Background and objective: A combined approach of magnetic resonance imaging (MRI) targeted biopsies (TBx) and systematic biopsies (SBx) was recommended previously in patients with unilateral suspicious prostate cancer (PCa) on MRI. Yet, new PCa guidelines suggest that contralateral SBx can be omitted. It is unknown how this guideline modification impacts treatment selection. This study evaluates the value of contralateral SBx in radiation treatment selection in patients with unilateral suspicious lesions (Prostate Imaging Reporting and Data System [PIRADS] >= 3) on MRI. Methods: Case files of 80 patients with a unilateral suspicious lesion on diagnostic MRI who underwent TBx and bilateral SBx were collected. The cases were presented to four radiation oncologists twice: once with diagnostic information of bilateral SBx and TBx, and once with diagnostic information of ipsilateral SBx and TBx pathology results. Based on this information, external beam radiation treatment (EBRT) fractionation scheme, duration of androgen deprivation therapy (ADT), and feasibility of brachytherapy (monotherapy or brachyboost) were considered. Key findings and limitations: After omitting information of contralateral SBx pathology results, selection of EBRT fractionation scheme and ADT duration changed in 14% (95% confidence interval [CI] 9.8-17) and 15% (95% CI 11-19) of cases, respectively. The feasibility of brachytherapy as monotherapy and brachyboost, respectively, changed in 11% (95% CI 7.9-15) and in 21% (95% CI 17-26) of cases, with overall poor interobserver variability for both diagnostic scenarios (Fleiss' kappa 0.15 and 0.16). Conclusions and clinical implications: Our findings indicate that omitting contralateral SBx has an impact on the treatment selection of patients who choose for radiation therapy as their treatment for locally confined PCa. Patient summary: In patients with prostate cancer identified via magnetic resonance imaging on one side of the prostate, exclusion of prostate biopsies from the opposite side affected the selection of radiation treatment. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Abstract Introduction: The phase II PERICLES trial investigated the efficacy of atezolizumab (anti-PD-L1) for advanced penile cancer, with or without radiotherapy. As previously published, durable responses (progression-free at 12 months) were observed in 4 out of 32 enrolled patients. Here, we present the final overall survival (OS) results and an analysis of potential biomarkers for immunotherapy response. Methods: Preplanned analysis projected that at 27/32 events, the study would have 80% power (2-sided α=0.05) to assess whether the OS for the entire cohort significantly differed from the hypothesized historical median for stage IV patients. Baseline tumor tissue samples were subjected to bulk-RNA sequencing (n=31), fluorescent (n=28) and chromogenic (n=30) multiplex immunohistochemistry. We quantified the densities of CD3+CD8+ cytotoxic T-cells, CD3+CD8−FoxP3− T-helper cells, CD3+CD8−FoxP3+ regulatory T-cells, CD68+ macrophages and CD20+ B-cells in both the tumor and stromal compartments and assessed spatial relationships. We also quantified CD8+PD1+ (potentially enriched for tumor reactivity) and CD8+PD1− T-cells. Differential expression and gene set enrichment analysis (GSEA) were performed using the hallmarks gene sets. Results: The median OS for the entire study cohort was 11.3 months (95% CI, 5.5-16.7), which is an improvement compared to the hypothesized historical median of 7.8 months for stage IV patients (one sample log-rank p=0.033). Biomarker analyses showed an increased density of stromal macrophages (p<0.001) and intratumoral cytotoxic T-cells (p=0.035) in durable responders compared to non-responders. Additionally, we observed an increased density of intratumoral CD8+PD1+ in durable responders (p<0.001). In contrast, intratumoral CD8+PD1− densities were comparable between durable and non-responders (p=0.057). Patients with a high density of intratumoral CD8+PD1+ also had an improved progression-free survival (PFS) (log-rank, p<0.001) and OS (log-rank, p=0.002). Analysis of the spatial relationships in the tumor microenvironment (TME) showed that durable responders had larger distances between cytotoxic T-cells and T-helper cells (p=0.034). GSEA revealed significant (FDR≤5%) up-regulation of IFN-α/γ responses in durable responders. In contrast, non-responders showed up-regulation of epithelial-mesenchymal transition, KRAS signaling and angiogenesis, suggesting potential barriers to an anti-tumor response. Conclusion: In the final clinical analysis, OS was improved with atezolizumab compared to the historical population of stage IV patients. CD8+PD1+ T-cells, a common proxy for tumor-reactive T-cells, and spatial relationships in the TME might serve as biomarkers of durable response to immunotherapy in advanced penile cancer. Citation Format: Tynisha S. Rafael, Alberto Gil-Jimenez, Hielke M. de Vries, Iris M. Seignette, Elise Bekers, Marta Lopez-Yurda, Dennis Peters, Erik Hooijberg, Annegien Broeks, Oscar R. Brouwer, Eva Schaake, Daniel J. Vis, Tanja D. de Gruijl, Lodewyk F.A. Wessels, Michiel S. van der Heijden. The penile cancer tumor microenvironment and immunotherapy response: Results from the PERICLES trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2488.

