Patients Treated with Chemoradiotherapy.

PURPOSE: In order to personalize multimodal treatment regimens in limited-stage small cell lung cancer (LS-SCLC), a survival score for these patients was proposed. The aim of this study is to validate the score in an independent external patient cohort. METHODS: We collected data of 78 patients treated with chemoradiotherapy for LS-SCLC between 2004 and 2015. The survival score was calculated by independent prognostic factors: gender, Karnofsky performance status, tumor substage, and hemoglobin level before treatment. Scoring points were derived from 2-year survival rates divided by 10 and the values for each prognostic factor were tallied. Three risk subgroups were defined (high, intermediate, low risk: 9-13, 14-18, 19-26 points). The 2-year survival rate of each subgroup from the original study was compared to its corresponding subgroup from the validation cohort. RESULTS: Median survival time in the entire validation cohort was 17 months (range: 1-123 months). The 2-year survival rates were 0% in the 9-13, 35% in the 14-18, and 43% in the 19-26 points group, respectively (p = 0.018). The difference in 2-year survival between the 9-13 points and the 14-18 points group was significant in the validation cohort (p = 0.007) as well after stratification of concurrent chemoradiotherapy (p < 0.001), whereas the difference between the 14 and 18 points and the 19-26 points group was not significant (p = 0.602, p = 0.770). CONCLUSION: The score was reproducible to estimate the 2-year survival rate of patients with LS-SCLC, especially in the high- and intermediate-risk subgroups. In order to improve the differentiation between patients with an intermediate and favorable survival prognosis, the scoring system needs further development.

Medulloblastoma in adults : A retrospective single institution analysis.

PURPOSE: Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution. METHODS: Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients' demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated. RESULTS: In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2 Gy) and a boost to the posterior fossa (median dose 19.8 Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5­ and 10-year OS was 89 and 80%, respectively. Estimated 5­ and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS. CONCLUSIONS: The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible.

Correction to: Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer.

Correction to: Strahlenther Onkol 2017 https://doi.org/10.1007/s00066-017-1229-3 Unfortunately, an incorrect reference was provided in Table 4.The corrected version of Table 4 can be found below.We apologize for any inconvenience ….

Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer.

PURPOSE: Positron emission tomography with 2­deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG-PET/CT) has an established role in the initial diagnosis and staging of lung cancer. However, a prognostic value of PET/CT during multimodality treatment has not yet been fully clarified. This study evaluated the role of primary tumor metabolic volume (PT-MV) changes on PET/CT before, during, and after chemoradiotherapy (CRT). METHODS: A total of 65 patients with non-small-cell lung cancer (NSCLC) UICC stage IIIA/B (TNM 7th Edition) were treated with definitive chemoradiotherapy (sequential or concurrent setting). PET/CT was acquired before the start, at the end of the third week, and 6 weeks following CRT. RESULTS: Median overall survival (OS) for the entire cohort was 16 months (95% confidence interval [CI]: 12-20). In all, 60 (92.3%) patients were eligible for pre-treatment (pre-PT-MV), 28 (43%) for mid-treatment (mid-PT-MV), and 53 (81.5%) for post-treatment (post-PT-MV) volume analysis. Patients with pre-PT-MV >63 cm3 had worse OS (p < 0.0001). A reduction from mid-PT-MV to post-PT-MV of >15% improved OS (p = 0.001). In addition, patients with post-PT-MV > 25 cm3 had significantly worse outcome (p = 0.001). On multivariate analysis, performance status (p = 0.002, hazard ratio [HR] 0.007; 95% CI 0.00-0.158), pre-PT-MV1 < 63 cm3 (p = 0.027, HR 3.98; 95% CI 1.17-13.49), post-PT-MV < 25 cm3 (p = 0.013, HR 11.90; 95% CI 1.70-83.27), and a reduction from mid-PT-MV to post-PT-MV > 15% (p = 0.004, HR 0.25; 95% CI 0.02-0.31) correlated with improved OS. CONCLUSIONS: Our results demonstrated that pre- and post-treatment PT-MV, as well as an at least 15% reduction in mid- to post-PT-MV, significantly correlates with OS in patients with inoperable locally advanced NSCLC.

