Physician reported toxicities and patient reported quality of life of transperineal ultrasound-guided radiotherapy of prostate cancer.

Purpose: This study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). Methods: Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. Results: In this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8-169 ng/ml). At the median follow-up of 19 months (3-82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. Conclusion: The outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Prognostic significance of pretreatment PET parameters in inoperable, node-positive NSCLC patients with poor prognostic factors undergoing hypofractionated radiotherapy: a single-institution retrospective study.

BACKGROUND: Node-positive non-small cell lung cancers (NSCLCs) present a challenge for treatment decisions, particularly in patients ineligible for concurrent chemoradiotherapy (CRT) due to poor performance status and compromised lung function. We aimed to investigate the prognostic value of pretreatment positron emission tomography (PET) parameters in high-risk patients undergoing hypofractionated radiotherapy. METHODS: A retrospective analysis was conducted on 42 consecutive patients with inoperable node-positive NSCLC, who underwent hypofractionated radiotherapy between 2014 and 2021 at a single institution. Clinical, treatment-related, and [18F]FDG PET-based parameters were correlated with progression-free survival (PFS) and overall survival (OS). Median dichotomisation was performed to establish risk groups. Statistical analyses included univariable and multivariable Cox regression and Kaplan-Meier survival analyses. RESULTS: After a median follow-up of 47.1 months (range: 0.5-101.7), the median PFS and OS were 11.5 months (95% CI: 7.4-22.0), and 24.3 months (95% CI: 14.1-31.8). In univariable Cox regression analysis, significant predictors of PFS included receipt of salvage systemic treatment (p=0.007), SUVmax (p=0.032), and tMTV (p=0.038). Similarly, ECOG-PS (p=0.014), Histology (p=0.046), and tMTV (p=0.028) were significant predictors of OS. Multivariable Cox regression analysis (MVA) identified SUVmax as a significant predictor for PFS [HR: 2.29 (95% CI: 1.02-5.15); p=0.044]. For OS, ECOG-PS remained a significant prognosticator [HR: 3.53 (95% CI: 1.49-8.39); p=0.004], and tMTV approached significance [HR: 2.24 (95% CI: 0.95-5.26); p=0.065]. Furthermore, the high tMTV group exhibited a median PFS of 5.3 months [95% CI: 2.8-10.4], while the low tMTV group had a PFS of 15.2 months [95% CI: 10.1-33.5] (p=0.038, log-rank test). Median OS was 33.5 months [95% CI: 18.3-56.8] for tMTV ≤ 36.6 ml vs. 14.1 months [95% CI: 8.1-27.2] for tMTV > 36.6 ml (p=0.028, log-rank test). CONCLUSION: Pretreatment PET parameters, especially tMTV, hold promise as prognostic indicators in NSCLC patients undergoing hypofractionated radiotherapy. The study highlights the potential of PET metrics as biomarkers for patient stratification.

Timing of stereotactic radiosurgery within the first-line systemic treatment in non-small cell lung cancer brain metastases: a retrospective single-center cohort study.

Background: Stereotactic radiosurgery/radiotherapy (SRS/SRT) and novel systemic treatments, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), have demonstrated to be effective in managing brain metastases in non-small cell lung cancer (NSCLC). However, the optimal treatment sequence of SRS/SRT and TKI/ICI remains uncertain. This retrospective monocentric analysis addresses this question by comparing the outcomes of patients with NSCLC brain metastases who received upfront SRS/SRT versus those who were initially treated with TKI/ICI. Methods: All patients treated with SRS/SRT and TKI/ICI for NSCLC brain metastases were collected from a clinical database. The patients who received first-line TKI or ICI for the treatment of brain metastases were then selected for further analysis. Within this cohort, a comparative analysis between upfront SRS/SRT and patients initially treated with TKI/ICI was conducted, assessing key parameters such as overall survival (OS), intracranial progression-free survival (iPFS) and treatment-related toxicity. Both OS and iPFS were defined as the time from SRS/SRT to either death or disease progression, respectively. Results: The analysis encompassed 54 patients, of which 34 (63.0%) patients received SRS/SRT and TKI/ICI as their first-line therapy. Of the latter, 17 (50.0%) patients received upfront SRS/SRT and 17 (50.0%) were initially treated with TKI/ICI; 24 (70.6%) received SRS/SRT and ICI, and 10 (29.4%) received SRS/SRT and TKI. The cohorts did not significantly differ in the univariable analyses for the following parameters: sex, age, histology, molecular genetics, disease stage at study treatment, performance status, number of brain metastases, treatment technique, tumor volume, target volume, disease progression, radiation necrosis, dosimetry. While no significant differences were found in terms of iPFS and OS between patients treated with upfront SRS/SRT and patients initially treated with TKI, upfront SRS/SRT demonstrated significantly superior OS when compared to patients initially treated with ICI (median OS not reached vs. 17.5 months; mean 37.8 vs. 23.6 months; P=0.03) with no difference in iPFS. No significant differences in treatment-related toxicity were observed among the cohorts. Conclusions: In this retrospective, single-center cohort study, patients treated with upfront SRS/SRT demonstrated significantly longer OS compared to patients initially treated with ICI in the cohort receiving first-line therapy for brain metastases. However, given the retrospective design and the limited cohort size, definitive conclusions cannot be drawn from these findings. Nevertheless, the results suggest that the timing of SRS/SRT may play an important role in treatment outcomes. Further investigation, preferably through prospective randomized trials, is warranted to provide more conclusive answers to this important question.