PURPOSE:Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti-PD-L1) in patients with advanced penile cancer, with or without radiotherapy (RT). PATIENTS AND METHODS:A single-center, nonrandomized phase II study with two treatment arms was conducted in 32 patients with histologically confirmed advanced penile cancer. All patients received atezolizumab (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit from RT for locoregional disease control, received additional irradiation. The primary end point was 1-year progression-free survival (PFS) for the complete cohort and was reached if the actual 1-year PFS was at least 35%. Secondary end points included OS, objective response rate (ORR), and tolerability. Exploratory biomarker analyses were conducted in pretreatment specimens. RESULTS:Median follow-up was 29.1 months (IQR, 18.1-33.5). Grade 3-4 adverse events related to atezolizumab or RT were observed in 3/32 (9.4%) and 13/20 (65%) patients, respectively. One-year PFS was 12.5% (95% CI, 5.0 to 31.3), which did not meet the study's primary end point. Median OS was 11.3 months (95% CI, 5.5 to 18.7). In the objective response-evaluable population (n = 30; 93.8%), the ORR was 16.7% (95% CI, 6 to 35), including 2 (6.7%) complete responders and 3 (10%) partial responders. Improved PFS was observed in patients with high-risk human papillomavirus (hrHPV)-positive tumors (P = .003) and those with high infiltration of intratumoral CD3+CD8+ T cells (P = .037). CONCLUSION:Although the primary end point of 1-year PFS was not met, durable antitumor activity to atezolizumab was observed in a subset of patients. Biomarkers, such as hrHPV and intratumoral CD3+CD8+ T-cell infiltration, may help to better select responders.

BJU InternationalEarly View Research Communication External validation of nomograms for salvage radiotherapy after radical prostatectomy Oktay Özman, Corresponding Author Oktay Özman ozmanoktay@hotmail.com o.ozman@nki.nl orcid.org/0000-0003-2499-8947 Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Correspondence: Oktay Özman, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. e-mails: ozmanoktay@hotmail.com and o.ozman@nki.nlSearch for more papers by this authorHans Veerman, Hans Veerman orcid.org/0000-0002-2297-8179 Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Prostate Cancer Network, Amsterdam, The NetherlandsSearch for more papers by this authorEva Schaake, Eva Schaake Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The NetherlandsSearch for more papers by this authorHenk van der Poel, Henk van der Poel Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Prostate Cancer Network, Amsterdam, The NetherlandsSearch for more papers by this author Oktay Özman, Corresponding Author Oktay Özman ozmanoktay@hotmail.com o.ozman@nki.nl orcid.org/0000-0003-2499-8947 Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Correspondence: Oktay Özman, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. e-mails: ozmanoktay@hotmail.com and o.ozman@nki.nlSearch for more papers by this authorHans Veerman, Hans Veerman orcid.org/0000-0002-2297-8179 Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Prostate Cancer Network, Amsterdam, The NetherlandsSearch for more papers by this authorEva Schaake, Eva Schaake Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The NetherlandsSearch for more papers by this authorHenk van der Poel, Henk van der Poel Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Prostate Cancer Network, Amsterdam, The NetherlandsSearch for more papers by this author First published: 19 January 2022 https://doi.org/10.1111/bju.15692Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Purpose of review Studies on treatment options for patients with locally advanced vulvar cancer (LAVC) are scarce, and high-level evidence for a primary treatment choice is lacking. Furthermore, current treatment options are associated with extensive morbidity and high complication rates. More effective treatment options are urgently needed. This review describes current treatment possibilities, focusing on literature regarding neoadjuvant chemotherapy (NACT) followed by surgery. Recent findings Although data are heterogeneous and limited, NACT followed by surgery might be an effective and well tolerated treatment alternative associated with lower morbidity compared with current treatment options, such as excenterative surgery or definitive chemoradiation. Summary Up until now, several studies describe an overall response rate of 40–86%. Surgery turned out to be possible in 40–90% of the LAVC patients who received NACT. Prospective studies on the efficacy and safety of NACT followed by surgery with a homogeneous chemotherapy regimen are urgently awaited. NACT should, at this point, still be considered investigational.