How much primary tumor metabolic volume reduction is required to improve outcome in stage III NSCLC after chemoradiotherapy? A single-centre experience.

PURPOSE: We analysed a correlation between pre- to post-treatment primary tumour metabolic volume (PT-MV) reduction on 18F-FDG-PET/CT and survival in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). METHODS: Sixty consecutive patients with NSCLC stage IIIA-B (UICC 7th edition), treated with chemoradiotherapy, who underwent 18F-FDG-PET/CT at the same institution before and 6 weeks after treatment, were analysed. Different metabolic response values were investigated on their correlation with survival parameters: complete response (100% PT-MV reduction); major response (80-99% PT-MV reduction); moderate response (50-79% PT-MV reduction); minor response (1-49% PT-MV reduction) and non-response (no change or increase in uptake). RESULTS: From 60 patients, 52 (87%) had repeat PET/CT scans 6 weeks after completion of CRT. Complete metabolic response (CR) was reached in ten (17%), whereas major and moderate metabolic responses occurred in 16 (27%) and 15 (25%) patients, respectively. Four patients (7%) had minor metabolic response. Non-response was documented in seven patients (12%). Median overall survival (MS) for the entire cohort was 17 months (95% CI: 11.9-22.1 months). MS according to the different metabolic response values was as follows: 34 months (95% CI: 0-84.1); 22 months (95% CI: 14.2-29.8); 12 months (95% CI: 0.4-23.6); 11 months (95% CI: 0.2-21.8) and 17 months in patients with complete, major, moderate, minor and non-response (95% CI: 6.7-27.3), respectively (p = 0.008). On multivariate analysis, significant predictors of survival included ECOG performance status (p = 0.035, HR 0.49, 95% CI: 0.25-0.95) as well as complete and major metabolic response as a continuous variable with PT-MV reduction of at least 80% (p = 0.021, HR 0.36, 95% CI: 0.15-0.86). Moderate metabolic response did not correlate with improved outcome (p = 0.522). CONCLUSIONS: In this homogeneous locally-advanced NSCLC single-centre patient cohort, a PT-MV reduction of at least 80% (complete and major metabolic response) following CRT was necessary to significantly improve patient outcome.

Prognostic role of patient gender in limited-disease small-cell lung cancer treated with chemoradiotherapy.

BACKGROUND: Previous studies have demonstrated that female gender could be a prognostic factor in limited-disease (LD) small-cell lung cancer (SCLC), but the correlation between patient gender and survival parameters remains unclear. PATIENTS AND METHODS: Data from 179 LD SCLC patients treated with definitive chemoradiotherapy (CRT) were reviewed. Influence of patient gender on time to progression (TTP), local control (LC), brain metastasis-free (BMFS), distant metastasis-free (DMFS) and overall survival (OS) was analysed. RESULTS: Definitive CRT was completed by 179 (110 men/69 women) patients. Of these, 68 (38%; 34 men/34 women) patients were treated in concurrent and 111 (62%; 76 men/35 women) in sequential mode. Prophylactic cranial irradiation (PCI) was subsequently applied in 70 (39%; 36 men/34 women) patients with partial or complete response after CRT. Median OS was 20 (95% confidence interval [CI] 10-22) and 14 (95% CI 10-18) months in female and male patients, respectively (p = 0.021). In subgroups defined by remission status (complete and partial response) after CRT, an OS benefit for females compared to males was also detected. There was no correlation between patient gender and TTP, LC or DMFS, and no difference in OS in the female and male subgroups treated with PCI. The incidence of metachronous brain metastases (BMs) in the male and female subgroups differed significantly (40/110 men vs. 18/69 women, p = 0.03). Also, mean BMFS was significantly longer in women (p = 0.023). Patient gender also significantly correlated with OS on multivariate analysis after adjustment for other prognostic factors (p = 0.04, HR 1.38, 95% CI 1.08-1.92). CONCLUSION: In this heterogeneous LD SCLC patient cohort treated with definitive CRT, female gender was significantly associated with longer BMFS and OS, as well as with a lower incidence of metachronous brain failure.