Perioperative Predictive Factors for Tumor Regression and Survival in Non-Small Cell Lung Cancer Patients Undergoing Neoadjuvant Treatment and Lung Resection.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into a lung adenocarcinoma group (LUAD) and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small-cell lung cancer were included in the study. A total of 58 (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Additionally, 9 (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III, respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7 cm), and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR [95% confidence interval, p-value] of 6.88 [2.40-19.77, p < 0.0001], 3.13 [1.11-8.83, p = 0.0310], and 3.76 [1.20-11.81, p = 0.0233], respectively). Age > 70 years, extended resection > one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Case report: Incidental MALT lymphoma of the left adrenal gland mimicking a metastatic spread within durvalumab maintenance treatment in inoperable stage III non-small cell lung cancer.

Durvalumab after chemotherapy in non-operable stage III non-small cell lung cancer (NSCLC) is the standard of care worldwide. We present a patient with the incidental discovery of a unilateral MALT lymphoma of the adrenal gland and adrenalitis during durvalumab maintenance treatment detected by 18F-FDG-PET/CT. We assessed the clinical and histopathological findings, radiological examinations and overall treatment. Our work emphasizes the significance of considering other differential diagnoses and the importance of multidisciplinary treatment of the findings, especially within clinical trials.

The role of online MR-guided multi-fraction stereotactic ablative radiotherapy in lung tumours.

Background: The aim of this prospective observational study was to evaluate the dosimetry benefits, changes in pulmonary function, and clinical outcome of online adaptive MR-guided SBRT. Methods: From 11/2020-07/2022, 45 consecutive patients with 59 lesions underwent multi-fraction SBRT (3-8 fractions) at our institution. Patients were eligible if they had biopsy-proven NSCLC or lung cancer/metastases diagnosed via clinical imaging. Endpoints were local control (LC) and overall survival (OS). We evaluated PTV/GTV dose coverage, organs at risk exposure, and changes in pulmonary function (PF). Acute toxicity was classified per the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Results: The median PTV was 14.4 cm3 (range: 3.4 - 96.5 cm3). In total 195/215 (91%) plans were reoptimised. In the reoptimised vs. predicted plans, PTV coverage by the prescribed dose increased in 94.6% of all fractions with a median increase in PTV VPD of 5.6% (range: -1.8 - 44.6%, p < 0.001), increasing the number of fractions with PTV VPD ≥ 95% from 33% to 98%. The PTV D95% and D98% (BED10) increased in 93% and 95% of all fractions with a median increase of 7.7% (p < 0.001) and 10.6% (p < 0.001). The PTV D95% (BED10) increased by a mean of 9.6 Gy (SD: 10.3 Gy, p < 0.001). At a median follow-up of 21.4 months (95% CI: 12.3-27.0 months), 1- and 2-year LC rates were 94.8% (95% CI: 87.6 - 100.0%) and 91.1% (95% CI: 81.3 - 100%); 1- and 2-year OS rates were 85.6% (95% CI: 75.0 - 96.3%) and 67.1 % (95% CI: 50.3 - 83.8%). One grade ≥ 3 toxicity and no significant reduction in short-term PF parameters were recorded. Conclusions: Online adaptive MR-guided SBRT is an effective, safe and generally well tolerated treatment option for lung tumours achieving encouraging local control rates with significantly improved target volume coverage.