Background: Concurrent chemoradiotherapy (CRT) as a definitive treatment option for patients with nonmetastatic muscle-invasive bladder carcinoma (MIBC) is increasingly being applied in clinical practice. Objective: To assess the oncological and toxicity outcomes in a contemporary cohort of nonmetastatic MIBC patients treated with concurrent CRT in daily practice. Design, setting, and participants: Patients with nonmetastatic MIBC (cT2-4aN0M0) who had received CRT with curative intent between January 2010 and April 2020 in three centers were retrospectively identified. The CRT consisted of 66 Gy (or biologically equivalent) plus either mitomycin C and fluorouracil/capecitabine or cisplatinum. Outcome measurements and statistical analysis: The primary endpoint was the 2-yr locoregional disease-free survival (LDFS) estimate. Secondary endpoints were complete response, disease-specific survival (DSS), overall survival (OS), bladder intact event-free survival (BI-EFS), and severe adverse events (<90 d of starting CRT). Kaplan-Meier survival and Cox multivariable regression analyses were performed. Results and limitations: We included data of 240 MIBC patients with a median age of 74 yr and a median follow-up of 27 mo (interquartile range 11–44). Complete response on first cystoscopy after CRT was seen in 209 cases (90%). The 2-yr LDFS was 76% (95% confidence interval [CI] 70–82%); the 5-yr OS and DSS were 50% (95% CI 42–59%) and 70% (95% CI 62–79%), respectively. On multivariable analysis, cT2 versus cT3–4 tumor stage was significantly associated with better DSS (hazard ratio 1.02, 95% CI 1–1.05, p = 0.024). The 2-yr BI-EFS was 75% (95% CI 69–82%). Forty-three (17%) patients experienced a severe adverse event (grade ≥3). Limitations include retrospective design and heterogeneous administration of CRT. Conclusions: Concurrent CRT is a safe and effective treatment modality for nonmetastatic MIBC. Patient summary: Chemoradiotherapy for the treatment of muscle-invasive bladder carcinoma is increasingly being applied. In this study, we reviewed the outcomes of this bladder-sparing treatment using a series of patients treated in three hospitals in daily practice. We found that administration of chemoradiotherapy can be safe and effective.