Evaluation of the role of remission status in a heterogeneous limited disease small-cell lung cancer patient cohort treated with definitive chemoradiotherapy.

BACKGROUND: The role of remission status in limited disease (LD) small-cell lung cancer (SCLC) patients treated with definitive chemoradiotherapy (CRT) remains to be finally clarified. METHODS: Individual data from 184 patients treated with definitive CRT concurrently or sequentially were retrospectively reviewed. Kaplan-Meier analysis as well as univariate and multivariate Cox regression models were used to describe survival within patient subgroups defined by remission status. RESULTS: 71 (39%) patients were treated in the concurrent, 113 (61%) in the sequential CRT mode. Prophylactic cranial irradiation (PCI) was applied in 71 (39%) patients. 37 (20%) patients developed local, while 89 (48%) distant recurrence. 58 (32%) patients developed metachronous brain metastases. Complete, partial remission and non-response (defined as stable and progressive disease) were documented in 65 (35%), 77 (42%), and 37 (20%) patients, respectively. In complete responders median overall survival was 21.8 months (95CI: 18.6 - 25) versus 14.9 (95% CI: 11.7 - 18.2) (p = 0.041, log-rank test) and 11.5 months (95% CI: 8.9 - 15.0) (p < 0.001, log-rank test) in partial and non-responders, respectively. The same effect was documented for the time to progression and distant metastasis-free survival. In the multivariate analysis achievement of complete remission as a variable shows a trend for the prolonged time to progression (p = 0.1, HR 1.48) and distant metastasis-free survival (p = 0.06, HR 1.63) compared to partial responders and was highly significant compared to non-responders. CONCLUSION: In this treated heterogeneous LD SCLC patient cohort complete remission was associated with longer time to progression, distant metastasis-free and overall survival compared to the non- and especially partial responders.

Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas.

PURPOSE: Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown. METHODS: Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models. RESULTS: Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence. CONCLUSION: The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.

Implementation of durvalumab maintenance treatment after concurrent chemoradiotherapy in inoperable stage III non-small cell lung cancer (NSCLC)-a German radiation oncology survey.

BACKGROUND: Durvalumab as maintenance treatment after platinum-based concurrent chemoradiotherapy (cCRT) has become the standard of care in inoperable stage III non-small cell lung cancer (NSCLC). In this nationwide survey, we solicited members of the German Radiation Oncology Society to review the current distribution and clinical settings of durvalumab treatment after cCRT, observed side effects and summarize follow-up management. METHODS: We surveyed radiation oncology institutions in Germany via an anonymous online questionnaire sent by e-mail to all members of the German Radiation Oncology Society which agreed their willingness to participate. RESULTS: We received a total of 255 responses (response rate: 18%). Of which 203 (80%) were completed and returned and thus eligible for further evaluation. The respondents work in 87 different cities and 44% in a private medical practice, 29% in university and 22% in a general hospital. Durvalumab was implemented in clinical routine by 70% of respondents. Major reasons for failed implementation in clinical practice reported by the respondents were patient's ineligibility (42%), lack of required PD-L1 status (25%), decision of medical oncologists (7%) or absence of updated German guidelines (7%). Thirty-six percent of all respondents report low (≤30%) PD-L1 testing before cCRT based on IHC assay. No respondent had applied durvalumab in less than 14 days after the completion of CRT. Severe side effects requiring hospital admission in more than 10% of all patients were reported by 12% of all respondents. CONCLUSIONS: Durvalumab maintenance is already implemented in the radiation oncology community and administered by the absolute majority of respondents. Low testing rates of PD-L1 at initial diagnosis were observed and should be considered a major barrier to universal adoption and integration in the clinical work-flow in countries with durvalumab approval restricted to PD-L1 positive patients. No respondent applies durvalumab in less than 14 days after cCRT.

Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: immunological rationale and current clinical trials establishing a novel multimodal strategy.

Immune-checkpoint inhibitors (ICI) have dramatically changed the landscape of lung cancer treatment. Preclinical studies investigating combination of ICI with radiation show a synergistic improvement of tumor control probability and have resulted in the development of novel therapeutic strategies. For advanced non-small cell lung cancer (NSCLC), targeting immune checkpoint pathways has proven to be less toxic with more durable treatment response than conventional chemotherapy. In inoperable Stage III NSCLC, consolidation immune checkpoint inhibition with the PD-L1 inhibitor durvalumab after completion of concurrent platinum-based chemoradiotherapy resulted in remarkable improvement of progression-free and overall survival. This new tri-modal therapy has become a new treatment standard. Development of predictive biomarkers and improvement of patient selection and monitoring is the next step in order to identify patients most likely to derive maximal benefit from this new multimodal approach. In this review, we discuss the immunological rationale and current trials investigating chemoradioimmunotherapy for inoperable stage III NSCLC.

Association of Planning Target Volume with Patient Outcome in Inoperable Stage III NSCLC Treated with Chemoradiotherapy: A Comprehensive Single-Center Analysis.

Inoperable stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous patient cohort. Multimodal treatment approaches including radiotherapy have been the new standard of care, with promising outcomes. The planning target volume (PTV), including the primary tumor, involved lymph node stations and safety margins, can vary widely. In order to evaluate the impact of the PTV for overall survival (OS), progression-free survival (PFS) and loco-regional control, we analyzed retrospective and prospective data of 122 consecutive patients with inoperable stage III NSCLC treated with CRT. The majority of patients (93%) received a total dose ≥ 60 Gy and 92% of all patients were treated with concurrent or sequential chemotherapy. Median follow-up for the entire cohort was 41.2 (range: 3.7-108.4) months; median overall survival (OS) reached 20.9 (95% CI: 14.5-27.3) months. PTVs from 500 to 800 ccm were evaluated for their association with survival in a univariate analysis. In a multivariate analysis including age, gender, total radiation dose and histology, PTV ≥ 700 ccm remained a significant prognosticator of OS (HR: 1.705, 95% CI: 1.071-2.714, p = 0.025). After propensity score matching (PSM) analysis with exact matching for Union internationale contre le cancer (UICC) TNM Classification (7th ed.)T- and N-stage, patients with PTV < 700 ccm reached a median PFS and OS of 11.6 (95% CI: 7.3-15.9) and 34.5 (95% CI: 25.6-43.4) months vs. 6.2 (95% CI: 3.1-9.3) (p = 0.057) and 12.7 (95% CI: 8.5-16.9) (p < 0.001) months in patients with PTV ≥ 700 ccm, respectively. Inoperable stage III NSCLC patients with PTV ≥ 700 ccm had significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC.

Blood Parameters Demonstrating a Significant Survival Impact in Patients With Locally Advanced NSCLC Undergoing Definitive Chemoradiotherapy.

AIM: We investigated blood parameters in patients with inoperable stage III non-small cell lung cancer (NSCLC) to predict individual outcomes after definitive chemoradiotherapy (CRT). PATIENTS AND METHODS: Blood parameters of consecutive patients undergoing definitive CRT between 2010 and 2016 for inoperable stage III NSCLC before multimodal treatment and at first follow-up were measured and analyzed. RESULTS: Blood parameters from 99 patients were evaluated. Histologically, about 50% of patients had an adenocarcinoma. All patients received platinum-based sequential or concurrent CRT. The median total dose to the primary tumor was 60 (range=48-70) Gy. On multivariate analysis after adjustment for all co-founders, median overall survival for pre-treatment cutoffs were: lactate dehydrogenase (LDH) >250 U/l was 17 vs. 27 months [hazard ratio (HR)=2.05, 95% confidence intervaI (CI)=1.15-3.66; p=0.015], thrombocytosis >400×106/l: 11 vs. 23 months (HR=2.75, 95% CI=1.1-6.88; p=0.03), hypoalbuminemia <3.5 g/dl: 12 vs. 24 months (HR=2.42, 95% CI=1.21-4.84; p=0.013) and post-treatment neutrophilia >7×106/l: 12 vs. 27 months (HR=2.5, 95% CI=1.21-5.17; p=0.013). CONCLUSION: Pre-treatment elevated LDH, thrombocytosis, hypoalbuminemia and post-treatment neutrophilia were associated with significantly worse overall survival in patients with inoperable stage III NSCLC treated with CRT. Patients with both pre-therapeutic elevated LDH and hypoalbuminemia demonstrated a dismal prognosis despite completion of multimodal treatment.