Simultaneous object detection and segmentation for patient-specific markerless lung tumor tracking in simulated radiographs with deep learning.

BACKGROUND: Real-time tumor tracking is one motion management method to address motion-induced uncertainty. To date, fiducial markers are often required to reliably track lung tumors with X-ray imaging, which carries risks of complications and leads to prolonged treatment time. A markerless tracking approach is thus desirable. Deep learning-based approaches have shown promise for markerless tracking, but systematic evaluation and procedures to investigate applicability in individual cases are missing. Moreover, few efforts have been made to provide bounding box prediction and mask segmentation simultaneously, which could allow either rigid or deformable multi-leaf collimator tracking. PURPOSE: The purpose of this study was to implement a deep learning-based markerless lung tumor tracking model exploiting patient-specific training which outputs both a bounding box and a mask segmentation simultaneously. We also aimed to compare the two kinds of predictions and to implement a specific procedure to understand the feasibility of markerless tracking on individual cases. METHODS: We first trained a Retina U-Net baseline model on digitally reconstructed radiographs (DRRs) generated from a public dataset containing 875 CT scans and corresponding lung nodule annotations. Afterwards, we used an independent cohort of 97 lung patients to develop a patient-specific refinement procedure. In order to determine the optimal hyperparameters for automatic patient-specific training, we selected 13 patients for validation where the baseline model predicted a bounding box on planning CT (PCT)-DRR with intersection over union (IoU) with the ground-truth higher than 0.7. The final test set contained the remaining 84 patients with varying PCT-DRR IoU. For each testing patient, the baseline model was refined on the PCT-DRR to generate a patient-specific model, which was then tested on a separate 10-phase 4DCT-DRR to mimic the intrafraction motion during treatment. A template matching algorithm served as benchmark model. The testing results were evaluated by four metrics: the center of mass (COM) error and the Dice similarity coefficient (DSC) for segmentation masks, and the center of box (COB) error and the DSC for bounding box detections. Performance was compared to the benchmark model including statistical testing for significance. RESULTS: A PCT-DRR IoU value of 0.2 was shown to be the threshold dividing inconsistent (68%) and consistent (100%) success (defined as mean bounding box DSC > 0.6) of PS models on 4DCT-DRRs. Thirty-seven out of the eighty-four testing cases had a PCT-DRR IoU above 0.2. For these 37 cases, the mean COM error was 2.6 mm, the mean segmentation DSC was 0.78, the mean COB error was 2.7 mm, and the mean box DSC was 0.83. Including the validation cases, the model was applicable to 50 out of 97 patients when using the PCT-DRR IoU threshold of 0.2. The inference time per frame was 170 ms. The model outperformed the benchmark model on all metrics, and the comparison was significant (p < 0.001) over the 37 PCT-DRR IoU > 0.2 cases, but not over the undifferentiated 84 testing cases. CONCLUSIONS: The implemented patient-specific refinement approach based on a pre-trained baseline model was shown to be applicable to markerless tumor tracking in simulated radiographs for lung cases.

First-site-metastasis pattern in patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with or without immune check-point inhibition: a retrospective analysis.