You have accessJournal of UrologyCME1 May 2022PD22-01 ONCOLOGICAL OUTCOMES OF SENTINEL LYMPH NODE PROCEDURE-GUIDED RADIOTHERAPY VERSUS IMAGING-GUIDED RADIOTHERAPY FOR CLINICALLY LOCALIZED PROSTATE CANCER – A MULTICENTER, RETROSPECTIVE, PROPENSITY SCORE WEIGHTED COMPARISON Hilda de Barros, Nikolaos Grivas, Jan Duin, Daan Mulder, Vincent van der Noort, Arjen Noordzij, Esther Wit, Eva Schaake, Pim van Leeuwen, and Henk van der Poel Hilda de BarrosHilda de Barros More articles by this author , Nikolaos GrivasNikolaos Grivas More articles by this author , Jan DuinJan Duin More articles by this author , Daan MulderDaan Mulder More articles by this author , Vincent van der NoortVincent van der Noort More articles by this author , Arjen NoordzijArjen Noordzij More articles by this author , Esther WitEsther Wit More articles by this author , Eva SchaakeEva Schaake More articles by this author , Pim van LeeuwenPim van Leeuwen More articles by this author , and Henk van der PoelHenk van der Poel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002564.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Insufficient sensitivity of current imaging techniques for nodal staging has led to the exploration of the sentinel lymph node biopsy (SLNB) to select primary prostate cancer (PCa) patients that might benefit from whole-pelvic nodal radiotherapy (WPRT). In this study, we aimed to evaluate oncological outcomes of SLNB-based RT compared to imaging-based RT in cN0M0 PCa patients with an increased estimated risk of nodal metastases. METHODS: This multicenter, retrospective cohort study included 522 cN0 primary PCa patients with a Briganti nomogram-estimated nodal risk >5% treated with external beam RT (EBRT) between 2007-2018. Nodal staging was performed either by radiological staging (261 (50%) patients) or by radiological staging and an additional robot-assisted laparoscopic SLNB (261 (50%) patients). All patients received RT to the prostate and 6 months to 3 years of androgen deprivation therapy (ADT), whereas patients with a histologically positive sentinel node (pN1) also received RT to the pelvic LNs with 3 years of ADT. Endpoints included biochemical recurrence-free survival (BCR-FS) and radiological recurrence-free survival (RR-FS). Propensity score weighted (PSW) multivariable Cox regression analysis was performed to determine independent predictors of BCR and RR. RESULTS: Patients staged with SLNB had a higher rate of extracapsular extension (63% vs 35%, P <0.001) and were at higher risk of nodal metastases (43% vs 29%, P=0.002) compared to imaging-only staged patients. Median follow-up after primary treatment was 64 months (IQR 41-95). In total, 111 patients developed a BCR (SLNB=51, non-SLNB=60) and 98 patients developed a radiological recurrence (SLNB=50, non-SLNB=48; Fig 1). In PSW multivariable Cox regression analyses, SLNB-based RT was an independent predictor of both BCR (HR 0.38, 95% CI 0.25-0.59, P <0.001) and RR (HR 0.44, 95% CI 0.28-0.69, P <0.001). CONCLUSIONS: SLNB-guided RT is associated with a decreased risk of BCR and RR when compared to prostate-only RT in cN0 PCa patients. These results suggest an important role for SLNB in selecting cN0 PCa patients that might profit from WPRT and ADT intensification, and justify a prospective comparison. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e402 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hilda de Barros More articles by this author Nikolaos Grivas More articles by this author Jan Duin More articles by this author Daan Mulder More articles by this author Vincent van der Noort More articles by this author Arjen Noordzij More articles by this author Esther Wit More articles by this author Eva Schaake More articles by this author Pim van Leeuwen More articles by this author Henk van der Poel More articles by this author Expand All Advertisement PDF DownloadLoading ...

Purpose. We propose a neural network for fast prediction of realistic, time-parametrized deformations between pairs of input segmentations. The proposed method was used to generate a library of planning CTVs for cervical cancer radiotherapy.Methods.A 3D convolutional neural network (CNN) was introduced to predict a stationary velocity field given the distance maps of the cervix CTV in empty and full bladder anatomy. Diffeomorphic deformation trajectories between the two states were obtained by time integration. Intermediate deformation states were used to populate a library of cervix CTVs. The network was trained on cervix CTV deformations of 20 patients generated by finite element modeling (FEM). Validation was performed on FEM data of 9 healthy volunteers. Additionally, for these subjects, CTV deformations were observed in a series of repeat MR scans as the bladder filled from empty to full. Predicted and FEM libraries were compared, and benchmarked against the observed deformations. Finally, for an independent test set of 20 patients the predicted libraries were evaluated clinically, and compared to the current method.Results.The median Dice score over the validation subjects between the predicted and FEM libraries was >0.95 throughout the deformation, with a median 90 percentile surface distance of <3 mm. The ability to cover observed CTVs was similar for both the FEM-based and the proposed method, with residual offsets being about twice as large as the difference between the two methods. Clinical evaluation showed improved library properties over the method currently used in clinic.Conclusions.We proposed a CNN trained on FEM deformations, which predicts the deformation trajectory between two input states of the cervix CTV in one forward pass. We applied this to CTV library prediction for cervical cancer. The network is able to mimic FEM deformations well, while being much faster and simpler in use.

Background and Purpose: Magnetic resonance (MR) guided radiotherapy utilizes MR images for (online) plan adaptation and image guidance. The aim of this study was to investigate the impact of variation in MR acquisition time and scan resolution on image quality, interobserver variation in contouring and intembserver variation in registration. Materials and Methods: Nine patients with prostate cancer were included. Four T2-weighted 3D turbo spin echo (T2w 3D TSE) sequences were acquired with different acquisition times and resolutions. Two radiologists assessed image quality, conspicuity of the capsule, peripheral zone and central gland architecture and motion artefacts on a 5 point scale. Images were delineated by two radiation oncologists and interobserver variation was assessed by the 95% Hausdorff distance. Seven observers registered the MR images on the planning CT. Registrations were compared on systematic offset and interobserver variation. Results: Acquisition times ranged between 1.3 and 6.3 min. Overall image quality and capsule definition were significantly worse for the MR sequence with an acquisition time of 1.3 min compared to the other sequences. Median 95% Hausdorff distance showed no significant differences in interobserver variation of contouring. Systematic offset and interobserver variation in registration were small (<1 mm) and of no clinical significance. Conclusions: Our results can be used to effectively shorten overall fraction time for online adaptive MR guided radiotherapy by optimising the imaging sequence used for registration. From the sequences studied, a sequence of 3.1 min with anisotropic voxels of 1.2 x 1.2 x 2.4 mm(3) provided the shortest acquisition time without compromising image quality.