Pattern-of-failure and salvage treatment analysis after chemoradiotherapy for inoperable stage III non-small cell lung cancer.

BACKGROUND: Loco-regional and distant failure are common in inoperable stage III non small-cell lung cancer (NSCLC) after chemoradiotherapy (CRT). However, there is limited real-world data on failure pattern, patient prognosis and salvage options. METHODS: We analysed 99 consecutive patients with inoperable stage III NSCLC treated with CRT between 2011 and 2016. Follow up CT scans from date of the first-site failure were matched with the delivered radiation treatment plans. Intra-thoracic loco-regional relapse was defined as in-field (IFR) vs. out-of-field recurrence (OFR) [in- vs. outside 50Gy isodose line in the involved lung], respectively. Extracranial distant (DMs) and brain metastases (BMs) as first site of recurrence were also evaluated. Using the Kaplan-Meier method, impact of salvage surgery (sS), radiotherapy (sRT), chemotherapy (sCT) and immunotherapy (sIO) on patient survival was assessed. RESULTS: Median follow-up was 60.0 months. Median PFS from the end of CRT for the entire cohort was 7.5 (95% CI: 6.0-9.0 months) months. Twenty-six (26%) and 25 (25%) patients developed IFR and OFR. Median time to diagnosis of IFR and OFR was 7.2 and 6.2 months. In the entire cohort, onset of IFR and OFR did not influence patient outcome. However, in 73 (74%) patients who survived longer than 12 months after initial diagnosis, IFR was a significant negative prognostic factor with a median survival of 19.3 vs 40.0 months (p < 0.001). No patients with IFR underwent sS and/or sRT. 18 (70%) and 5 (19%) patients with IFR underwent sCT and sIO. Three (12%) patients with OFR underwent sS and are still alive with 3-year survival rate of 100%. 5 (20%) patients with OFR underwent sRT with a median survival of 71.2 vs 19.1 months (p = 0.014). Four (16%) patients with OFR received sIO with a numerical survival benefit (64.6 vs. 26.4 months, p = 0.222). DMs and BMs were detected in 27 (27%) and 16 (16%) patients after median time of 5.8 and 5.13 months. Both had no impact on patient outcome in the entire cohort. However, patients with more than three BMs showed significantly poor OS (9.3 vs 26.0 months; p = 0.012). CONCLUSIONS: After completion of CRT, IFR was a negative prognostic factor in those patients, who survived longer than 12 months after initial diagnosis. Patients with OFR benefit significantly from salvage local treatment. Patients with more than three BMs as first site of failure had a significantly inferior outcome.

Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis.