PURPOSE: The aim of this study was to investigate a first-site-metastasis pattern (FSMP) in unresectable stage III NSCLC after concurrent chemoradiotherapy (cCRT) with or without immune checkpoint inhibition (ICI). METHODS: We defined three patient subgroups according to the year of initial multimodal treatment: A (2011-2014), B (2015-2017) and C (2018-2020). Different treatment-related parameters were analyzed. Observed outcome parameters were brain metastasis-free survival (BMFS), extracranial distant metastasis-free survival (ecDMFS) and distant metastasis-free survival (DMFS). RESULTS: 136 patients treated between 2011 and 2020 were included with ≥ 60.0 Gy total dose and concurrent chemotherapy (cCRT); thirty-six (26%) received ICI. Median follow-up was 49.7 (range:0.7-126.1), median OS 31.2 (95% CI:16.4-30.3) months (23.4 for non-ICI vs not reached for ICI patients, p = 0.001). Median BMFS/ecDMFS/DMFS in subgroups A, B and C was 14.9/16.3/14.7 months, 20.6/12.9/12.7 months and not reached (NR)/NR/36.4 months (p = 0.004/0.001/0.016). For cCRT+ICI median BMFS was 53.1 vs. 19.1 months for cCRT alone (p = 0.005). Median ecDMFS achieved 55.2 vs. 17.9 (p = 0.003) and median DMFS 29.5 (95% CI: 1.4-57.6) vs 14.93 (95% CI:10.8-19.0) months (p = 0.031), respectively. Multivariate analysis showed that age over 65 (HR:1.629; p = 0.036), GTV ≥ 78 cc (HR: 2.100; p = 0.002) and V20 ≥ 30 (HR: 2.400; p = 0.002) were negative prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS (HR: 1.739; p = 0.027). After onset of brain metastasis (BM), patients survived 13.3 (95% CI: 6.4-20.2) months and 8.6 months (95% CI: 1.6-15.5) after extracranial-distant-metastasis (ecDM). Patients with ecDM as FSMP reached significantly worse overall survival of 22.1 (range:14.4-29.8) vs. 40.1 (range:18.7-61.3) months (p = 0.034) in the rest of cohort. In contrast, BM as FSMP had no impact on OS. CONCLUSION: This retrospective analysis of inoperable stage III NSCLC patients revealed that age over 65, V20 ≥ 30 and GTV ≥ 78 cc were prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS. ICI treatment led to a significant improvement of BMFS, ecDMFS and DMFS. ecDM as FSMP was associated with significant deterioration of OS, whereas BM as FSMP was not.

Early mortality in German patients with lung cancer: risk factors associated with 30-and 60-day mortality.

Despite therapeutic advances, early mortality in lung cancer is still prevalent. In this study, we aimed to assess risk factors for 30- and 60-day mortality in German lung cancer patients. In this retrospective cross-sectional analysis, we used data of lung cancer patients treated at LMU Hospital Munich between 2015 and 2019. We categorized patients into 30-day mortality, 60 day-mortality, and longer survival. We used Student's t-test and ANOVA to compare means and Chi2-test to compare frequencies. We used logistic regression analysis to identify factors associated with a risk for early mortality. Of the 2454 lung cancer patients, 2.0% (n = 50) died within 30 and 1.7% (n = 41) within 30 to 60 days of diagnosis. Older age and advanced stage at diagnosis were significantly associated with early mortality in the univariate and the multivariate analysis. Patients in the 30-day mortality group significantly more often did not receive tumor-directed therapy. They were also more likely to die in an acute care setting compared to the 60-day mortality group. The group of patients who died unexpectedly (12.0%) was dominantly female, with a high proportion of patients with unintentional weight loss at the time of diagnosis. Our results suggest that in the treatment of patients with lung cancer there is a need for a greater focus on older patients. Moreover, physicians should pay special attention to females with recent weight loss and patients with a comorbidity of diabetes mellitus or renal impairment. Engaging a case manager focused on detecting patients with the above characteristics could help improve overall care.

Guideline adherence of tumor board recommendations in lung cancer and transfer into clinical practice.

PURPOSE: Evaluating patients and treatment decisions in a multidisciplinary tumor board has led to better quality of care and longer survival in cancer patients. The aim of this study was to evaluate tumor board recommendations for thoracic oncology patients regarding guideline adherence and transferal of recommendations into clinical practice. METHODS: We evaluated tumor board recommendations of the thoracic oncology tumor board at Ludwig-Maximilians University (LMU) Hospital Munich between 2014 and 2016. We compared patient characteristics between guideline-adherent and non-guideline-adherent recommendations, as well as between transferred and non-transferred recommendations. We used multivariate logistic regression models to evaluate factors associated with guideline adherence. RESULTS: Over 90% of recommendations by the tumor board were either adherent to the guidelines (75.5%) or over fulfilling guidelines (15.6%). Almost 90% of recommendations were transferred to clinical practice. If a recommendation was not according to the guidelines, the reason was mostly associated with the general condition (age, Charlson comorbidity index, ECOG) of the patient or due to the patients' request. Surprisingly, sex also had a significant influence on the guideline adherence of recommendations, with females being more likely to get recommendations not according to the guidelines. CONCLUSION: In conclusion, the results of this study are promising, as the guideline adherence of recommendations as well as the transferal of recommendations into clinical practice were high. In the future, a special focus should be put on fragile patients as well as female patients.