Objectives To examine the anatomical distribution of prostate cancer (PCa) recurrence on gallium‐68 prostate‐specific membrane antigen ( 68 Ga‐PSMA) positron‐emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after undergoing radical prostatectomy (RP) with pathological lymph node metastasis (pN1) in their extended pelvic lymph node dissection (ePLND), and to compare the location of PCa recurrence with the location of the initial lymph node metastasis at ePLND. Materials and Methods We retrospectively reviewed 100 patients with BCR (PSA 0.05–5.00 ng/mL) after RP with pN1 ePLND who underwent 68 Ga‐PSMA PET/CT to guide salvage therapy. Clinical and pathological features and anatomical locations of PCa recurrence on 68 Ga‐PSMA PET/CT were obtained, and management impact was recorded. Results In all, 68 patients (68%) had a positive and 32 patients (32%) had a negative 68 Ga‐PSMA PET/CT result. Of the 68 patients with a positive 68 Ga‐PSMA PET/CT, 44 (65%) showed abnormal uptake only in the pelvic area, seven (10%) only outside the pelvic area, and 17 (25%) both within and outside the pelvic area. 68 Ga‐PSMA PET/CT‐positive pelvic lymph nodes were often (84%) detected on the same side as the lymph node metastasis diagnosed at ePLND. Based on the outcomes of the 68 Ga‐PSMA PET/CT, change of management was noted in 68% of the patients. Conclusion Recurrence of PCa on 68 Ga‐PSMA PET/CT was limited to the pelvis in the majority of patients with BCR after RP with pN1 ePLND. Moreover, recurrence was often detected on the same side as the lymph node metastasis at ePLND. The results confirm the diagnostic value of 68 Ga‐PSMA PET/CT in patients with BCR after RP with pN1 ePLND. Prospective studies are needed to support the long‐term benefit of 68 Ga‐PSMA PET/CT‐dictated management changes.

Abstract Objectives To determine the consensus of a Dutch multidisciplinary expert panel on the diagnostic evaluation and treatment of de novo and recurrent metastatic prostate cancer (PCa) limited to non‐regional lymph nodes (M1a) in daily clinical practice. Materials and methods The panel consisted of 37 Dutch specialists from disciplines involved in the management of M1a PCa (urology, medical and radiation oncology, radiology, and nuclear medicine). We used a modified Delphi method consisting of two voting rounds and a consensus meeting (video conference). Consensus (good agreement) was defined as the situation in which ≥ 75% of the panelists chose the same option. Results Consensus existed for 57% of the items. The panel agreed that prostate‐specific membrane antigen positron emission tomography/computed tomography (PSMA‐PET/CT) is the most appropriate standard imaging modality to identify de novo (100%) and recurrent (97%) M1a PCa. Androgen deprivation therapy (ADT) combined with radiotherapy to the prostate ± the M1a lesion(s) was most frequently considered an option for de novo M1a PCa. For M1a as recurrent disease, ADT alone, deferring treatment, or local radiotherapy to the M1a lesion(s) were judged to be the most important treatment options. However, no specific indications for treatment choice in relation to disease characteristics could be formulated. Conclusions The Dutch consensus panel preferred PSMA‐PET/CT as the standard diagnostic modality to detect M1a PCa. Although potential treatment options were identified, explicit recommendations could not be formulated. This might (partly) be explained by the absence of high‐level clinical evidence in this subset of patients. Further research is, therefore, strongly encouraged.