BACKGROUND: There is limited data on the use of targeted or immunotherapy (TT/IT) in combination with single fraction stereotactic radiosurgery (SRS) in patients with melanoma brain metastasis (MBM). Therefore, we analyzed the outcome and toxicity of SRS alone compared to SRS in combination with TT/IT. METHODS: Patients with MBM treated with single session SRS at our department between 2014 and 2017 with a minimum follow-up of 3 months after first SRS were included. The primary endpoint of this study was local control (LC). Secondary endpoints were distant intracranial control, radiation necrosis-free survival (RNFS), and overall survival (OS). The local/ distant intracranial control rates, RNFS and OS were analyzed using the Kaplan-Meier method. The log-rank test was used to test differences between groups. Cox proportional hazard model was performed for univariate continuous variables and multivariate analyses. RESULTS: Twenty-eight patients (17 male and 11 female) with 52 SRS-lesions were included. The median follow-up was 19 months (range 14-24 months) after first SRS. Thirty-six lesions (69.2%) were treated with TT/IT simultaneously (4 weeks before and 4 weeks after SRS), while 16 lesions (30.8%) were treated with SRS alone or with sequential TT/IT. The 1-year local control rate was 100 and 83.3% for SRS with TT/IT and SRS alone (p = 0.023), respectively. The estimated 1-year RNFS was 90.0 and 82.1% for SRS in combination with TT/IT and SRS alone (p = 0.935). The distant intracranial control rate after 1 year was 47.7 and 50% for SRS in combination with TT/IT and SRS alone (p = 0.933). On univariate analysis, the diagnosis-specific Graded Prognostic Assessment including the BRAF status (Melanoma-molGPA) was associated with a significantly improved LC. Neither gender nor SRS-PTV margin had a prognostic impact on LC. V10 and V12 were significantly associated with RNFS (p < 0.001 and p = 0.004). CONCLUSION: SRS with simultaneous TT/IT significantly improved LC with no significant difference in radiation necrosis rate. The therapy combination appears to be effective and safe. However, prospective studies on SRS with simultaneous TT/IT are necessary and ongoing. TRIAL REGISTRATION: The institutional review board approved this analysis on 10th of February 2015 and all patients signed informed consent (UE nr. 128-14).

Maximum standardized uptake value of primary tumor (SUVmax_PT) and horizontal range between two most distant PET-positive lymph nodes predict patient outcome in inoperable stage III NSCLC patients after chemoradiotherapy.

BACKGROUND: 18F-FDG-positron emission tomography (PET)/computed tomography (CT) is a standard for initial staging in patients with locally advanced stage III non-small cell lung cancer (NSCLC). We evaluated a PET/CT staging score to characterize disease extension and patient outcome in this disease. METHODS: Ninety-nine consecutive patients with NSCLC stage IIIA-B (UICC 7th edition), who underwent 18F-FDG-PET/CT before the start of chemoradiotherapy (CRT) were analyzed. Maximum standardized uptake value of primary tumor (SUVmax_PT) and range between two most distant PET-positive (SUV ≥2.5) lymph nodes in two directions were analyzed for their correlation with patient outcome. The vertical distance was defined as A- and the horizontal as a B-line. RESULTS: According to the results of univariate analysis, score included the SUVmax_PT and horizontal B-line, patients were divided into three risk subgroups: low, intermediate and high-risk subgroups. Subgroups were defined as SUVmax_PT <8 and B-line <3.7 cm, SUVmax_PT >8 or B-line >3.7 cm and SUVmax_PT >8 plus B-line >3.7 cm, respectively. Twenty-eight (28%), 45 (46%) and 26 (26%) patients were assigned to the low, intermediate and high-risk subgroup, respectively. Median event-free survival (EFS) in low, intermediate and high-risk subgroups was 16 (95% CI: 7-25), 13 (95% CI: 12-15) and 10 (95% CI: 7-13) months (P=0.002, log-rank test). Median OS in the low, intermediate and high-risk subgroups was 40 (95% CI: 11-69), 23 (95% CI: 15-31) and 14 (95% CI: 13-14) months (P=0.0001, log-rank test). In the multivariate analysis, SUV, B-line and PET/CT score were significantly associated with EFS [harard ratio (HR) 2.12 (95% CI: 1.27-3.55) and intermediate risk HR 2.01 (95% CI: 1.13-3.59), P=0.003] and OS [high-risk HR 2.79 (95% CI: 1.16-4.55) and intermediate risk HR 2.30 (95% CI: 1.58-4.94), P=0.001]. CONCLUSIONS: A PET/CT score was developed for inoperable stage III NSCLC patients treated with CRT and was an independent predictor of patient outcome in the single-center cohort.