Histology of the Primary Tumor Correlates with False Positivity of Integrated 18F-FDG-PET/CT Lymph Node Staging in Resectable Lung Cancer Patients.

This study aimed to evaluate the diagnostic accuracy and false positivity rate of lymph node (LN) staging assessed by integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in patients with operable lung cancer to the tumor histology. In total, 129 consecutive patients with non-small-cell lung cancer (NSCLC) undergoing anatomical lung resections were included. Preoperative LN staging was evaluated in the relationship to the histology of the resected specimens (group 1: lung adenocarcinoma/LUAD; group 2: squamous cell carcinoma/SQCA). Statistical analysis was performed by the Mann-Whitney U-test, the chi2 test, and binary logistic regression analysis. To establish an easy-to-use algorithm for the identification of LN false positivity, a decision tree including clinically meaningful parameters was generated. In total, 77 (59.7%) and 52 (40.3%) patients were included in the LUAD and SQCA groups, respectively. SQCA histology, non-G1 tumors, and tumor SUVmax > 12.65 were identified as independent predictors of LN false positivity in the preoperative staging. The corresponding ORs and their 95% CIs were 3.35 [1.10-10.22], p = 0.0339; 4.60 [1.06-19.94], p = 0.0412; and 2.76 [1.01-7.55], and p = 0.0483. The preoperative identification of false-positive LNs is an important aspect of the treatment regimen for patients with operable lung cancer; thus, these preliminary findings should be further evaluated in larger patient cohorts.

Positron Emission Tomography/Computed Tomography (PET/CT)-Based, Local Consolidative Radiotherapy after Chemoimmunotherapy in Metastatic, Non-Oncogene-Addicted Non-Small-Cell Lung Cancer (NSCLC).

The optimal sequence of chemo/immuno- and radiotherapy (RT) in metastatic non-small-cell lung cancer (NSCLC) remains challenging. Here, we describe the case of a 58-year-old female patient with an initially metastasized NSCLC obtaining local and distance durable response after chemo-immunotherapy and local RT associated with immunotherapy maintenance. Our experience offers a valuable perspective in choosing how to combine therapies to ensure the longest possible response in patients with estimated poor prognosis.

Finger Pain as an Uncommon Primary Manifestation of Lung Carcinoma.

A 54-year-old patient presented with progressive pain for one month in the second finger of the right hand with an emphasis on the proximal interphalangeal (PIP) joint. Subsequent magnetic resonance imaging (MRI) showed a diffuse intraosseous lesion at the base of the middle phalanx with destruction of the cortical bone and extraosseous soft tissue. An expansively growing chondromatous bone tumor, e.g., a chondrosarcoma, was suspected. After incisional biopsy, the pathologic findings finally revealed, surprisingly, a metastasis of a poorly differentiated non-small cell adenocarcinoma of the lung. This case illustrates a rare but important differential diagnosis for painful finger lesions.

Metabolic patterns on [18F]FDG PET/CT in patients with unresectable stage III NSCLC undergoing chemoradiotherapy ± durvalumab maintenance treatment.

PURPOSE: In patients with unresectable stage III non-small-cell lung cancer (NSCLC), durvalumab maintenance treatment after chemoradiotherapy (CRT) significantly improves survival. So far, however, metabolic changes of tumoral lesions and secondary lymphoid organs under durvalumab are unknown. Hence, we assessed changes on [18F]FDG PET/CT in comparison to patients undergoing CRT alone. METHODS: Forty-three patients with [18F]FDG PET/CT both before and after standard CRT for unresectable stage III NSCLC were included, in 16/43 patients durvalumab maintenance treatment was initiated (CRT-IO) prior to the second PET/CT. Uptake of tumor sites and secondary lymphoid organs was compared between CRT and CRT-IO. Also, readers were blinded for durvalumab administration and reviewed scans for findings suspicious for immunotherapy-related adverse events (irAE). RESULTS: Initial uptake characteristics were comparable. However, under durvalumab, diverging metabolic patterns were noted: There was a significantly higher reduction of tumoral uptake intensity in CRT-IO compared to CRT, e.g. median decrease of SUVmax -70.0% vs. -24.8%, p = 0.009. In contrast, the spleen uptake increased in CRT-IO while it dropped in CRT (median + 12.5% vs. -4.4%, p = 0.029). Overall survival was significantly longer in CRT-IO compared to CRT with few events (progression/death) noted in CRT-IO. Findings suggestive of irAE were present on PET/CT more often in CRT-IO (12/16) compared to CRT (8/27 patients), p = 0.005. CONCLUSION: Durvalumab maintenance treatment after CRT leads to diverging tumoral metabolic changes, but also increases splenic metabolism and leads to a higher proportion of findings suggestive of irAE compared to patients without durvalumab. Due to significantly prolonged survival with durvalumab, survival analysis will be substantiated in correlation to metabolic changes as soon as more clinical events are present.