Background and purpose Radiation dose escalation using hypofractionation might improve overall survival (OS). We investigated OS in a phase II multicenter study in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with hypofractionated concurrent chemoradiotherapy. Materials and methods A 2-armed phase II, multi-center study (NTR2230) was performed with the aim to assess the effect of cetuximab to concurrent chemoradiotherapy in LA-NSCLC patients (stage II/IIIA/B). Arm A received high dose radiotherapy (24×2.75Gy) and concurrent daily low-dose cisplatin (6mg/m2). Arm B received an identical treatment regimen with additional weekly cetuximab. Kaplan–Meier survival curves and 1-, 2- and 5-year OS proportions were calculated. Results Between February 2009 and May 2011, 102 patients were randomly allocated in two arms. Median OS was 31.5months (range 12.8–52.3), not significantly different between arms A and B; 33.0 (range 17.0–57.0) and 30.0 (11.0–52.0) months. 1-, 2- and 5-year OS rates were 74.5%, 59.4% and 37.3%, respectively. In multivariate analyses, worse performance score, V35 of the esophagus and the existence of comorbidities were significantly (P-value<0.05) associated with a shorter OS. Discussion In this phase II trial, the median OS for the entire group was remarkably high; 31.5months. Furthermore, 5-year OS was still 37.3%. Hypofractionation might contribute to improved OS in LA-NSCLC patients.

BACKGROUND AND PURPOSE:Conebeam-CT (CBCT) guidance is often used for setup verification of lung cancer patients treated with radiotherapy. The purpose of this study was to quantify intra-thoracic anatomical changes (ITACs) during the radiotherapy treatment and to hand over a decision support system to guide the radiation therapy technologist and radiation oncologist in prioritizing these changes.MATERIALS AND METHODS:1793 CBCT-scans of 177 lung cancer patients treated in 2010 in our institute with radical radiotherapy were evaluated. Our decision support system: "the Traffic Light Protocol", was retrospectively applied to these CBCT-scans. The protocol has four levels: red (immediate action before treatment), orange (action before next fraction), yellow (no action required) and green (no change).RESULTS:In 128 patients (72%), 210 ITACs were observed with a maximum level of red, orange and yellow in 12%, 36% and 24% respectively. Types of observed ITACs were, tumor regression (35%), tumor baseline shift (27%), changes in atelectasis (19%), tumor progression (10%), pleural effusion (6%) and infiltrative changes (3%).CONCLUSIONS:ITACs have been observed in 72% of all lung cancer patients during the course of radical radiotherapy. The clinical relevance of the proposed ITAC classification in lung radiotherapy needs to be validated in a prospective analysis.

Abstract Background: Reliable diagnostic tests are needed to identify early stage non-small cell lung carcinoma (NSCLC) patients with poor prognosis. Concomitantly there is a clear need for tests that enable the selection of patients who will benefit from targeted therapy with kinase inhibitors. We evaluated kinase activity profiles in two groups of early stage NSCLC patients, either for prognosis of long- or short-term survival, or for predicting erlotinib drug response. Method: Retrospective studies were performed on fresh frozen resection material of two groups of early stage NSCLC patients. The first group consisted of 48 short- and long-term survivors who underwent a complete surgical resection (5+ years follow-up). The second group consisted of 14 NSCLC patients who received 3 weeks of neo-adjuvant treatment with erlotinib prior to complete surgical resection. Response evaluation to neo-adjuvant treatment was based on histopathological examination of the surgical specimens. For both studies, kinase activity profiles of lysed cryosections of tumour tissues were generated in the presence and absence of protein tyrosine kinase inhibitors on PamChip® peptide micro-arrays, comprising 144 tyrosine containing peptides, derived from known phosphorylation sites of human proteins. Partial least square discriminant analysis was used to construct prediction models. ClustalW alignment algorithms were used to investigate the most informative phosphorylation sites. Results: Kinase activity profiles obtained in the absence of inhibitor did not distinguish between subgroups (long- versus short-term survival, responder or non-responder to TKI), whereas ratios of inhibited versus non-inhibited signals resulted in distinct classifiers predicting survival for the first group, and response for the second group. Multivariate unsupervised analysis with leave-one-out cross-validation resulted in an error rate for survival prediction of 29%. In the drug response prediction 13 out of 14 patients were correctly classified. Conclusion: This is the first study to show that kinase activity profiles of tumour tissue exposed to a kinase inhibitor can be used to identify NSCLC patients likely to respond to erlotinib treatment. Furthermore, based on kinase activity profiles of early stage NSCLC tumours, a prognostic classifier, for a set of 48 patients, was obtained. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4113. doi:10.1158/1538-7445.AM2011-4113