Concurrent/sequential versus sequential immune checkpoint inhibition in inoperable large stage III non-small cell lung cancer patients treated with chemoradiotherapy: a prospective observational study.

PURPOSE/AIM: The international standard for patients with large inoperable stage III NSCLC is durvalumab consolidation after concurrent chemoradiotherapy (CRT). In this single centre observational study based on individual data, we prospectively evaluated the role of concurrent/sequential versus sequential immune checkpoint inhibition (ICI). METHODS AND PATIENTS: In total, 39 stage III NSCLC patients were prospectively enrolled, 11 (28%) patients were treated with simultaneous and consolidation therapy with PD-1 inhibition (nivolumab) (SIM-cohort) and 28 (72%) patients received PD-L1 inhibition (durvalumab) as consolidation treatment up to 12 months after the end of CRT (SEQ-cohort). RESULTS: For the entire cohort, median progression-free survival (PFS) was 26.3 months and median survival (OS), locoregional recurrence-free survival and distant metastasis-free survival were not reached. For the SIM-cohort, median OS was not reached and PFS was 22.8 months, respectively. In the SEQ-cohort, neither median PFS nor OS were reached. After propensity score matching, PFS at 12/24 months were 82/44% in the SIM-cohort and 57/57% in the SEQ-cohort (p = 0.714), respectively. In the SIM-cohort, 36.4/18.2% of patients showed grade II/III pneumonitis; in the SEQ-cohort 18.2/13.6% after PSM (p = 0.258, p = 0.55). CONCLUSION: Both concurrent/sequential and sequential ICI show a favorable side effect profile and promising survival in treated patients with inoperable large stage III NSCLC. Concurrent ICI showed a numerical non-significant improvement regarding 6- and 12-months PFS and distant control compared to sequential approach in this small study. However, concurrent ICI to CRT was associated with a non-significant moderate increase in grade II/III pneumonitis.

Preoperative Hilar and Mediastinal Lymph Node Staging in Patients with Suspected or Diagnosed Lung Cancer: Accuracy of 18F-FDG-PET/CT:A Retrospective Cohort Study of 138 Patients.

The aim of this study was to evaluate the diagnostic accuracy of integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of suspected or proven lung cancer, and to investigate potential risk factors for false negative and false positive HMLN metastases. We retrospectively analyzed 162 consecutive patients with suspected or pathologically proven non-small cell lung cancer (NSCLC). The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficacy of 18F-FDG-PET/CT. Univariate and multivariate analyses were conducted to detect risk factors of false positives and false negatives. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of integrated 18F-FDG-PET/CT in detecting HMLN metastases were 59.1% (26/44), 69.1% (65/94), 47.3% (26/55), 78.3% (65/83), and 65.9% (91/138), respectively. The ROC curve showed an area under the curve (AUC) of 0.625 (95%-CI 0.468-0.782). The incidence of false negative and false positive HMLN metastases was 21.7% (18/83) and 52.7% (29/55), respectively. Our data shows that integrated 18F-FDG-PET/CT staging provides lower specificity and sensitivity. This confirms the ESTS guideline on lymph node staging for PET-positive HMLN. Yet it advocates more invasive staging even for PET-negative HMLN.

Five years after PACIFIC: update on multimodal treatment efficacy based on real-world reports.

INTRODUCTION: The growing body of real-life data on maintenance treatment with durvalumab suggests that immunological markers of the cancer host interplay may have significant effects on the efficacy of multimodal therapy in patients with unresectable stage III NSCLC. AREAS COVERED: We summarize real-world clinical data regarding this new tri-modal approach and report on potential biomarker landscape. EXPERT OPINION: The obvious question posed in this context of a very heterogeneous inoperable stage III NSCLC disease is: How can we augment an ability to predict checkpoint inhibition success or failure? Which tools and biomarkers, which clinical metadata and genetic background are relevant and feasible? No single biomarker will ever fully dominate the unresectable stage III NSCLC space, so we advocate multilevel and multivariate analysis of biomarkers. In this particular opinion piece, we explore the impact of PD-L1 expression on tumor cells, neutrophil-to-lymphocyte ratio, EGFR and STK11 mutational status, interferon-gamma signature, and tumor-infiltrating lymphocytes among others.

Comparison of the sensitivity of different criteria to select lung cancer patients for screening in a cohort of German patients.

INTRODUCTION: Trials of CT-based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population. METHODS: We used data from 3623 lung cancer patients from the data warehouse of the German Center for Lung Research (DZL). We compared the sensitivity of the following lung cancer screening criteria overall and stratified by age and histology: the National Lung Screening Trial (NLST), the Danish Lung Cancer Screening Trial (DLCST), the 2013 and 2021 US Preventive Services Task Force (USPSTF), and an adapted version of the Prostate, Lung, Colorectal, and Ovarian no race model (adapted PLCOm2012) with 6-year risk thresholds of 1.0%/6 year and 1.7%/6 year. RESULTS: Overall, the adapted PLCOm2012 model (1%/6 years), selected the highest proportion of lung cancer patients for screening (72.4%), followed by the 2021 USPSTF (70.0%), the adapted PLCOm2012 (1.7%/6 year) (57.4%), the 2013 USPTF (57.0%), DLCST criteria (48.7%), and the NLST (48.5%). The adapted PLCOm2012 risk model (1.0%/6 year) had the highest sensitivity for all histological types except for small-cell and large-cell carcinomas (non-significant), whereas the 2021 USPTF selected a higher proportion of patients. The sensitivity levels were higher in males than in females. CONCLUSION: Using a risk-based selection score resulted in higher sensitivities compared to criteria using dichotomized age and smoking history. However, gender disparities were apparent in all studied eligibility criteria. In light of increasing lung cancer incidences in women, all selection criteria should be reviewed for ways to close this gender gap, especially when implementing a large-scale lung cancer screening program.

Stereotactic radiosurgery and combined immune checkpoint therapy with ipilimumab and nivolumab in patients with melanoma brain metastases: A retrospective monocentric toxicity analysis.

Purpose and objective: Adding stereotactic radiosurgery (SRS) to combined immune checkpoint therapy with ipilimumab and nivolumab (IPI + NIVO) has led to promising results for patients with melanoma brain metastases (MBM). This study retrospectively analyzes the toxicity profile depending on the timing of SRS with regard to IPI + NIVO. Materials and methods: For this study, the clinical database was searched for all patients with MBM who were treated with SRS and IPI + NIVO. The patients were separated into three groups: group A completed IPI + NIVO (usually up to four cycles) >14 days before SRS, in group B IPI + NIVO was initiated>14 days after SRS, and group C received SRS concurrently to IPI + NIVO. Treatment related toxicity was obtained from clinical and neuroradiological records. Analyses were performed using the Fisher-Yates-test. Results: 31 patients were assessed including six (19.4 %), seven (22.6 %) and 18 (58.1 %) patients, in groups A, B and C, respectively. Baseline prognostic markers between groups were balanced. In total, five (16.1 %) patients experienced neurological grade 3 toxicities related to SRS. All of these five patients were in group C, which was near-significantly correlated with a risk for grade 3 toxicities (p = 0.058). Post-hoc analyses showed that a maximum time period of seven days between SRS and IPI + NIVO was significantly correlated with grade 3 toxicity (p = 0.048). Conclusion: Application of SRS to IPI + NIVO within a seven-day span was related to higher toxicity rates in this retrospective analysis. After previous studies focused on immune checkpoint monotherapies with SRS and declared it as safe, this study indicates that concomitant application of IPI + NIVO and SRS might increase side effects. Prospective validation is warranted to corroborate these findings.